It feels like COVID is closing in

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Changed
Fri, 12/03/2021 - 08:48

Like so many of you, I have weathered COVID-19 for the last almost 2 years. We’ve dealt with anxiety in our patients and ourselves, ever conflicting directives over masks, and uncertainty and hope over vaccinations.

Dr. Elspeth Cameron Ritchie

In the beginning, it seemed elsewhere. Wuhan, China, the state of Washington, New York City.

In the beginning, I awoke with rising anxiety every morning at 4 a.m.

Now, it is part of life. We know how to do this.

I work in a D.C. hospital that takes care of COVID-19 patients. I don’t intubate or come into direct contact with patients’ secretions.

I felt lucky.

Last summer, I felt relief, after being fully vaccinated. We thought we were almost over it. But the numbers abroad and in the United States keep rising.

We have developed protocols. We test every patient for COVID-19 before admitting them to psychiatry, which is now routine. COVID-19–positive patients with suicidal ideation go to our medicine-psychiatric unit. We are single-room occupancy. No visitors.

Now, it feels like COVID is closing in. Lots of my patients on consultation-liaison psychiatry had COVID-19 or do now. The number of patients with long COVID is increasing. My elderly mother-in-law picked it up from a hospital. My young, healthy adult son got it but is now doing relatively OK. We will see if his ADHD worsens.

I received contact tracing recently for going into a patient room with contact precautions. I had put on the gown and gloves, but did I wear my goggles? I keep them on my forehead but could not remember if I had slipped them over my eyes.

I get tested weekly. My nose runs inside my mask. I sneeze. Is this COVID?

Of course, I am vaccinated with a booster shot. But breakthrough infections occur.

I am lucky, I keep reminding myself. I have a job and income and good PPE.

So, we are learning how to manage this disease. But it still closes in. My brain screams: “I do not want to catch this disease. I do not want to get sick. I do not want to get long COVID.”

“Calm down, Cam,” I tell myself. “You can do this!” I have learned how to do all the PPE, including tying the plastic ties along the backs of the plastic gowns.

All psychiatry meetings are virtual now. I cannot do virtual with enthusiasm. I say I will, but then do not log on. I miss the camaraderie.

All appointments are mainly telehealth. That has its pros and cons.

So bottom line – I will keep keeping on.

But I really want others to get vaccinated and wear masks. More than that, how can we as a psychiatric community get us through this pandemic? How can we support each other and our patients?

Here are a few suggestions, some of which I have made before:

  • Focus on what we can control, especially exercise and sleep. Walk during times when the sun is shining. Rake the gorgeous autumn yellow and orange leaves.
  • Give small (or large) gifts of kindness to others. Give to food banks, provide large tips to those who bring you takeout, help out at an animal shelter.
  • Talk through established media about self-care and therapy for anxiety and depression.
  • Clean out your closets. Give clothes to Afghan refugees.
  • Read good books about trying times – such as World War II and the long wars in Afghanistan and Iraq.
  • Take care of veterans and the elderly and homeless.
  • Take care of yourself and your family.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center. She has no conflicts of interest.

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Like so many of you, I have weathered COVID-19 for the last almost 2 years. We’ve dealt with anxiety in our patients and ourselves, ever conflicting directives over masks, and uncertainty and hope over vaccinations.

Dr. Elspeth Cameron Ritchie

In the beginning, it seemed elsewhere. Wuhan, China, the state of Washington, New York City.

In the beginning, I awoke with rising anxiety every morning at 4 a.m.

Now, it is part of life. We know how to do this.

I work in a D.C. hospital that takes care of COVID-19 patients. I don’t intubate or come into direct contact with patients’ secretions.

I felt lucky.

Last summer, I felt relief, after being fully vaccinated. We thought we were almost over it. But the numbers abroad and in the United States keep rising.

We have developed protocols. We test every patient for COVID-19 before admitting them to psychiatry, which is now routine. COVID-19–positive patients with suicidal ideation go to our medicine-psychiatric unit. We are single-room occupancy. No visitors.

Now, it feels like COVID is closing in. Lots of my patients on consultation-liaison psychiatry had COVID-19 or do now. The number of patients with long COVID is increasing. My elderly mother-in-law picked it up from a hospital. My young, healthy adult son got it but is now doing relatively OK. We will see if his ADHD worsens.

I received contact tracing recently for going into a patient room with contact precautions. I had put on the gown and gloves, but did I wear my goggles? I keep them on my forehead but could not remember if I had slipped them over my eyes.

I get tested weekly. My nose runs inside my mask. I sneeze. Is this COVID?

Of course, I am vaccinated with a booster shot. But breakthrough infections occur.

I am lucky, I keep reminding myself. I have a job and income and good PPE.

So, we are learning how to manage this disease. But it still closes in. My brain screams: “I do not want to catch this disease. I do not want to get sick. I do not want to get long COVID.”

“Calm down, Cam,” I tell myself. “You can do this!” I have learned how to do all the PPE, including tying the plastic ties along the backs of the plastic gowns.

All psychiatry meetings are virtual now. I cannot do virtual with enthusiasm. I say I will, but then do not log on. I miss the camaraderie.

All appointments are mainly telehealth. That has its pros and cons.

So bottom line – I will keep keeping on.

But I really want others to get vaccinated and wear masks. More than that, how can we as a psychiatric community get us through this pandemic? How can we support each other and our patients?

Here are a few suggestions, some of which I have made before:

  • Focus on what we can control, especially exercise and sleep. Walk during times when the sun is shining. Rake the gorgeous autumn yellow and orange leaves.
  • Give small (or large) gifts of kindness to others. Give to food banks, provide large tips to those who bring you takeout, help out at an animal shelter.
  • Talk through established media about self-care and therapy for anxiety and depression.
  • Clean out your closets. Give clothes to Afghan refugees.
  • Read good books about trying times – such as World War II and the long wars in Afghanistan and Iraq.
  • Take care of veterans and the elderly and homeless.
  • Take care of yourself and your family.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center. She has no conflicts of interest.

Like so many of you, I have weathered COVID-19 for the last almost 2 years. We’ve dealt with anxiety in our patients and ourselves, ever conflicting directives over masks, and uncertainty and hope over vaccinations.

Dr. Elspeth Cameron Ritchie

In the beginning, it seemed elsewhere. Wuhan, China, the state of Washington, New York City.

In the beginning, I awoke with rising anxiety every morning at 4 a.m.

Now, it is part of life. We know how to do this.

I work in a D.C. hospital that takes care of COVID-19 patients. I don’t intubate or come into direct contact with patients’ secretions.

I felt lucky.

Last summer, I felt relief, after being fully vaccinated. We thought we were almost over it. But the numbers abroad and in the United States keep rising.

We have developed protocols. We test every patient for COVID-19 before admitting them to psychiatry, which is now routine. COVID-19–positive patients with suicidal ideation go to our medicine-psychiatric unit. We are single-room occupancy. No visitors.

Now, it feels like COVID is closing in. Lots of my patients on consultation-liaison psychiatry had COVID-19 or do now. The number of patients with long COVID is increasing. My elderly mother-in-law picked it up from a hospital. My young, healthy adult son got it but is now doing relatively OK. We will see if his ADHD worsens.

I received contact tracing recently for going into a patient room with contact precautions. I had put on the gown and gloves, but did I wear my goggles? I keep them on my forehead but could not remember if I had slipped them over my eyes.

I get tested weekly. My nose runs inside my mask. I sneeze. Is this COVID?

Of course, I am vaccinated with a booster shot. But breakthrough infections occur.

I am lucky, I keep reminding myself. I have a job and income and good PPE.

So, we are learning how to manage this disease. But it still closes in. My brain screams: “I do not want to catch this disease. I do not want to get sick. I do not want to get long COVID.”

“Calm down, Cam,” I tell myself. “You can do this!” I have learned how to do all the PPE, including tying the plastic ties along the backs of the plastic gowns.

All psychiatry meetings are virtual now. I cannot do virtual with enthusiasm. I say I will, but then do not log on. I miss the camaraderie.

All appointments are mainly telehealth. That has its pros and cons.

So bottom line – I will keep keeping on.

But I really want others to get vaccinated and wear masks. More than that, how can we as a psychiatric community get us through this pandemic? How can we support each other and our patients?

Here are a few suggestions, some of which I have made before:

  • Focus on what we can control, especially exercise and sleep. Walk during times when the sun is shining. Rake the gorgeous autumn yellow and orange leaves.
  • Give small (or large) gifts of kindness to others. Give to food banks, provide large tips to those who bring you takeout, help out at an animal shelter.
  • Talk through established media about self-care and therapy for anxiety and depression.
  • Clean out your closets. Give clothes to Afghan refugees.
  • Read good books about trying times – such as World War II and the long wars in Afghanistan and Iraq.
  • Take care of veterans and the elderly and homeless.
  • Take care of yourself and your family.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center. She has no conflicts of interest.

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COVID-19 and the immunocompromised physician

Article Type
Changed
Thu, 12/02/2021 - 16:41

Working feverishly to complete the myriad patient notes accumulated throughout a hectic day, my phone vibrated – alerting me to a number that, over the past several years, has wrought uncertainty, grief, and overwhelming relief. Answering hesitantly, I listened to my physician’s pharmacist inform me of unexpected and alarming news.

Dr. Tanya Thomas

Since COVID-19 was first identified more than 1 year ago, more than 770,000 people have died in the United States. In the wake of those losses, countless grieve while attempting to navigate a future without their loved ones. Meanwhile, scientists worked feverishly to combat a pandemic relentless in contagion. As health care professionals, we work tirelessly against the sharpened scythe of death, toiling day after day without an identifiable end. All the while, advocacy has prevailed as the need for personal protective equipment, improved ventilation systems, sanitization measures, and other mitigation measures, such as mask wearing and social distancing, echoed swiftly across the nation and around the world.

But, as the months have progressed, and life has seemingly transitioned toward a parallel version of reality, subsections of communities have grown restless. Several nontherapeutic, ineffective, and falsely touted regimens have been promoted. Amid the chaos of misinformation, most medical professionals have sought support from respected journals and infectious disease experts to filter out jargon and piece together scientifically sound protocols. Although many lives have prevailed by way of those advancements, mixed messages about interventions have emerged – and in many quarters across the country, anger, resistance, and outright refusal have prevailed.

Yet, we – the medical community – have forged ever onward as the cases continued and the death toll steadily climbed. In many cases, physicians who are years removed from critical care training have been thrust into COVID units, while residents have shifted toward working outside of their chosen specialty. Outpatient offices have closed, salaries have been cut, and furloughs have loomed as days fade into months. Beset with exhaustion and uncertainty, sacrifice has become a common thread that intrinsically united us against an unrelenting foe.

Most people continued navigating the many changes and made concerted efforts to mimic our prepandemic lives. Working from home in makeshift offices, dusting off math skills to assist children through the doldrums of distance learning, and mastering various audiovisual platforms, we reinforced social bonds and forged new connections echoing the hallmark resilience reminiscent of our shared distant ancestry.

As of this writing, thanks to our work – and that of scientists and policy makers – about 69% of Americans have received at least one dose of vaccine, and vaccines are widely available to children 5 and older. But it has been disheartening to watch misinformation about vaccine research and development propagated by political figures, social media, and lay people.
 

Processing the phone call

While listening to my physician’s pharmacist, I slowed my breaths in an effort to find calm. Years of navigating the American health care industry had left me both equipped and ill-prepared for the unexpected. I listened intently to the pharmacist’s words while staring blankly at a computer screen – uncertain of what had felt so assured not 10 minutes earlier.

That’s when I got the news. The intravenous medication that aided in my stabilization had suffered a critical shortage because of its successful use in the treatment of patients with COVID-19 pneumonia – patients who, in a majority of cases, had likely refused the vaccines. As result, the medication that had enabled my return to work, active engagement in nonwork pursuits, and most importantly, equipped my body to thrive despite the damage it had suffered, suddenly vanished.

Gently placing my phone on the desk, my heart beat rapidly as tears steadily streamed down my face. Staring blankly ahead, my hands gradually balled into fists as I let out a sound of fear, agony, and uncertainty. Screaming at everything and nothing, nausea swelled as panic flooded my body. In that moment, I ruminated on the conversation with the pharmacist. There had been no discussion, no option for me to maintain accessibility to this valuable medicine. Consequently, I felt helpless. Although the same medication, albeit a different mechanism of delivery, was promptly chosen as an adequate substitute, there was no guarantee of it bestowing the same degree of efficacy. So I was terrified, envisioning the progress made over several years as plummeting into an abyss of pain and despair. What are those of us who have chosen medicine as our profession but are immunocompromised expected to make of this?

Over the next several weeks, I diligently adhered to the new regimen and focused on positive mentation. Nevertheless, day by day, the symptoms worsened; eventually, I became bed ridden. I tried to gather what little composure remained to reschedule patients and justify the resounding guilt of perceived failure. I remember the sweet and gentle look of my child as I once again could not summon the strength to play pretend. This felt overwhelming. Would I ever go back to work? Would I see my child grow? No amount of pleading or screaming would change the fact that a medical system chose to roll the dice on my health. In a haze of discomfort and betrayal, I wondered how a physician or medical facility could justify removing medication from someone reliant upon it. How do we choose the appropriate allocation of resources when the consequences are potentially catastrophic?
 

Searching for context

When a country is founded on the mission of rising as a leading world power built upon the concepts of freedom, basic human rights, and individuality while supporting an infrastructure of capitalism, power, and control, crises – particularly those related to public health – can fan deep divisions. Here in the United States, we have seen misinterpretation, misunderstanding, and bitter indignation fuel the flames of provocation as protests of mask mandates, distance learning, and social distancing were touted as violating the very core upon which the country was established. Frustration, palpable among health care professionals, grew ever greater as the importance of vaccination in quelling virus mutations and decreasing morbidity and mortality were openly disparaged and ignored.

Not only have we watched people refuse the vaccines, but some are ignoring other mitigation measures. So the question becomes: How are we, as health care professionals trying to maintain a therapeutic alliance with those who reject lifesaving practices, expected to process this? Sitting in appointments and attempting interventions without judgment feels impractical and nearly impossible – particularly when the behaviors of these patients have the potential of violating our own health and well-being. How do we remain altruistic in our endeavors when those who seek our care seem callously indifferent to our lives – and to those of our families?
 

 

 

Measuring the value of life

Within the fevered haze of this past year, many stories highlighting grim realities have captured the media spotlight. From individuals unable to have emergency evaluations because of facilities being inundated by COVID-19 patients to individuals prematurely discharged, hospital bed shortages, and financial pressures from insurance companies. In reciting the phrase “Primum non noncere,” we physicians are committing to providing fair and competent medical treatment. At times, urgent decisions are necessary but are always made in the best interest of the patient(s). Ultimately, I am left debating how these agonizing weeks served any meaningful purpose. Moreover, when choosing the many over the few, what are the determinant factors? I am left asking: What is the value of a life?

Philosophically, this ethical dilemma is captured succinctly via the “trolley problem,” formulated in 1967 by Philippa Foot, MD. This is how Dr. Foot’s formulation unfolds: Close your eyes, and imagine you are inside a trolley careening unhindered down the rumbling tracks. Straight ahead you see five people bound to the tracks in imminent danger of being struck, and on the other side, one person is tied to the tracks. Do you continue the same course – thereby condemning five innocent people to death – or do you make the active decision to switch tracks, therefore consigning the one to their fate? Envision the people what do they look like? How old are they? If the one were a small child or a close friend, would that alter your decision? How does one make such a harrowing choice knowing the irreversible consequences? Depending on your action, this quandary falls within two primary schools of thought: Utilitarianism, which posits that the best action is the greatest good for the greatest number of people, and deontologicalism, which suggests that action is inherently right or wrong regardless of the consequences. Therefore, the decision to save the five is not favored.

However simplistic those scenarios may read, such principles when viewed through different lenses, they form the basis of medical ethics. In effect, every acute decision, every aspect of treatment is predicated upon the principles of nonmaleficence, beneficence, utility, distributive justice, and autonomy. Yet, the manner in which they are applied is highly contingent upon myriad variables. For example, sociopolitical factors, including population size (rural versus urban), economics (impoverished versus wealthy), as well as demographic factors (age, ethnicity, gender, sexuality) can highly influence and sometimes unknowingly influence interpretation and allocation of health care resources. This dilemma does not yield easily applicable and universal solutions. Nevertheless, it is paramount to evaluate policies effectively and tediously, particularly those with detrimental ramifications. Likewise, remaining flexible in our willingness to explore alternative solutions and encourage open discord among those with opposing viewpoints is key to instituting individual or institutional change that values the one as it values the many.

After several weeks of acute illness and a variety of short-acting interventions, I received approval to resume intravenous therapy. While the saga has ultimately reached a satisfactory conclusion, I am left with stupefied disbelief toward the people who took a gamble on my health. I am facing a battle between understanding the obligation of medicine to provide ethical and reasonable care without hesitation or judgment versus embittered resentment when faced with those who openly campaign against lifesaving interventions, such as the COVID-19 vaccine. For me, each day and the one that follows is riddled with complicated emotion. Every time I prematurely cease activity out of discomfort and weariness, I worry about my increasingly foreboding workload. In those moments, in that place of questions without answers, I remember that someone somewhere ultimately decided to switch the trolley’s track.

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

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Working feverishly to complete the myriad patient notes accumulated throughout a hectic day, my phone vibrated – alerting me to a number that, over the past several years, has wrought uncertainty, grief, and overwhelming relief. Answering hesitantly, I listened to my physician’s pharmacist inform me of unexpected and alarming news.

Dr. Tanya Thomas

Since COVID-19 was first identified more than 1 year ago, more than 770,000 people have died in the United States. In the wake of those losses, countless grieve while attempting to navigate a future without their loved ones. Meanwhile, scientists worked feverishly to combat a pandemic relentless in contagion. As health care professionals, we work tirelessly against the sharpened scythe of death, toiling day after day without an identifiable end. All the while, advocacy has prevailed as the need for personal protective equipment, improved ventilation systems, sanitization measures, and other mitigation measures, such as mask wearing and social distancing, echoed swiftly across the nation and around the world.

But, as the months have progressed, and life has seemingly transitioned toward a parallel version of reality, subsections of communities have grown restless. Several nontherapeutic, ineffective, and falsely touted regimens have been promoted. Amid the chaos of misinformation, most medical professionals have sought support from respected journals and infectious disease experts to filter out jargon and piece together scientifically sound protocols. Although many lives have prevailed by way of those advancements, mixed messages about interventions have emerged – and in many quarters across the country, anger, resistance, and outright refusal have prevailed.

Yet, we – the medical community – have forged ever onward as the cases continued and the death toll steadily climbed. In many cases, physicians who are years removed from critical care training have been thrust into COVID units, while residents have shifted toward working outside of their chosen specialty. Outpatient offices have closed, salaries have been cut, and furloughs have loomed as days fade into months. Beset with exhaustion and uncertainty, sacrifice has become a common thread that intrinsically united us against an unrelenting foe.

Most people continued navigating the many changes and made concerted efforts to mimic our prepandemic lives. Working from home in makeshift offices, dusting off math skills to assist children through the doldrums of distance learning, and mastering various audiovisual platforms, we reinforced social bonds and forged new connections echoing the hallmark resilience reminiscent of our shared distant ancestry.

As of this writing, thanks to our work – and that of scientists and policy makers – about 69% of Americans have received at least one dose of vaccine, and vaccines are widely available to children 5 and older. But it has been disheartening to watch misinformation about vaccine research and development propagated by political figures, social media, and lay people.
 

Processing the phone call

While listening to my physician’s pharmacist, I slowed my breaths in an effort to find calm. Years of navigating the American health care industry had left me both equipped and ill-prepared for the unexpected. I listened intently to the pharmacist’s words while staring blankly at a computer screen – uncertain of what had felt so assured not 10 minutes earlier.

That’s when I got the news. The intravenous medication that aided in my stabilization had suffered a critical shortage because of its successful use in the treatment of patients with COVID-19 pneumonia – patients who, in a majority of cases, had likely refused the vaccines. As result, the medication that had enabled my return to work, active engagement in nonwork pursuits, and most importantly, equipped my body to thrive despite the damage it had suffered, suddenly vanished.

Gently placing my phone on the desk, my heart beat rapidly as tears steadily streamed down my face. Staring blankly ahead, my hands gradually balled into fists as I let out a sound of fear, agony, and uncertainty. Screaming at everything and nothing, nausea swelled as panic flooded my body. In that moment, I ruminated on the conversation with the pharmacist. There had been no discussion, no option for me to maintain accessibility to this valuable medicine. Consequently, I felt helpless. Although the same medication, albeit a different mechanism of delivery, was promptly chosen as an adequate substitute, there was no guarantee of it bestowing the same degree of efficacy. So I was terrified, envisioning the progress made over several years as plummeting into an abyss of pain and despair. What are those of us who have chosen medicine as our profession but are immunocompromised expected to make of this?

Over the next several weeks, I diligently adhered to the new regimen and focused on positive mentation. Nevertheless, day by day, the symptoms worsened; eventually, I became bed ridden. I tried to gather what little composure remained to reschedule patients and justify the resounding guilt of perceived failure. I remember the sweet and gentle look of my child as I once again could not summon the strength to play pretend. This felt overwhelming. Would I ever go back to work? Would I see my child grow? No amount of pleading or screaming would change the fact that a medical system chose to roll the dice on my health. In a haze of discomfort and betrayal, I wondered how a physician or medical facility could justify removing medication from someone reliant upon it. How do we choose the appropriate allocation of resources when the consequences are potentially catastrophic?
 

Searching for context

When a country is founded on the mission of rising as a leading world power built upon the concepts of freedom, basic human rights, and individuality while supporting an infrastructure of capitalism, power, and control, crises – particularly those related to public health – can fan deep divisions. Here in the United States, we have seen misinterpretation, misunderstanding, and bitter indignation fuel the flames of provocation as protests of mask mandates, distance learning, and social distancing were touted as violating the very core upon which the country was established. Frustration, palpable among health care professionals, grew ever greater as the importance of vaccination in quelling virus mutations and decreasing morbidity and mortality were openly disparaged and ignored.

Not only have we watched people refuse the vaccines, but some are ignoring other mitigation measures. So the question becomes: How are we, as health care professionals trying to maintain a therapeutic alliance with those who reject lifesaving practices, expected to process this? Sitting in appointments and attempting interventions without judgment feels impractical and nearly impossible – particularly when the behaviors of these patients have the potential of violating our own health and well-being. How do we remain altruistic in our endeavors when those who seek our care seem callously indifferent to our lives – and to those of our families?
 

 

 

Measuring the value of life

Within the fevered haze of this past year, many stories highlighting grim realities have captured the media spotlight. From individuals unable to have emergency evaluations because of facilities being inundated by COVID-19 patients to individuals prematurely discharged, hospital bed shortages, and financial pressures from insurance companies. In reciting the phrase “Primum non noncere,” we physicians are committing to providing fair and competent medical treatment. At times, urgent decisions are necessary but are always made in the best interest of the patient(s). Ultimately, I am left debating how these agonizing weeks served any meaningful purpose. Moreover, when choosing the many over the few, what are the determinant factors? I am left asking: What is the value of a life?

Philosophically, this ethical dilemma is captured succinctly via the “trolley problem,” formulated in 1967 by Philippa Foot, MD. This is how Dr. Foot’s formulation unfolds: Close your eyes, and imagine you are inside a trolley careening unhindered down the rumbling tracks. Straight ahead you see five people bound to the tracks in imminent danger of being struck, and on the other side, one person is tied to the tracks. Do you continue the same course – thereby condemning five innocent people to death – or do you make the active decision to switch tracks, therefore consigning the one to their fate? Envision the people what do they look like? How old are they? If the one were a small child or a close friend, would that alter your decision? How does one make such a harrowing choice knowing the irreversible consequences? Depending on your action, this quandary falls within two primary schools of thought: Utilitarianism, which posits that the best action is the greatest good for the greatest number of people, and deontologicalism, which suggests that action is inherently right or wrong regardless of the consequences. Therefore, the decision to save the five is not favored.

However simplistic those scenarios may read, such principles when viewed through different lenses, they form the basis of medical ethics. In effect, every acute decision, every aspect of treatment is predicated upon the principles of nonmaleficence, beneficence, utility, distributive justice, and autonomy. Yet, the manner in which they are applied is highly contingent upon myriad variables. For example, sociopolitical factors, including population size (rural versus urban), economics (impoverished versus wealthy), as well as demographic factors (age, ethnicity, gender, sexuality) can highly influence and sometimes unknowingly influence interpretation and allocation of health care resources. This dilemma does not yield easily applicable and universal solutions. Nevertheless, it is paramount to evaluate policies effectively and tediously, particularly those with detrimental ramifications. Likewise, remaining flexible in our willingness to explore alternative solutions and encourage open discord among those with opposing viewpoints is key to instituting individual or institutional change that values the one as it values the many.

After several weeks of acute illness and a variety of short-acting interventions, I received approval to resume intravenous therapy. While the saga has ultimately reached a satisfactory conclusion, I am left with stupefied disbelief toward the people who took a gamble on my health. I am facing a battle between understanding the obligation of medicine to provide ethical and reasonable care without hesitation or judgment versus embittered resentment when faced with those who openly campaign against lifesaving interventions, such as the COVID-19 vaccine. For me, each day and the one that follows is riddled with complicated emotion. Every time I prematurely cease activity out of discomfort and weariness, I worry about my increasingly foreboding workload. In those moments, in that place of questions without answers, I remember that someone somewhere ultimately decided to switch the trolley’s track.

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

Working feverishly to complete the myriad patient notes accumulated throughout a hectic day, my phone vibrated – alerting me to a number that, over the past several years, has wrought uncertainty, grief, and overwhelming relief. Answering hesitantly, I listened to my physician’s pharmacist inform me of unexpected and alarming news.

Dr. Tanya Thomas

Since COVID-19 was first identified more than 1 year ago, more than 770,000 people have died in the United States. In the wake of those losses, countless grieve while attempting to navigate a future without their loved ones. Meanwhile, scientists worked feverishly to combat a pandemic relentless in contagion. As health care professionals, we work tirelessly against the sharpened scythe of death, toiling day after day without an identifiable end. All the while, advocacy has prevailed as the need for personal protective equipment, improved ventilation systems, sanitization measures, and other mitigation measures, such as mask wearing and social distancing, echoed swiftly across the nation and around the world.

But, as the months have progressed, and life has seemingly transitioned toward a parallel version of reality, subsections of communities have grown restless. Several nontherapeutic, ineffective, and falsely touted regimens have been promoted. Amid the chaos of misinformation, most medical professionals have sought support from respected journals and infectious disease experts to filter out jargon and piece together scientifically sound protocols. Although many lives have prevailed by way of those advancements, mixed messages about interventions have emerged – and in many quarters across the country, anger, resistance, and outright refusal have prevailed.

Yet, we – the medical community – have forged ever onward as the cases continued and the death toll steadily climbed. In many cases, physicians who are years removed from critical care training have been thrust into COVID units, while residents have shifted toward working outside of their chosen specialty. Outpatient offices have closed, salaries have been cut, and furloughs have loomed as days fade into months. Beset with exhaustion and uncertainty, sacrifice has become a common thread that intrinsically united us against an unrelenting foe.

Most people continued navigating the many changes and made concerted efforts to mimic our prepandemic lives. Working from home in makeshift offices, dusting off math skills to assist children through the doldrums of distance learning, and mastering various audiovisual platforms, we reinforced social bonds and forged new connections echoing the hallmark resilience reminiscent of our shared distant ancestry.

As of this writing, thanks to our work – and that of scientists and policy makers – about 69% of Americans have received at least one dose of vaccine, and vaccines are widely available to children 5 and older. But it has been disheartening to watch misinformation about vaccine research and development propagated by political figures, social media, and lay people.
 

Processing the phone call

While listening to my physician’s pharmacist, I slowed my breaths in an effort to find calm. Years of navigating the American health care industry had left me both equipped and ill-prepared for the unexpected. I listened intently to the pharmacist’s words while staring blankly at a computer screen – uncertain of what had felt so assured not 10 minutes earlier.

That’s when I got the news. The intravenous medication that aided in my stabilization had suffered a critical shortage because of its successful use in the treatment of patients with COVID-19 pneumonia – patients who, in a majority of cases, had likely refused the vaccines. As result, the medication that had enabled my return to work, active engagement in nonwork pursuits, and most importantly, equipped my body to thrive despite the damage it had suffered, suddenly vanished.

Gently placing my phone on the desk, my heart beat rapidly as tears steadily streamed down my face. Staring blankly ahead, my hands gradually balled into fists as I let out a sound of fear, agony, and uncertainty. Screaming at everything and nothing, nausea swelled as panic flooded my body. In that moment, I ruminated on the conversation with the pharmacist. There had been no discussion, no option for me to maintain accessibility to this valuable medicine. Consequently, I felt helpless. Although the same medication, albeit a different mechanism of delivery, was promptly chosen as an adequate substitute, there was no guarantee of it bestowing the same degree of efficacy. So I was terrified, envisioning the progress made over several years as plummeting into an abyss of pain and despair. What are those of us who have chosen medicine as our profession but are immunocompromised expected to make of this?

Over the next several weeks, I diligently adhered to the new regimen and focused on positive mentation. Nevertheless, day by day, the symptoms worsened; eventually, I became bed ridden. I tried to gather what little composure remained to reschedule patients and justify the resounding guilt of perceived failure. I remember the sweet and gentle look of my child as I once again could not summon the strength to play pretend. This felt overwhelming. Would I ever go back to work? Would I see my child grow? No amount of pleading or screaming would change the fact that a medical system chose to roll the dice on my health. In a haze of discomfort and betrayal, I wondered how a physician or medical facility could justify removing medication from someone reliant upon it. How do we choose the appropriate allocation of resources when the consequences are potentially catastrophic?
 

Searching for context

When a country is founded on the mission of rising as a leading world power built upon the concepts of freedom, basic human rights, and individuality while supporting an infrastructure of capitalism, power, and control, crises – particularly those related to public health – can fan deep divisions. Here in the United States, we have seen misinterpretation, misunderstanding, and bitter indignation fuel the flames of provocation as protests of mask mandates, distance learning, and social distancing were touted as violating the very core upon which the country was established. Frustration, palpable among health care professionals, grew ever greater as the importance of vaccination in quelling virus mutations and decreasing morbidity and mortality were openly disparaged and ignored.

Not only have we watched people refuse the vaccines, but some are ignoring other mitigation measures. So the question becomes: How are we, as health care professionals trying to maintain a therapeutic alliance with those who reject lifesaving practices, expected to process this? Sitting in appointments and attempting interventions without judgment feels impractical and nearly impossible – particularly when the behaviors of these patients have the potential of violating our own health and well-being. How do we remain altruistic in our endeavors when those who seek our care seem callously indifferent to our lives – and to those of our families?
 

 

 

Measuring the value of life

Within the fevered haze of this past year, many stories highlighting grim realities have captured the media spotlight. From individuals unable to have emergency evaluations because of facilities being inundated by COVID-19 patients to individuals prematurely discharged, hospital bed shortages, and financial pressures from insurance companies. In reciting the phrase “Primum non noncere,” we physicians are committing to providing fair and competent medical treatment. At times, urgent decisions are necessary but are always made in the best interest of the patient(s). Ultimately, I am left debating how these agonizing weeks served any meaningful purpose. Moreover, when choosing the many over the few, what are the determinant factors? I am left asking: What is the value of a life?

Philosophically, this ethical dilemma is captured succinctly via the “trolley problem,” formulated in 1967 by Philippa Foot, MD. This is how Dr. Foot’s formulation unfolds: Close your eyes, and imagine you are inside a trolley careening unhindered down the rumbling tracks. Straight ahead you see five people bound to the tracks in imminent danger of being struck, and on the other side, one person is tied to the tracks. Do you continue the same course – thereby condemning five innocent people to death – or do you make the active decision to switch tracks, therefore consigning the one to their fate? Envision the people what do they look like? How old are they? If the one were a small child or a close friend, would that alter your decision? How does one make such a harrowing choice knowing the irreversible consequences? Depending on your action, this quandary falls within two primary schools of thought: Utilitarianism, which posits that the best action is the greatest good for the greatest number of people, and deontologicalism, which suggests that action is inherently right or wrong regardless of the consequences. Therefore, the decision to save the five is not favored.

However simplistic those scenarios may read, such principles when viewed through different lenses, they form the basis of medical ethics. In effect, every acute decision, every aspect of treatment is predicated upon the principles of nonmaleficence, beneficence, utility, distributive justice, and autonomy. Yet, the manner in which they are applied is highly contingent upon myriad variables. For example, sociopolitical factors, including population size (rural versus urban), economics (impoverished versus wealthy), as well as demographic factors (age, ethnicity, gender, sexuality) can highly influence and sometimes unknowingly influence interpretation and allocation of health care resources. This dilemma does not yield easily applicable and universal solutions. Nevertheless, it is paramount to evaluate policies effectively and tediously, particularly those with detrimental ramifications. Likewise, remaining flexible in our willingness to explore alternative solutions and encourage open discord among those with opposing viewpoints is key to instituting individual or institutional change that values the one as it values the many.

After several weeks of acute illness and a variety of short-acting interventions, I received approval to resume intravenous therapy. While the saga has ultimately reached a satisfactory conclusion, I am left with stupefied disbelief toward the people who took a gamble on my health. I am facing a battle between understanding the obligation of medicine to provide ethical and reasonable care without hesitation or judgment versus embittered resentment when faced with those who openly campaign against lifesaving interventions, such as the COVID-19 vaccine. For me, each day and the one that follows is riddled with complicated emotion. Every time I prematurely cease activity out of discomfort and weariness, I worry about my increasingly foreboding workload. In those moments, in that place of questions without answers, I remember that someone somewhere ultimately decided to switch the trolley’s track.

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

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Supporting clinician wellbeing and organizational resilience

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Changed
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The COVID-19 pandemic highlighted a major gap in our institutional infrastructure in medicine – specifically, the absence of established policies and programs to support clinician wellbeing and organizational resilience.

Dr. Megan A. Adams

In a 2020 report, the National Academy of Medicine advocated for “fixing the workplace,” rather than “fixing the worker,” as a more sustainable mechanism to advance physician wellbeing and foster organizational resilience. According to the report, “A resilient organization, or one that has matched job demands with job resources for its workers and that has created a culture of connection, transparency, and improvement, is better positioned to achieve organizational objectives during ordinary times and also to weather challenges during times of crisis” (Sinsky CA et al. “Organizational Evidence-Based and Promising Practices for Improving Clinician Well-Being.” National Academy of Medicine. Nov. 2, 2020.

The report highlights six domains of evidence-based practices to support organizational resilience and improve clinician well-being: organizational commitment, workforce assessment (such as measurement of physician wellbeing and burnout); leadership (including shared accountability, distributed leadership, and the emerging role of a chief wellness officer), policy (such as eliminating and/or re-envisioning policies and practices that interfere with clinicians’ ability to provide high-quality patient care), (5) efficiency (such as minimizing administrative tasks to allow clinicians to focus on patient care), and (6) support (such as providing resources and/or policies to support work-life balance, fostering a culture of connection at work). While many organizations (including both academic and community practices) already have begun to invest in this transformation, I urge you to think creatively about whether there is more your practice can do at an organizational level to support and sustain clinician wellbeing and prevent burnout.

In this month’s issue of GIHN, we highlight AGA’s new Clinical Practice Guideline on Coagulation in Cirrhosis, as well as results from a study confirming the benefits of coffee for liver health (welcome news to the caffeine-lovers among us!). We also report on a novel text-based patient-education intervention that aims to connect patients newly diagnosed with colorectal cancer to valuable resources and support.

Thank you for your dedicated readership – we look forward to continuing to bring you engaging, clinically-relevant content in 2022!

Megan A. Adams, MD, JD, MSc
Editor in Chief

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The COVID-19 pandemic highlighted a major gap in our institutional infrastructure in medicine – specifically, the absence of established policies and programs to support clinician wellbeing and organizational resilience.

Dr. Megan A. Adams

In a 2020 report, the National Academy of Medicine advocated for “fixing the workplace,” rather than “fixing the worker,” as a more sustainable mechanism to advance physician wellbeing and foster organizational resilience. According to the report, “A resilient organization, or one that has matched job demands with job resources for its workers and that has created a culture of connection, transparency, and improvement, is better positioned to achieve organizational objectives during ordinary times and also to weather challenges during times of crisis” (Sinsky CA et al. “Organizational Evidence-Based and Promising Practices for Improving Clinician Well-Being.” National Academy of Medicine. Nov. 2, 2020.

The report highlights six domains of evidence-based practices to support organizational resilience and improve clinician well-being: organizational commitment, workforce assessment (such as measurement of physician wellbeing and burnout); leadership (including shared accountability, distributed leadership, and the emerging role of a chief wellness officer), policy (such as eliminating and/or re-envisioning policies and practices that interfere with clinicians’ ability to provide high-quality patient care), (5) efficiency (such as minimizing administrative tasks to allow clinicians to focus on patient care), and (6) support (such as providing resources and/or policies to support work-life balance, fostering a culture of connection at work). While many organizations (including both academic and community practices) already have begun to invest in this transformation, I urge you to think creatively about whether there is more your practice can do at an organizational level to support and sustain clinician wellbeing and prevent burnout.

In this month’s issue of GIHN, we highlight AGA’s new Clinical Practice Guideline on Coagulation in Cirrhosis, as well as results from a study confirming the benefits of coffee for liver health (welcome news to the caffeine-lovers among us!). We also report on a novel text-based patient-education intervention that aims to connect patients newly diagnosed with colorectal cancer to valuable resources and support.

Thank you for your dedicated readership – we look forward to continuing to bring you engaging, clinically-relevant content in 2022!

Megan A. Adams, MD, JD, MSc
Editor in Chief

The COVID-19 pandemic highlighted a major gap in our institutional infrastructure in medicine – specifically, the absence of established policies and programs to support clinician wellbeing and organizational resilience.

Dr. Megan A. Adams

In a 2020 report, the National Academy of Medicine advocated for “fixing the workplace,” rather than “fixing the worker,” as a more sustainable mechanism to advance physician wellbeing and foster organizational resilience. According to the report, “A resilient organization, or one that has matched job demands with job resources for its workers and that has created a culture of connection, transparency, and improvement, is better positioned to achieve organizational objectives during ordinary times and also to weather challenges during times of crisis” (Sinsky CA et al. “Organizational Evidence-Based and Promising Practices for Improving Clinician Well-Being.” National Academy of Medicine. Nov. 2, 2020.

The report highlights six domains of evidence-based practices to support organizational resilience and improve clinician well-being: organizational commitment, workforce assessment (such as measurement of physician wellbeing and burnout); leadership (including shared accountability, distributed leadership, and the emerging role of a chief wellness officer), policy (such as eliminating and/or re-envisioning policies and practices that interfere with clinicians’ ability to provide high-quality patient care), (5) efficiency (such as minimizing administrative tasks to allow clinicians to focus on patient care), and (6) support (such as providing resources and/or policies to support work-life balance, fostering a culture of connection at work). While many organizations (including both academic and community practices) already have begun to invest in this transformation, I urge you to think creatively about whether there is more your practice can do at an organizational level to support and sustain clinician wellbeing and prevent burnout.

In this month’s issue of GIHN, we highlight AGA’s new Clinical Practice Guideline on Coagulation in Cirrhosis, as well as results from a study confirming the benefits of coffee for liver health (welcome news to the caffeine-lovers among us!). We also report on a novel text-based patient-education intervention that aims to connect patients newly diagnosed with colorectal cancer to valuable resources and support.

Thank you for your dedicated readership – we look forward to continuing to bring you engaging, clinically-relevant content in 2022!

Megan A. Adams, MD, JD, MSc
Editor in Chief

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The perils of hubris

Dr. Nasrallah’s fascinating editorial on the psychiatric aspects of prominent individuals’ fall from grace (“From famous to infamous: Psychiatric aspects of the fall from grace,” From the Editor, Current Psychiatry, October 2021, p. 9-10,53) reminded me that the most trenchant insights and antidotes to hubris can more often be found in literature than in a diagnostic code. In Bonfire of the Vanities,1 Tom’s Wolfe’s satire on 1980s New York, self-proclaimed “Master of the Universe” Sherman McCoy lives in a Park Avenue high rise and works as a bond trader “on Wall Street, fifty floors up … overlooking the world!” As quickly becomes apparent, Sherman’s altitude—both literal and figurative—merely serves as a greater distance from which to fall.

Perhaps fittingly, the phenomenon of self-destruction as a byproduct of success was most prominently “diagnosed” by business school professors, not physicians. The propensity for ethical failure at the apex of achievement was coined the “Bathsheba Syndrome,” in reference to the biblical tale of King David’s degenerative sequence of temptation, infidelity, deceit, and treachery while at the height of his power.2 David’s transgressions are enabled by the very success he has achieved.3

One of my valued mentors had an interesting, albeit unscientific, method of mitigating hubris. When he was a senior military lawyer, or judge advocate (JAG), and I was a junior one, my mentor took me to a briefing in which he provided a legal overview to newly minted colonels assuming command billets. One of the functions of JAGs is to provide counsel and advice to commanders. As Dr. Nasrallah noted in his editorial, military leaders are by no means immune from the proverbial fall from grace, and arguably particularly susceptible to it. In beginning his remarks, my mentor offered his heartfelt congratulations to the attendees on their promotion and then proceeded to hand out a pocket mirror for them to pass around. He asked each officer to look in the mirror and personally confirm for him that they were just as unattractive today as they were yesterday.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas



The views expressed in this letter are those of the author and do not necessarily reflect those of any government agency.

1. Wolfe T. Bonfire of the vanities. Farrar, Straus and Giroux; 1987.

2. Ludwig DC, Longenecker CO. The Bathsheba syndrome: the ethical failure of successful leaders. J Bus Ethics. 1993;12:265-273.

3. 2 Samuel 11-12.

 

I enjoyed Dr. Nasrallah’s editorial and his discussion of the dangers of hubris. This brought to mind the role of the auriga in ancient Rome: "the auriga was a slave with gladiator status, whose duty it was to drive a biga, the light vehicle powered by two horses, to transport some important Romans, mainly duces (military commanders). An auriga was a sort of “chauffeur” for important men and was carefully selected from among trustworthy slaves only. It has been supposed also that this name was given to the slave who held a laurel crown, during Roman Triumphs, over the head of the dux, standing at his back but continuously whispering in his ears “Memento Mori” (“remember you are mortal”) to prevent the celebrated commander from losing his sense of proportion in the excesses of the celebrations.”1  

Continue to: Mark S. Komrad, MD...

 

 

Mark S. Komrad, MD

Faculty of Psychiatry

Johns Hopkins Hospital

University of Maryland

Tulane University

Towson, Maryland

Reference

1. Auriga (slave). Accessed November 9, 2021. https://en.wikipedia.org/wiki/Auriga_(slave)

Barriers to care faced by African American patients

According to the US Department of Health and Human Services, the 5 domains of social determinants of health are Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighbor­hood and Built Environment, and Social and Community Context.1 Patients who are African American face many socioeconomic barriers to access to psychiatric care, including economic inequality, inadequate knowledge about mental health, and deficient social environments. These barriers have a significant impact on the accessibility of psychiatric health care within this community, and they need to be addressed.

Jegede et al2 discussed how financial woes and insecurity within the African American community contribute to health care inequalities and adverse health outcomes. According to the US Census Bureau,in 2020, compared to other ethnic groups, African American individuals had the lowest median income.3 Alang4 discussed how the stigma of mental health was a barrier among younger, college-educated individuals who are African American, and that those with higher education were more likely to minimize and report low treatment effectiveness. As clinicians, we often fail to discuss the effects the perceived social and cultural stigma of being diagnosed with a substance use or mental health disorder has on seeking care, treatment, and therapy by African American patients. The stigma of being judged by family members or the community and being seen as “weak” for seeking treatment has a detrimental impact on access to psychiatric care.2 It is our duty as clinicians to understand these kinds of stigmas and seek ways to mitigate them within this community.

Also, we must not underestimate the importance of patients having access to transportation to treatment. We know that social support is integral to treatment, recovery, and relapse prevention. Chronic cycles of treatment and relapse can occur due to inadequate social support. Having access to a reliable driver—especially one who is a family member or member of the community—can be vital to establishing social support. Jegede et al2 found that access to adequate transportation has proven therapeutic benefits and lessens the risk of relapse with decreased exposure to risky environments. We need to devise solutions to help patients find adequate and reliable transportation.

Clinicians should be culturally mindful and aware of the barriers to psychiatric care faced by patients who are African American. They should understand the importance of removing these barriers, and work to improve this population’s access to psychiatric care. Though this may be a daunting task that requires considerable time and resources, as health care providers, we can start the process by communicating and working with local politicians and community leaders. By working together, we can develop a plan to combat these socioeconomic barriers and provide access to psychiatric care within the African American community.

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD
 

Jersey Shore University Medical Center

Neptune, New Jersey

 

References
  1. Healthy People 2030, US Department of Health and Human Services, Office of Disease Prevention and Health Promotion. Social determinants of health. Accessed November 9, 2021. https://health.gov/healthypeople/objectives-and-data/social-determinants-health

    2. Jegede O, Muvvala S, Katehis E, et al. Perceived barriers to access care, anticipated discrimination and structural vulnerability among African Americans with substance use disorders. Int J Soc Psychiatry. 2021;67(2):136-143.

    3. Shrider EA, Kollar M, Chen F, et al. US Census Bureau, Current Population Reports, P60-273, Income and Poverty in the United States: 2020. US Government Publishing Office; 2021.
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Charles G. Kels, JD

Defense Health Agency San Antonio, Texas 

Mark S. Komrad, MD

Faculty of Psychiatry Johns Hopkins Hospital University of Maryland Tulane University Towson, Maryland

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD

Jersey Shore University Medical Center Neptune, New Jersey
 

Disclosures

The authors report no financial relationships with any companies whose products are mentioned in their letters, or with manufacturers of competing products.

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Defense Health Agency San Antonio, Texas 

Mark S. Komrad, MD

Faculty of Psychiatry Johns Hopkins Hospital University of Maryland Tulane University Towson, Maryland

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD

Jersey Shore University Medical Center Neptune, New Jersey
 

Disclosures

The authors report no financial relationships with any companies whose products are mentioned in their letters, or with manufacturers of competing products.

Author and Disclosure Information

Charles G. Kels, JD

Defense Health Agency San Antonio, Texas 

Mark S. Komrad, MD

Faculty of Psychiatry Johns Hopkins Hospital University of Maryland Tulane University Towson, Maryland

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD

Jersey Shore University Medical Center Neptune, New Jersey
 

Disclosures

The authors report no financial relationships with any companies whose products are mentioned in their letters, or with manufacturers of competing products.

Article PDF
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The perils of hubris

Dr. Nasrallah’s fascinating editorial on the psychiatric aspects of prominent individuals’ fall from grace (“From famous to infamous: Psychiatric aspects of the fall from grace,” From the Editor, Current Psychiatry, October 2021, p. 9-10,53) reminded me that the most trenchant insights and antidotes to hubris can more often be found in literature than in a diagnostic code. In Bonfire of the Vanities,1 Tom’s Wolfe’s satire on 1980s New York, self-proclaimed “Master of the Universe” Sherman McCoy lives in a Park Avenue high rise and works as a bond trader “on Wall Street, fifty floors up … overlooking the world!” As quickly becomes apparent, Sherman’s altitude—both literal and figurative—merely serves as a greater distance from which to fall.

Perhaps fittingly, the phenomenon of self-destruction as a byproduct of success was most prominently “diagnosed” by business school professors, not physicians. The propensity for ethical failure at the apex of achievement was coined the “Bathsheba Syndrome,” in reference to the biblical tale of King David’s degenerative sequence of temptation, infidelity, deceit, and treachery while at the height of his power.2 David’s transgressions are enabled by the very success he has achieved.3

One of my valued mentors had an interesting, albeit unscientific, method of mitigating hubris. When he was a senior military lawyer, or judge advocate (JAG), and I was a junior one, my mentor took me to a briefing in which he provided a legal overview to newly minted colonels assuming command billets. One of the functions of JAGs is to provide counsel and advice to commanders. As Dr. Nasrallah noted in his editorial, military leaders are by no means immune from the proverbial fall from grace, and arguably particularly susceptible to it. In beginning his remarks, my mentor offered his heartfelt congratulations to the attendees on their promotion and then proceeded to hand out a pocket mirror for them to pass around. He asked each officer to look in the mirror and personally confirm for him that they were just as unattractive today as they were yesterday.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas



The views expressed in this letter are those of the author and do not necessarily reflect those of any government agency.

1. Wolfe T. Bonfire of the vanities. Farrar, Straus and Giroux; 1987.

2. Ludwig DC, Longenecker CO. The Bathsheba syndrome: the ethical failure of successful leaders. J Bus Ethics. 1993;12:265-273.

3. 2 Samuel 11-12.

 

I enjoyed Dr. Nasrallah’s editorial and his discussion of the dangers of hubris. This brought to mind the role of the auriga in ancient Rome: "the auriga was a slave with gladiator status, whose duty it was to drive a biga, the light vehicle powered by two horses, to transport some important Romans, mainly duces (military commanders). An auriga was a sort of “chauffeur” for important men and was carefully selected from among trustworthy slaves only. It has been supposed also that this name was given to the slave who held a laurel crown, during Roman Triumphs, over the head of the dux, standing at his back but continuously whispering in his ears “Memento Mori” (“remember you are mortal”) to prevent the celebrated commander from losing his sense of proportion in the excesses of the celebrations.”1  

Continue to: Mark S. Komrad, MD...

 

 

Mark S. Komrad, MD

Faculty of Psychiatry

Johns Hopkins Hospital

University of Maryland

Tulane University

Towson, Maryland

Reference

1. Auriga (slave). Accessed November 9, 2021. https://en.wikipedia.org/wiki/Auriga_(slave)

Barriers to care faced by African American patients

According to the US Department of Health and Human Services, the 5 domains of social determinants of health are Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighbor­hood and Built Environment, and Social and Community Context.1 Patients who are African American face many socioeconomic barriers to access to psychiatric care, including economic inequality, inadequate knowledge about mental health, and deficient social environments. These barriers have a significant impact on the accessibility of psychiatric health care within this community, and they need to be addressed.

Jegede et al2 discussed how financial woes and insecurity within the African American community contribute to health care inequalities and adverse health outcomes. According to the US Census Bureau,in 2020, compared to other ethnic groups, African American individuals had the lowest median income.3 Alang4 discussed how the stigma of mental health was a barrier among younger, college-educated individuals who are African American, and that those with higher education were more likely to minimize and report low treatment effectiveness. As clinicians, we often fail to discuss the effects the perceived social and cultural stigma of being diagnosed with a substance use or mental health disorder has on seeking care, treatment, and therapy by African American patients. The stigma of being judged by family members or the community and being seen as “weak” for seeking treatment has a detrimental impact on access to psychiatric care.2 It is our duty as clinicians to understand these kinds of stigmas and seek ways to mitigate them within this community.

Also, we must not underestimate the importance of patients having access to transportation to treatment. We know that social support is integral to treatment, recovery, and relapse prevention. Chronic cycles of treatment and relapse can occur due to inadequate social support. Having access to a reliable driver—especially one who is a family member or member of the community—can be vital to establishing social support. Jegede et al2 found that access to adequate transportation has proven therapeutic benefits and lessens the risk of relapse with decreased exposure to risky environments. We need to devise solutions to help patients find adequate and reliable transportation.

Clinicians should be culturally mindful and aware of the barriers to psychiatric care faced by patients who are African American. They should understand the importance of removing these barriers, and work to improve this population’s access to psychiatric care. Though this may be a daunting task that requires considerable time and resources, as health care providers, we can start the process by communicating and working with local politicians and community leaders. By working together, we can develop a plan to combat these socioeconomic barriers and provide access to psychiatric care within the African American community.

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD
 

Jersey Shore University Medical Center

Neptune, New Jersey

 

 

The perils of hubris

Dr. Nasrallah’s fascinating editorial on the psychiatric aspects of prominent individuals’ fall from grace (“From famous to infamous: Psychiatric aspects of the fall from grace,” From the Editor, Current Psychiatry, October 2021, p. 9-10,53) reminded me that the most trenchant insights and antidotes to hubris can more often be found in literature than in a diagnostic code. In Bonfire of the Vanities,1 Tom’s Wolfe’s satire on 1980s New York, self-proclaimed “Master of the Universe” Sherman McCoy lives in a Park Avenue high rise and works as a bond trader “on Wall Street, fifty floors up … overlooking the world!” As quickly becomes apparent, Sherman’s altitude—both literal and figurative—merely serves as a greater distance from which to fall.

Perhaps fittingly, the phenomenon of self-destruction as a byproduct of success was most prominently “diagnosed” by business school professors, not physicians. The propensity for ethical failure at the apex of achievement was coined the “Bathsheba Syndrome,” in reference to the biblical tale of King David’s degenerative sequence of temptation, infidelity, deceit, and treachery while at the height of his power.2 David’s transgressions are enabled by the very success he has achieved.3

One of my valued mentors had an interesting, albeit unscientific, method of mitigating hubris. When he was a senior military lawyer, or judge advocate (JAG), and I was a junior one, my mentor took me to a briefing in which he provided a legal overview to newly minted colonels assuming command billets. One of the functions of JAGs is to provide counsel and advice to commanders. As Dr. Nasrallah noted in his editorial, military leaders are by no means immune from the proverbial fall from grace, and arguably particularly susceptible to it. In beginning his remarks, my mentor offered his heartfelt congratulations to the attendees on their promotion and then proceeded to hand out a pocket mirror for them to pass around. He asked each officer to look in the mirror and personally confirm for him that they were just as unattractive today as they were yesterday.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas



The views expressed in this letter are those of the author and do not necessarily reflect those of any government agency.

1. Wolfe T. Bonfire of the vanities. Farrar, Straus and Giroux; 1987.

2. Ludwig DC, Longenecker CO. The Bathsheba syndrome: the ethical failure of successful leaders. J Bus Ethics. 1993;12:265-273.

3. 2 Samuel 11-12.

 

I enjoyed Dr. Nasrallah’s editorial and his discussion of the dangers of hubris. This brought to mind the role of the auriga in ancient Rome: "the auriga was a slave with gladiator status, whose duty it was to drive a biga, the light vehicle powered by two horses, to transport some important Romans, mainly duces (military commanders). An auriga was a sort of “chauffeur” for important men and was carefully selected from among trustworthy slaves only. It has been supposed also that this name was given to the slave who held a laurel crown, during Roman Triumphs, over the head of the dux, standing at his back but continuously whispering in his ears “Memento Mori” (“remember you are mortal”) to prevent the celebrated commander from losing his sense of proportion in the excesses of the celebrations.”1  

Continue to: Mark S. Komrad, MD...

 

 

Mark S. Komrad, MD

Faculty of Psychiatry

Johns Hopkins Hospital

University of Maryland

Tulane University

Towson, Maryland

Reference

1. Auriga (slave). Accessed November 9, 2021. https://en.wikipedia.org/wiki/Auriga_(slave)

Barriers to care faced by African American patients

According to the US Department of Health and Human Services, the 5 domains of social determinants of health are Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighbor­hood and Built Environment, and Social and Community Context.1 Patients who are African American face many socioeconomic barriers to access to psychiatric care, including economic inequality, inadequate knowledge about mental health, and deficient social environments. These barriers have a significant impact on the accessibility of psychiatric health care within this community, and they need to be addressed.

Jegede et al2 discussed how financial woes and insecurity within the African American community contribute to health care inequalities and adverse health outcomes. According to the US Census Bureau,in 2020, compared to other ethnic groups, African American individuals had the lowest median income.3 Alang4 discussed how the stigma of mental health was a barrier among younger, college-educated individuals who are African American, and that those with higher education were more likely to minimize and report low treatment effectiveness. As clinicians, we often fail to discuss the effects the perceived social and cultural stigma of being diagnosed with a substance use or mental health disorder has on seeking care, treatment, and therapy by African American patients. The stigma of being judged by family members or the community and being seen as “weak” for seeking treatment has a detrimental impact on access to psychiatric care.2 It is our duty as clinicians to understand these kinds of stigmas and seek ways to mitigate them within this community.

Also, we must not underestimate the importance of patients having access to transportation to treatment. We know that social support is integral to treatment, recovery, and relapse prevention. Chronic cycles of treatment and relapse can occur due to inadequate social support. Having access to a reliable driver—especially one who is a family member or member of the community—can be vital to establishing social support. Jegede et al2 found that access to adequate transportation has proven therapeutic benefits and lessens the risk of relapse with decreased exposure to risky environments. We need to devise solutions to help patients find adequate and reliable transportation.

Clinicians should be culturally mindful and aware of the barriers to psychiatric care faced by patients who are African American. They should understand the importance of removing these barriers, and work to improve this population’s access to psychiatric care. Though this may be a daunting task that requires considerable time and resources, as health care providers, we can start the process by communicating and working with local politicians and community leaders. By working together, we can develop a plan to combat these socioeconomic barriers and provide access to psychiatric care within the African American community.

Craig Perry, MD

Elohor Otite, MD

Stacy Doumas, MD
 

Jersey Shore University Medical Center

Neptune, New Jersey

 

References
  1. Healthy People 2030, US Department of Health and Human Services, Office of Disease Prevention and Health Promotion. Social determinants of health. Accessed November 9, 2021. https://health.gov/healthypeople/objectives-and-data/social-determinants-health

    2. Jegede O, Muvvala S, Katehis E, et al. Perceived barriers to access care, anticipated discrimination and structural vulnerability among African Americans with substance use disorders. Int J Soc Psychiatry. 2021;67(2):136-143.

    3. Shrider EA, Kollar M, Chen F, et al. US Census Bureau, Current Population Reports, P60-273, Income and Poverty in the United States: 2020. US Government Publishing Office; 2021.
References
  1. Healthy People 2030, US Department of Health and Human Services, Office of Disease Prevention and Health Promotion. Social determinants of health. Accessed November 9, 2021. https://health.gov/healthypeople/objectives-and-data/social-determinants-health

    2. Jegede O, Muvvala S, Katehis E, et al. Perceived barriers to access care, anticipated discrimination and structural vulnerability among African Americans with substance use disorders. Int J Soc Psychiatry. 2021;67(2):136-143.

    3. Shrider EA, Kollar M, Chen F, et al. US Census Bureau, Current Population Reports, P60-273, Income and Poverty in the United States: 2020. US Government Publishing Office; 2021.
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Could stem cells have a role in treating mental illnesses?

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Thu, 12/02/2021 - 15:42

While laboratory studies move forward at full speed, the clinical use of stem cells—undifferentiated cells that can develop into many different types of specialized cells—remains controversial. Presently, only unadulterated stem cells are allowed to be used in patients, and only on an experimental and investigational basis. Stem cells that have been expanded, modified, or enhanced outside of the body are not allowed to be used for clinical application in the United States at this time. In June 2021, the FDA strengthened the language of stem cell regulation, further limiting their clinical application (see https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/important-patient-and-consumer-information-about-regenerative-medicine-therapies). Yet some applications, such as treatment of lymphoma or restorative knee injections, are covered by some health insurance plans, and the acceptance of stem cell treatment is growing.

In this article, I describe the basics of stem cells, and explore the potential therapeutic use of stem cells for treating various mental illnesses.

Stem cells: A primer

Human embryonic stem cells were initially investigated for their healing properties. However, the need to harvest these cells from embryos drew much criticism, and many found the process to be ethically and religiously unacceptable. This was resolved by the Nobel prize–winning discovery that adult somatic cells can be reprogrammed into cells with embryonic stem cell properties by introducing specific transcription factors. These cells have been termed “induced pluripotent stem cells” (iPSCs).1 The use of adult stem cells and stem cells from the umbilical cords of healthy newborns has allowed for wider acceptance of stem cell research and treatment.

Stem cells may be collected from the patient himself or herself; these are autologous stem cells. They may also be harvested from healthy newborn waste, such as the umbilical cord blood and wall; these are allogenic stem cells. Autologous stem cells are present in almost any tissue but are usually collected from the patient’s adipose tissue or from bone marrow. Understandably, younger stem cells possess higher healing properties. Stem cells may be mesenchymal, producing primarily connective and nervous tissue, or hematopoietic, influencing the immune system and blood cell production, though there is a considerable overlap in the function of these types of cells.

Adult somatic stem cells may be turned into stem cells (iPSCs) and then become any tissue, including neurons. This ability of stem cells to physically regenerate the CNS is directly relevant to psychiatry.

In addition to neurogenesis, stem cell transplants can assist in immune and vascular restoration as well as in suppressing inflammation. The ability of stem cells to replace mutated genes may be useful for addressing inheritable neuropsychiatric conditions.

Both autoimmune and inflammatory mechanisms play an important role in most psychiatric illnesses. The more we learn, the more it is clear that brain function is profoundly dependent on more than just its structure, and that structure depends on more than blood supply. Stem cells influence the vascular, nutritional, functional, inflammatory, and immune environment of the brain, potentially assisting in cognitive and emotional rehabilitation.

Stem cells operate in 2 fundamental ways: via direct cell-to-cell interaction, and via the production and release of growth, immune-regulating, and anti-inflammatory factors. Such factors are produced within the cells and then released in the extracellular environment as a content of exosomes. The route of administration is important in the delivery of the stem cells to the target tissue. Unlike their direct introduction into a joint, muscle, or intervertebral disk, injection of stem cells into the brain is more complicated and not routinely feasible. Intrathecal injections may bring stem cells into the CNS, but cerebrospinal fluid does not easily carry stem cells into the brain, and certainly cannot deliver them to an identified target within the brain. Existing technology can allow stem cells to be packaged in such a way that they can penetrate the blood-brain barrier, but this requires stem cell modification, which presently is not permitted in clinical practice in the United States. Alternatively, there is a way to weaken the blood-brain barrier to allow stem cells to travel through the “opened doors,” so to speak, but this allows everything to have access to the CNS, which may be unsafe. IV administration is technologically easy, and it grants stem cells the environment to multiply and produce extracellular factors that can cross the blood-brain barrier, while large cells cannot.

Continue to: Stem cells as a treatment for mental illness...

 

 

Stem cells as a treatment for mental illness

Based on our understanding of the function of stem cells, many neurodegenerative-, vascular-, immune-, and inflammation-based psychiatric conditions can be influenced by stem cell treatment. Here I review the potential therapeutic role of stem cells in the treatment of several psychiatric disorders.

Alzheimer’s dementia

Alzheimer’s dementia (AD) is a progressive neurodegenerative pathology based on neuronal and synaptic loss. Repopulation and regeneration of depleted neuronal circuitry by exogenous stem cells may be a rational therapeutic strategy.2 The regeneration of lost neurons has the potential to restore cognitive function. Multiple growth factors that regulate neurogenesis are abundant during child development but dramatically decline with age. The introduction of stem cells—especially those derived from newborn waste—seem to promote recovery from neuro­degenerative disease or injury.3

There currently is no cure for AD. Cellular therapy promises new advances in treatment.4 Neurogenesis occurs not only during fetal development but in the adult brain. Neural stem cells reside in the adult CNS of all mammals.5 They are intimately involved in continuous restoration, but age just like the rest of the animal tissue, providing ever-decreasing restorative potential.

The number of studies of stem cells in AD has increased since the early 2000 s,6,7 and research continues to demonstrate robust CNS neurogenesis. In a 2020 study, Zappa Villar et al8 evaluated stem cells as a treatment for rats in which an AD model was induced by the intracerebroventricular injection of streptozotocin (STZ). The STZ-treated rats displayed poor performance in all behavioral tests. Stem cell therapy increased exploratory behavior, decreased anxiety, and improved spatial memory and marble-burying behavior; the latter was representative of daily life activities. Importantly, stem cell therapy ameliorated and restored hippocampal atrophy and some presynaptic protein levels in the rats with AD.8 Animal models cannot be automatically applied to humans, but they shine a light on the areas that need further exploration.

In humans, elevated cortisol levels during aging predict hippocampal atrophy and memory deficits,9 and this deficiency may be positively influenced by stem cell treatment.

Schizophrenia

Recent research indicates that schizophrenia may begin with abnormal neurogenesis from neural stem cells inside the embryo, and that this process may be particularly vulnerable to numerous genetic and/or environmental disturbances of early brain development.10 Because neurogenesis is not confined to the womb but is a protracted process that continues into postnatal life, adolescence and beyond, influencing this process may be a way to add to the schizophrenia treatment armamentarium.10 Sacco et al11 described links between the alteration of intrauterine and adult neurogenesis and the causes of neuropsychiatric disorders, including schizophrenia. Immune and inflammatory mechanisms are important in the etiology of schizophrenia. By their core function, stem cells address both mechanisms, and may directly modulate this devastating disease.

In addition to clinical hopes, advances in research tools hold the promise of new discoveries. With the advent of iPSC technology, it is possible to generate live neurons in vitro from somatic tissue of patients with schizophrenia. Despite its many limitations, this revolutionary technology has already helped to advance our understanding of schizophrenia.11

Bipolar disorder

Many of the fundamental neurobiological mechanisms of schizophrenia are mirrored in bipolar disorder.12 Though we are not ready to bring stem cells into the day-to-day treatment of this condition, several groups are starting to apply iPSC technology to the study of bipolar disorder.13

Neurodevelopmental factors—particularly pathways related to nervous system development, cell migration, extracellular matrix, methylation, and calcium signaling—have been identified in large gene expression studies as altered in bipolar disorder.14 Stem cell technology opens doorways to reverse engineering of human neuro­degenerative disease.15


Continue to: Autism spectrum disorders...

 

 

Autism spectrum disorders

Autism spectrum disorders (ASDs) are multiple heterogeneous neurodevelopmental disorders.16 Neuroinflammation and immune dysregulation influence the origin of ASDs. Due to the neurobiologic changes underlying ASD development, cell-based therapies, including the use of mesenchymal stem cells (MSCs), have been applied to ASDs.16 Stem cells show specific immunologic properties that make them promising candidates for treating ASDs.17

The exact mechanisms of action of MSCs to restore function in patients with ASDs are largely unknown, but proposed mechanisms include:

  • synthesizing and releasing anti-inflammatory cytokines and survival-promoting growth factors
  • integrating into the existing neural and synaptic network
  • restoring plasticity.18

In a study of transplantation of human cord blood cells and umbilical cord–derived MSCs for patients with ASDs, Bradstreet et al19 found a statistically significant difference on scores for domains of speech, sociability, sensory, and overall health, as well as reductions in the total scores, in those who received transplants compared to their pretreatment values.

In another study of stem cell therapy for ASDs, Lv et al20 demonstrated the safety and efficacy of combined transplantation of human cord blood cells and umbilical cord–derived MSCs in treating children with ASDs. The transplantations included 4 stem cell IV infusions and intrathecal injections once a week. Statistically significant differences were shown at 24 weeks post-treatment. Although this nonrandomized, open-label, single-center Phase I/II trial cannot be relied on for any definitive conclusions, it suggests an important area of investigation.20

The vascular aspects of ASDs’ pathogenesis should not be overlooked. For example, specific temporal lobe areas associated with facial recognition, social interaction, and language comprehension have been demonstrated to be hypoperfused in children with ASDs, but not in controls. The degree of hypoperfusion and resulting hypoxia correlates with the severity of ASD symptoms. The damage causing hypoperfusion of temporal areas was associated with the onset of autism-like disorders. Damage of the amygdala, hippocampus, or other temporal structures induces permanent or transient autistic-like characteristics, such as unexpressive faces, little eye contact, and motor stereotypes. Clinically, temporal lobe damage by viral and other means has been implicated in the development of ASD in children and adults. Hypoperfusion may contribute to defects, not only by inducing hypoxia, but also by allowing for abnormal metabolite or neurotransmitter accumulation. This is one of the reasons glutamate toxicity has been implicated in ASD. The augmentation of perfusion through stimulation of angiogenesis by stem cells should allow for metabolite clearance and restoration of functionality. Vargas et al21 compared brain autopsy samples from 11 children with ASDs to those of 7 age-matched controls. They demonstrated an active neuroinflammatory process in the cerebral cortex, white matter, and cerebellum of patients with ASDs, both by immunohistochemistry and morphology.21

Multiple studies have confirmed that the systemic administration of cord blood cells is sufficient to induce neuroregeneration.22,23 Angiogenesis has been experimentally demonstrated in peripheral artery disease, myocardial ischemia, and stroke, and has direct implications on brain repair.24 Immune dysregulation25,26 and immune modulation27 also are addressed by stem cell treatment, which provides a promising avenue for battling ASDs.

Like attention-deficit/hyperactivity disorder and obsessive-compulsive disorder, ASDs are neurodevelopmental conditions. Advances based on the use of stem cells hold great promise for understanding, diagnosing and, possibly, treating these psychiatric disorders.28,29

Depression

Neuropsychiatric disorders arise from deviations from the regular differentiation process of the CNS, leading to altered neuronal connectivity. Relatively subtle abnormalities in the size and number of cells in the prefrontal cortex and basal ganglia have been observed in patients with depressive disorder and Tourette syndrome.30 Fibroblast-derived iPSCs generate serotonergic neurons through the exposure of the cells to growth factors and modulators of signaling pathways. If these serotonergic neurons are made from the patients’ own cells, they can be used to screen for new therapeutics and elucidate the unknown mechanisms through which current medications may function.31 This development could lead to the discovery of new medication targets and new insights into the molecular biology of depression.32

Deficiencies of brain-derived neurotrophic factor (BDNF) have a role in depression, anxiety, and other neuropsychiatric illnesses. The acute behavioral effects of selective serotonin reuptake inhibitors and tricyclic antidepressants seem to require BDNF signaling, which suggests that BDNF holds great potential as a therapeutic agent. Cell therapies focused on correcting BDNF deficiencies in mice have had some success.33

Dysregulation of GABAergic neurons has also been implicated in depression and anxiety. Patients with major depressive disorder have reduced gamma aminobutyric acid (GABA) receptors in the parahippocampal and lateral temporal lobes.34

Ultimately, the development of differentiation protocols for serotonergic and GABAergic neuronal populations will pave the way for examining the role of these populations in the pathogenesis of depression and anxiety, and may eventually open the door for cell-based therapies in humans.35

Studies have demonstrated a reduction in the density of pyramidal and nonpyramidal neurons in the anterior cingulate cortex of patients with schizophrenia and bipolar disorder,36 glial reduction in the subgenual prefrontal cortex in mood disorders,37 and morphometric evidence for neuronal and glial prefrontal cell pathology in major depressive disorder.38 The potential for stem cells to repair such pathology may be of clinical benefit to many patients.

Aside from their other suggested clinical uses, iPSCs may be utilized in new pathways for research on the biology and pharmacology of major depressive disorder.39

Continue to: Obsessive-compulsive disorder...

 

 

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is often characterized by excessive behaviors related to cleanliness, including grooming, which is represented across most animal species. In mice, behaviors such as compulsive grooming and hair removal—similar to behaviors in humans with OCD or trichotillomania—are associated with a specific mutation. Chen et al40 reported that the transplantation of bone marrow stem cells into mice with this mutation (bone marrow–derived microglia specifically home to the brain) rescues their pathological phenotype by repairing native neurons.

The autoimmune, inflammatory, and neurodegenerative changes that are prevalent in OCD may be remedied by stem cell treatment in a fashion described throughout this article.

Other conditions

The Box41-50 describes a possible role for stem cells in the treatment or prevention of several types of substance use disorders.

Box

Stem cells and substance use disorders

Researchers have begun to explore stem cells as a potential treatment for several substance use disorders, including those involving alcohol, cocaine, and opioids, as well as their interactions with cannabinoids.

Alcohol use disorder. In a 2017 study, Israel et al41 gave intra-cerebral injections of mesenchymal stem cells (MSCs) to rats that were bred to have a high alcohol intake. The MSC injections resulted in drastic reductions in the rats’ alcohol consumption. A single intracerebroventricular MSC administration inhibited relapse-like drinking by up to 85% for 40 days.

It is beyond unlikely that direct brain injections would be used to treat alcohol use disorder in humans. To address this problem, researchers aggregated MSCs into smaller spheroid shapes, which reduced their size up to 75% and allowed them to be injected intravenously to reach the brain in a study conducted in rats.42 Within 48 hours of a single treatment, the rats had reduced their intake of alcohol by 90%. The IV administration of antiinflammatory MSCs in human trials will be the next step to verify these results.

Alcohol research using human stem cells is also being conducted as a model system to understand the neural mechanisms of alcohol use disorder.43

Cocaine use disorder. In a grant proposal, Yadid and Popovtzer44 suggested that cocaine addiction affects neurogenesis, especially in the dentate gyrus, ventral tegmental area, nucleus accumbens, and prefrontal cortex; it damages mitochondrial RNA, brain-derived neurotrophic factor (BDNF), glutamate transporter (excitatory amino acid transporter; EAAT), and interleukin-10. MSCs have a predilection to these areas and influence neurogenesis. Currently, there are no FDAapproved medications for the safe and effective treatment of cocaine addiction. MSCs can home to pathological areas in the brain, release growth factors, and serve as cellular delivery tools in various brain disorders. Moreover, restoration of basal glutamate levels via the EAAT has been proposed as a promising target for treating cocaine dependence. Therefore, MSCs differentiated to express EAATs may have a combined long-term effect that can attenuate cocaine craving and relapse.44

Neural stem cells undergo a series of developmental processes before giving rise to newborn neurons, astrocytes, and oligodendrocytes in adult neurogenesis. During the past decade, studies of adult neurogenesis modulated by addictive drugs have highlighted the role of stem cells. These drugs have been shown to regulate the proliferation, differentiation, and survival of adult cells in different manners, which results in the varying consequences of adult neurogenesis.45 Reversal of these influences by healthy stem cells can be a worthy goal to pursue.

Opioid use disorder. Opiate medications cause a loss of newly born neural progenitors in the subgranular zone of the dentate gyrus by either modulating proliferation or interfering with differentiation and maturation.46 Opiates were the first medications shown to negatively impact neurogenesis in the adult mammalian hippocampus.47,48 The restoration of hippocampal function may positively affect the prognosis of a patient who is addicted.

Cannabinoids. Cannabinoids’ influence on the brain and on stem cells is controversial. On one hand, deteriorated neurogenesis results in reduced long-term potentiation in hippocampal formation. These cellular and physiological alterations lead to decreased short-term spatial memory and increased depressionlike behaviors.49 On the other hand, there is emerging evidence that cannabinoids improve neurogenesis and CNS plasticity, at least in the adult mouse.50 Through normalization of immune function, and restoration of the brain and the body, stem cells may assist in better health and in treatment of cannabis use disorder.

Chronic pain is a neuropsychiatric condition that involves the immune system, inflammation, vascularization, trophic changes, and other aspects of the CNS function in addition to peripheral factors and somatic pain generators. Treatment of painful conditions with the aid of stem cells represents a large and ever-developing field that lies outside of the scope of this article.51

 

Experimental, but promising

It is not easy to accept revolutionary new approaches in medicine. Endless research and due diligence are needed to prove a concept and then to work out specific applications, safeguards, and limitations for any novel treatments. The stem cell terrain is poorly explored, and one needs to be careful when venturing there. Presently, the FDA appropriately sees treatment with stem cells as experimental and investigational, particularly in the mental health arena. Stem cells are not approved for treatment of any specific condition. At the same time, research and clinical practice suggest stem cell treatment may someday play a more prominent role in health care. Undoubtedly, psychiatry will eventually benefit from the knowledge and application of stem cell research and practice.

Related Resources

  • De Los Angeles A, Fernando MB, Hall NAL, et al. Induced pluripotent stem cells in psychiatry: an overview and critical perspective. Biol Psychiatry. 2021;90(6):362-372.
  • Heider J, Vogel S, Volkmer H, et al. Human iPSC-derived glia as a tool for neuropsychiatric research and drug development. Int J Mol Sci. 2021;22(19):10254.

Drug Brand Name

Streptozotocin • Zanosar

Bottom Line

Treatment with stem cell transplantation is experimental and not approved for any medical or psychiatric illness. However, based on our growing understanding of the function of stem cells, and preliminary research conducted mainly in animals, many neurodegenerative-, vascular-, immune-, and inflammation-based psychiatric conditions might be beneficially influenced by stem cell treatment.

References
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  7. Li M, Guo K, Ikehara S. Stem cell treatment for Alzheimer’s disease. Int J Mol Sci. 2014;15(10):19226-19238.
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  12.  Miller ND, Kelsoe JR. Unraveling the biology of bipolar disorder using induced pluripotent stem-derived neurons. Bipolar Disord. 2017;19(7):544-551.
  13. O’Shea KS, McInnis MG. Neurodevelopmental origins of bipolar disorder: iPSC models. Mol Cell Neurosci. 2016;73:63-83.
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Indiana Polyclinic
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Indianapolis, Indiana

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The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

Author and Disclosure Information

Dmitry M. Arbuck, MD

President and Medical Director
Indiana Polyclinic
Indianapolis, Indiana

Disclosure

The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

Article PDF
Article PDF

While laboratory studies move forward at full speed, the clinical use of stem cells—undifferentiated cells that can develop into many different types of specialized cells—remains controversial. Presently, only unadulterated stem cells are allowed to be used in patients, and only on an experimental and investigational basis. Stem cells that have been expanded, modified, or enhanced outside of the body are not allowed to be used for clinical application in the United States at this time. In June 2021, the FDA strengthened the language of stem cell regulation, further limiting their clinical application (see https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/important-patient-and-consumer-information-about-regenerative-medicine-therapies). Yet some applications, such as treatment of lymphoma or restorative knee injections, are covered by some health insurance plans, and the acceptance of stem cell treatment is growing.

In this article, I describe the basics of stem cells, and explore the potential therapeutic use of stem cells for treating various mental illnesses.

Stem cells: A primer

Human embryonic stem cells were initially investigated for their healing properties. However, the need to harvest these cells from embryos drew much criticism, and many found the process to be ethically and religiously unacceptable. This was resolved by the Nobel prize–winning discovery that adult somatic cells can be reprogrammed into cells with embryonic stem cell properties by introducing specific transcription factors. These cells have been termed “induced pluripotent stem cells” (iPSCs).1 The use of adult stem cells and stem cells from the umbilical cords of healthy newborns has allowed for wider acceptance of stem cell research and treatment.

Stem cells may be collected from the patient himself or herself; these are autologous stem cells. They may also be harvested from healthy newborn waste, such as the umbilical cord blood and wall; these are allogenic stem cells. Autologous stem cells are present in almost any tissue but are usually collected from the patient’s adipose tissue or from bone marrow. Understandably, younger stem cells possess higher healing properties. Stem cells may be mesenchymal, producing primarily connective and nervous tissue, or hematopoietic, influencing the immune system and blood cell production, though there is a considerable overlap in the function of these types of cells.

Adult somatic stem cells may be turned into stem cells (iPSCs) and then become any tissue, including neurons. This ability of stem cells to physically regenerate the CNS is directly relevant to psychiatry.

In addition to neurogenesis, stem cell transplants can assist in immune and vascular restoration as well as in suppressing inflammation. The ability of stem cells to replace mutated genes may be useful for addressing inheritable neuropsychiatric conditions.

Both autoimmune and inflammatory mechanisms play an important role in most psychiatric illnesses. The more we learn, the more it is clear that brain function is profoundly dependent on more than just its structure, and that structure depends on more than blood supply. Stem cells influence the vascular, nutritional, functional, inflammatory, and immune environment of the brain, potentially assisting in cognitive and emotional rehabilitation.

Stem cells operate in 2 fundamental ways: via direct cell-to-cell interaction, and via the production and release of growth, immune-regulating, and anti-inflammatory factors. Such factors are produced within the cells and then released in the extracellular environment as a content of exosomes. The route of administration is important in the delivery of the stem cells to the target tissue. Unlike their direct introduction into a joint, muscle, or intervertebral disk, injection of stem cells into the brain is more complicated and not routinely feasible. Intrathecal injections may bring stem cells into the CNS, but cerebrospinal fluid does not easily carry stem cells into the brain, and certainly cannot deliver them to an identified target within the brain. Existing technology can allow stem cells to be packaged in such a way that they can penetrate the blood-brain barrier, but this requires stem cell modification, which presently is not permitted in clinical practice in the United States. Alternatively, there is a way to weaken the blood-brain barrier to allow stem cells to travel through the “opened doors,” so to speak, but this allows everything to have access to the CNS, which may be unsafe. IV administration is technologically easy, and it grants stem cells the environment to multiply and produce extracellular factors that can cross the blood-brain barrier, while large cells cannot.

Continue to: Stem cells as a treatment for mental illness...

 

 

Stem cells as a treatment for mental illness

Based on our understanding of the function of stem cells, many neurodegenerative-, vascular-, immune-, and inflammation-based psychiatric conditions can be influenced by stem cell treatment. Here I review the potential therapeutic role of stem cells in the treatment of several psychiatric disorders.

Alzheimer’s dementia

Alzheimer’s dementia (AD) is a progressive neurodegenerative pathology based on neuronal and synaptic loss. Repopulation and regeneration of depleted neuronal circuitry by exogenous stem cells may be a rational therapeutic strategy.2 The regeneration of lost neurons has the potential to restore cognitive function. Multiple growth factors that regulate neurogenesis are abundant during child development but dramatically decline with age. The introduction of stem cells—especially those derived from newborn waste—seem to promote recovery from neuro­degenerative disease or injury.3

There currently is no cure for AD. Cellular therapy promises new advances in treatment.4 Neurogenesis occurs not only during fetal development but in the adult brain. Neural stem cells reside in the adult CNS of all mammals.5 They are intimately involved in continuous restoration, but age just like the rest of the animal tissue, providing ever-decreasing restorative potential.

The number of studies of stem cells in AD has increased since the early 2000 s,6,7 and research continues to demonstrate robust CNS neurogenesis. In a 2020 study, Zappa Villar et al8 evaluated stem cells as a treatment for rats in which an AD model was induced by the intracerebroventricular injection of streptozotocin (STZ). The STZ-treated rats displayed poor performance in all behavioral tests. Stem cell therapy increased exploratory behavior, decreased anxiety, and improved spatial memory and marble-burying behavior; the latter was representative of daily life activities. Importantly, stem cell therapy ameliorated and restored hippocampal atrophy and some presynaptic protein levels in the rats with AD.8 Animal models cannot be automatically applied to humans, but they shine a light on the areas that need further exploration.

In humans, elevated cortisol levels during aging predict hippocampal atrophy and memory deficits,9 and this deficiency may be positively influenced by stem cell treatment.

Schizophrenia

Recent research indicates that schizophrenia may begin with abnormal neurogenesis from neural stem cells inside the embryo, and that this process may be particularly vulnerable to numerous genetic and/or environmental disturbances of early brain development.10 Because neurogenesis is not confined to the womb but is a protracted process that continues into postnatal life, adolescence and beyond, influencing this process may be a way to add to the schizophrenia treatment armamentarium.10 Sacco et al11 described links between the alteration of intrauterine and adult neurogenesis and the causes of neuropsychiatric disorders, including schizophrenia. Immune and inflammatory mechanisms are important in the etiology of schizophrenia. By their core function, stem cells address both mechanisms, and may directly modulate this devastating disease.

In addition to clinical hopes, advances in research tools hold the promise of new discoveries. With the advent of iPSC technology, it is possible to generate live neurons in vitro from somatic tissue of patients with schizophrenia. Despite its many limitations, this revolutionary technology has already helped to advance our understanding of schizophrenia.11

Bipolar disorder

Many of the fundamental neurobiological mechanisms of schizophrenia are mirrored in bipolar disorder.12 Though we are not ready to bring stem cells into the day-to-day treatment of this condition, several groups are starting to apply iPSC technology to the study of bipolar disorder.13

Neurodevelopmental factors—particularly pathways related to nervous system development, cell migration, extracellular matrix, methylation, and calcium signaling—have been identified in large gene expression studies as altered in bipolar disorder.14 Stem cell technology opens doorways to reverse engineering of human neuro­degenerative disease.15


Continue to: Autism spectrum disorders...

 

 

Autism spectrum disorders

Autism spectrum disorders (ASDs) are multiple heterogeneous neurodevelopmental disorders.16 Neuroinflammation and immune dysregulation influence the origin of ASDs. Due to the neurobiologic changes underlying ASD development, cell-based therapies, including the use of mesenchymal stem cells (MSCs), have been applied to ASDs.16 Stem cells show specific immunologic properties that make them promising candidates for treating ASDs.17

The exact mechanisms of action of MSCs to restore function in patients with ASDs are largely unknown, but proposed mechanisms include:

  • synthesizing and releasing anti-inflammatory cytokines and survival-promoting growth factors
  • integrating into the existing neural and synaptic network
  • restoring plasticity.18

In a study of transplantation of human cord blood cells and umbilical cord–derived MSCs for patients with ASDs, Bradstreet et al19 found a statistically significant difference on scores for domains of speech, sociability, sensory, and overall health, as well as reductions in the total scores, in those who received transplants compared to their pretreatment values.

In another study of stem cell therapy for ASDs, Lv et al20 demonstrated the safety and efficacy of combined transplantation of human cord blood cells and umbilical cord–derived MSCs in treating children with ASDs. The transplantations included 4 stem cell IV infusions and intrathecal injections once a week. Statistically significant differences were shown at 24 weeks post-treatment. Although this nonrandomized, open-label, single-center Phase I/II trial cannot be relied on for any definitive conclusions, it suggests an important area of investigation.20

The vascular aspects of ASDs’ pathogenesis should not be overlooked. For example, specific temporal lobe areas associated with facial recognition, social interaction, and language comprehension have been demonstrated to be hypoperfused in children with ASDs, but not in controls. The degree of hypoperfusion and resulting hypoxia correlates with the severity of ASD symptoms. The damage causing hypoperfusion of temporal areas was associated with the onset of autism-like disorders. Damage of the amygdala, hippocampus, or other temporal structures induces permanent or transient autistic-like characteristics, such as unexpressive faces, little eye contact, and motor stereotypes. Clinically, temporal lobe damage by viral and other means has been implicated in the development of ASD in children and adults. Hypoperfusion may contribute to defects, not only by inducing hypoxia, but also by allowing for abnormal metabolite or neurotransmitter accumulation. This is one of the reasons glutamate toxicity has been implicated in ASD. The augmentation of perfusion through stimulation of angiogenesis by stem cells should allow for metabolite clearance and restoration of functionality. Vargas et al21 compared brain autopsy samples from 11 children with ASDs to those of 7 age-matched controls. They demonstrated an active neuroinflammatory process in the cerebral cortex, white matter, and cerebellum of patients with ASDs, both by immunohistochemistry and morphology.21

Multiple studies have confirmed that the systemic administration of cord blood cells is sufficient to induce neuroregeneration.22,23 Angiogenesis has been experimentally demonstrated in peripheral artery disease, myocardial ischemia, and stroke, and has direct implications on brain repair.24 Immune dysregulation25,26 and immune modulation27 also are addressed by stem cell treatment, which provides a promising avenue for battling ASDs.

Like attention-deficit/hyperactivity disorder and obsessive-compulsive disorder, ASDs are neurodevelopmental conditions. Advances based on the use of stem cells hold great promise for understanding, diagnosing and, possibly, treating these psychiatric disorders.28,29

Depression

Neuropsychiatric disorders arise from deviations from the regular differentiation process of the CNS, leading to altered neuronal connectivity. Relatively subtle abnormalities in the size and number of cells in the prefrontal cortex and basal ganglia have been observed in patients with depressive disorder and Tourette syndrome.30 Fibroblast-derived iPSCs generate serotonergic neurons through the exposure of the cells to growth factors and modulators of signaling pathways. If these serotonergic neurons are made from the patients’ own cells, they can be used to screen for new therapeutics and elucidate the unknown mechanisms through which current medications may function.31 This development could lead to the discovery of new medication targets and new insights into the molecular biology of depression.32

Deficiencies of brain-derived neurotrophic factor (BDNF) have a role in depression, anxiety, and other neuropsychiatric illnesses. The acute behavioral effects of selective serotonin reuptake inhibitors and tricyclic antidepressants seem to require BDNF signaling, which suggests that BDNF holds great potential as a therapeutic agent. Cell therapies focused on correcting BDNF deficiencies in mice have had some success.33

Dysregulation of GABAergic neurons has also been implicated in depression and anxiety. Patients with major depressive disorder have reduced gamma aminobutyric acid (GABA) receptors in the parahippocampal and lateral temporal lobes.34

Ultimately, the development of differentiation protocols for serotonergic and GABAergic neuronal populations will pave the way for examining the role of these populations in the pathogenesis of depression and anxiety, and may eventually open the door for cell-based therapies in humans.35

Studies have demonstrated a reduction in the density of pyramidal and nonpyramidal neurons in the anterior cingulate cortex of patients with schizophrenia and bipolar disorder,36 glial reduction in the subgenual prefrontal cortex in mood disorders,37 and morphometric evidence for neuronal and glial prefrontal cell pathology in major depressive disorder.38 The potential for stem cells to repair such pathology may be of clinical benefit to many patients.

Aside from their other suggested clinical uses, iPSCs may be utilized in new pathways for research on the biology and pharmacology of major depressive disorder.39

Continue to: Obsessive-compulsive disorder...

 

 

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is often characterized by excessive behaviors related to cleanliness, including grooming, which is represented across most animal species. In mice, behaviors such as compulsive grooming and hair removal—similar to behaviors in humans with OCD or trichotillomania—are associated with a specific mutation. Chen et al40 reported that the transplantation of bone marrow stem cells into mice with this mutation (bone marrow–derived microglia specifically home to the brain) rescues their pathological phenotype by repairing native neurons.

The autoimmune, inflammatory, and neurodegenerative changes that are prevalent in OCD may be remedied by stem cell treatment in a fashion described throughout this article.

Other conditions

The Box41-50 describes a possible role for stem cells in the treatment or prevention of several types of substance use disorders.

Box

Stem cells and substance use disorders

Researchers have begun to explore stem cells as a potential treatment for several substance use disorders, including those involving alcohol, cocaine, and opioids, as well as their interactions with cannabinoids.

Alcohol use disorder. In a 2017 study, Israel et al41 gave intra-cerebral injections of mesenchymal stem cells (MSCs) to rats that were bred to have a high alcohol intake. The MSC injections resulted in drastic reductions in the rats’ alcohol consumption. A single intracerebroventricular MSC administration inhibited relapse-like drinking by up to 85% for 40 days.

It is beyond unlikely that direct brain injections would be used to treat alcohol use disorder in humans. To address this problem, researchers aggregated MSCs into smaller spheroid shapes, which reduced their size up to 75% and allowed them to be injected intravenously to reach the brain in a study conducted in rats.42 Within 48 hours of a single treatment, the rats had reduced their intake of alcohol by 90%. The IV administration of antiinflammatory MSCs in human trials will be the next step to verify these results.

Alcohol research using human stem cells is also being conducted as a model system to understand the neural mechanisms of alcohol use disorder.43

Cocaine use disorder. In a grant proposal, Yadid and Popovtzer44 suggested that cocaine addiction affects neurogenesis, especially in the dentate gyrus, ventral tegmental area, nucleus accumbens, and prefrontal cortex; it damages mitochondrial RNA, brain-derived neurotrophic factor (BDNF), glutamate transporter (excitatory amino acid transporter; EAAT), and interleukin-10. MSCs have a predilection to these areas and influence neurogenesis. Currently, there are no FDAapproved medications for the safe and effective treatment of cocaine addiction. MSCs can home to pathological areas in the brain, release growth factors, and serve as cellular delivery tools in various brain disorders. Moreover, restoration of basal glutamate levels via the EAAT has been proposed as a promising target for treating cocaine dependence. Therefore, MSCs differentiated to express EAATs may have a combined long-term effect that can attenuate cocaine craving and relapse.44

Neural stem cells undergo a series of developmental processes before giving rise to newborn neurons, astrocytes, and oligodendrocytes in adult neurogenesis. During the past decade, studies of adult neurogenesis modulated by addictive drugs have highlighted the role of stem cells. These drugs have been shown to regulate the proliferation, differentiation, and survival of adult cells in different manners, which results in the varying consequences of adult neurogenesis.45 Reversal of these influences by healthy stem cells can be a worthy goal to pursue.

Opioid use disorder. Opiate medications cause a loss of newly born neural progenitors in the subgranular zone of the dentate gyrus by either modulating proliferation or interfering with differentiation and maturation.46 Opiates were the first medications shown to negatively impact neurogenesis in the adult mammalian hippocampus.47,48 The restoration of hippocampal function may positively affect the prognosis of a patient who is addicted.

Cannabinoids. Cannabinoids’ influence on the brain and on stem cells is controversial. On one hand, deteriorated neurogenesis results in reduced long-term potentiation in hippocampal formation. These cellular and physiological alterations lead to decreased short-term spatial memory and increased depressionlike behaviors.49 On the other hand, there is emerging evidence that cannabinoids improve neurogenesis and CNS plasticity, at least in the adult mouse.50 Through normalization of immune function, and restoration of the brain and the body, stem cells may assist in better health and in treatment of cannabis use disorder.

Chronic pain is a neuropsychiatric condition that involves the immune system, inflammation, vascularization, trophic changes, and other aspects of the CNS function in addition to peripheral factors and somatic pain generators. Treatment of painful conditions with the aid of stem cells represents a large and ever-developing field that lies outside of the scope of this article.51

 

Experimental, but promising

It is not easy to accept revolutionary new approaches in medicine. Endless research and due diligence are needed to prove a concept and then to work out specific applications, safeguards, and limitations for any novel treatments. The stem cell terrain is poorly explored, and one needs to be careful when venturing there. Presently, the FDA appropriately sees treatment with stem cells as experimental and investigational, particularly in the mental health arena. Stem cells are not approved for treatment of any specific condition. At the same time, research and clinical practice suggest stem cell treatment may someday play a more prominent role in health care. Undoubtedly, psychiatry will eventually benefit from the knowledge and application of stem cell research and practice.

Related Resources

  • De Los Angeles A, Fernando MB, Hall NAL, et al. Induced pluripotent stem cells in psychiatry: an overview and critical perspective. Biol Psychiatry. 2021;90(6):362-372.
  • Heider J, Vogel S, Volkmer H, et al. Human iPSC-derived glia as a tool for neuropsychiatric research and drug development. Int J Mol Sci. 2021;22(19):10254.

Drug Brand Name

Streptozotocin • Zanosar

Bottom Line

Treatment with stem cell transplantation is experimental and not approved for any medical or psychiatric illness. However, based on our growing understanding of the function of stem cells, and preliminary research conducted mainly in animals, many neurodegenerative-, vascular-, immune-, and inflammation-based psychiatric conditions might be beneficially influenced by stem cell treatment.

While laboratory studies move forward at full speed, the clinical use of stem cells—undifferentiated cells that can develop into many different types of specialized cells—remains controversial. Presently, only unadulterated stem cells are allowed to be used in patients, and only on an experimental and investigational basis. Stem cells that have been expanded, modified, or enhanced outside of the body are not allowed to be used for clinical application in the United States at this time. In June 2021, the FDA strengthened the language of stem cell regulation, further limiting their clinical application (see https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/important-patient-and-consumer-information-about-regenerative-medicine-therapies). Yet some applications, such as treatment of lymphoma or restorative knee injections, are covered by some health insurance plans, and the acceptance of stem cell treatment is growing.

In this article, I describe the basics of stem cells, and explore the potential therapeutic use of stem cells for treating various mental illnesses.

Stem cells: A primer

Human embryonic stem cells were initially investigated for their healing properties. However, the need to harvest these cells from embryos drew much criticism, and many found the process to be ethically and religiously unacceptable. This was resolved by the Nobel prize–winning discovery that adult somatic cells can be reprogrammed into cells with embryonic stem cell properties by introducing specific transcription factors. These cells have been termed “induced pluripotent stem cells” (iPSCs).1 The use of adult stem cells and stem cells from the umbilical cords of healthy newborns has allowed for wider acceptance of stem cell research and treatment.

Stem cells may be collected from the patient himself or herself; these are autologous stem cells. They may also be harvested from healthy newborn waste, such as the umbilical cord blood and wall; these are allogenic stem cells. Autologous stem cells are present in almost any tissue but are usually collected from the patient’s adipose tissue or from bone marrow. Understandably, younger stem cells possess higher healing properties. Stem cells may be mesenchymal, producing primarily connective and nervous tissue, or hematopoietic, influencing the immune system and blood cell production, though there is a considerable overlap in the function of these types of cells.

Adult somatic stem cells may be turned into stem cells (iPSCs) and then become any tissue, including neurons. This ability of stem cells to physically regenerate the CNS is directly relevant to psychiatry.

In addition to neurogenesis, stem cell transplants can assist in immune and vascular restoration as well as in suppressing inflammation. The ability of stem cells to replace mutated genes may be useful for addressing inheritable neuropsychiatric conditions.

Both autoimmune and inflammatory mechanisms play an important role in most psychiatric illnesses. The more we learn, the more it is clear that brain function is profoundly dependent on more than just its structure, and that structure depends on more than blood supply. Stem cells influence the vascular, nutritional, functional, inflammatory, and immune environment of the brain, potentially assisting in cognitive and emotional rehabilitation.

Stem cells operate in 2 fundamental ways: via direct cell-to-cell interaction, and via the production and release of growth, immune-regulating, and anti-inflammatory factors. Such factors are produced within the cells and then released in the extracellular environment as a content of exosomes. The route of administration is important in the delivery of the stem cells to the target tissue. Unlike their direct introduction into a joint, muscle, or intervertebral disk, injection of stem cells into the brain is more complicated and not routinely feasible. Intrathecal injections may bring stem cells into the CNS, but cerebrospinal fluid does not easily carry stem cells into the brain, and certainly cannot deliver them to an identified target within the brain. Existing technology can allow stem cells to be packaged in such a way that they can penetrate the blood-brain barrier, but this requires stem cell modification, which presently is not permitted in clinical practice in the United States. Alternatively, there is a way to weaken the blood-brain barrier to allow stem cells to travel through the “opened doors,” so to speak, but this allows everything to have access to the CNS, which may be unsafe. IV administration is technologically easy, and it grants stem cells the environment to multiply and produce extracellular factors that can cross the blood-brain barrier, while large cells cannot.

Continue to: Stem cells as a treatment for mental illness...

 

 

Stem cells as a treatment for mental illness

Based on our understanding of the function of stem cells, many neurodegenerative-, vascular-, immune-, and inflammation-based psychiatric conditions can be influenced by stem cell treatment. Here I review the potential therapeutic role of stem cells in the treatment of several psychiatric disorders.

Alzheimer’s dementia

Alzheimer’s dementia (AD) is a progressive neurodegenerative pathology based on neuronal and synaptic loss. Repopulation and regeneration of depleted neuronal circuitry by exogenous stem cells may be a rational therapeutic strategy.2 The regeneration of lost neurons has the potential to restore cognitive function. Multiple growth factors that regulate neurogenesis are abundant during child development but dramatically decline with age. The introduction of stem cells—especially those derived from newborn waste—seem to promote recovery from neuro­degenerative disease or injury.3

There currently is no cure for AD. Cellular therapy promises new advances in treatment.4 Neurogenesis occurs not only during fetal development but in the adult brain. Neural stem cells reside in the adult CNS of all mammals.5 They are intimately involved in continuous restoration, but age just like the rest of the animal tissue, providing ever-decreasing restorative potential.

The number of studies of stem cells in AD has increased since the early 2000 s,6,7 and research continues to demonstrate robust CNS neurogenesis. In a 2020 study, Zappa Villar et al8 evaluated stem cells as a treatment for rats in which an AD model was induced by the intracerebroventricular injection of streptozotocin (STZ). The STZ-treated rats displayed poor performance in all behavioral tests. Stem cell therapy increased exploratory behavior, decreased anxiety, and improved spatial memory and marble-burying behavior; the latter was representative of daily life activities. Importantly, stem cell therapy ameliorated and restored hippocampal atrophy and some presynaptic protein levels in the rats with AD.8 Animal models cannot be automatically applied to humans, but they shine a light on the areas that need further exploration.

In humans, elevated cortisol levels during aging predict hippocampal atrophy and memory deficits,9 and this deficiency may be positively influenced by stem cell treatment.

Schizophrenia

Recent research indicates that schizophrenia may begin with abnormal neurogenesis from neural stem cells inside the embryo, and that this process may be particularly vulnerable to numerous genetic and/or environmental disturbances of early brain development.10 Because neurogenesis is not confined to the womb but is a protracted process that continues into postnatal life, adolescence and beyond, influencing this process may be a way to add to the schizophrenia treatment armamentarium.10 Sacco et al11 described links between the alteration of intrauterine and adult neurogenesis and the causes of neuropsychiatric disorders, including schizophrenia. Immune and inflammatory mechanisms are important in the etiology of schizophrenia. By their core function, stem cells address both mechanisms, and may directly modulate this devastating disease.

In addition to clinical hopes, advances in research tools hold the promise of new discoveries. With the advent of iPSC technology, it is possible to generate live neurons in vitro from somatic tissue of patients with schizophrenia. Despite its many limitations, this revolutionary technology has already helped to advance our understanding of schizophrenia.11

Bipolar disorder

Many of the fundamental neurobiological mechanisms of schizophrenia are mirrored in bipolar disorder.12 Though we are not ready to bring stem cells into the day-to-day treatment of this condition, several groups are starting to apply iPSC technology to the study of bipolar disorder.13

Neurodevelopmental factors—particularly pathways related to nervous system development, cell migration, extracellular matrix, methylation, and calcium signaling—have been identified in large gene expression studies as altered in bipolar disorder.14 Stem cell technology opens doorways to reverse engineering of human neuro­degenerative disease.15


Continue to: Autism spectrum disorders...

 

 

Autism spectrum disorders

Autism spectrum disorders (ASDs) are multiple heterogeneous neurodevelopmental disorders.16 Neuroinflammation and immune dysregulation influence the origin of ASDs. Due to the neurobiologic changes underlying ASD development, cell-based therapies, including the use of mesenchymal stem cells (MSCs), have been applied to ASDs.16 Stem cells show specific immunologic properties that make them promising candidates for treating ASDs.17

The exact mechanisms of action of MSCs to restore function in patients with ASDs are largely unknown, but proposed mechanisms include:

  • synthesizing and releasing anti-inflammatory cytokines and survival-promoting growth factors
  • integrating into the existing neural and synaptic network
  • restoring plasticity.18

In a study of transplantation of human cord blood cells and umbilical cord–derived MSCs for patients with ASDs, Bradstreet et al19 found a statistically significant difference on scores for domains of speech, sociability, sensory, and overall health, as well as reductions in the total scores, in those who received transplants compared to their pretreatment values.

In another study of stem cell therapy for ASDs, Lv et al20 demonstrated the safety and efficacy of combined transplantation of human cord blood cells and umbilical cord–derived MSCs in treating children with ASDs. The transplantations included 4 stem cell IV infusions and intrathecal injections once a week. Statistically significant differences were shown at 24 weeks post-treatment. Although this nonrandomized, open-label, single-center Phase I/II trial cannot be relied on for any definitive conclusions, it suggests an important area of investigation.20

The vascular aspects of ASDs’ pathogenesis should not be overlooked. For example, specific temporal lobe areas associated with facial recognition, social interaction, and language comprehension have been demonstrated to be hypoperfused in children with ASDs, but not in controls. The degree of hypoperfusion and resulting hypoxia correlates with the severity of ASD symptoms. The damage causing hypoperfusion of temporal areas was associated with the onset of autism-like disorders. Damage of the amygdala, hippocampus, or other temporal structures induces permanent or transient autistic-like characteristics, such as unexpressive faces, little eye contact, and motor stereotypes. Clinically, temporal lobe damage by viral and other means has been implicated in the development of ASD in children and adults. Hypoperfusion may contribute to defects, not only by inducing hypoxia, but also by allowing for abnormal metabolite or neurotransmitter accumulation. This is one of the reasons glutamate toxicity has been implicated in ASD. The augmentation of perfusion through stimulation of angiogenesis by stem cells should allow for metabolite clearance and restoration of functionality. Vargas et al21 compared brain autopsy samples from 11 children with ASDs to those of 7 age-matched controls. They demonstrated an active neuroinflammatory process in the cerebral cortex, white matter, and cerebellum of patients with ASDs, both by immunohistochemistry and morphology.21

Multiple studies have confirmed that the systemic administration of cord blood cells is sufficient to induce neuroregeneration.22,23 Angiogenesis has been experimentally demonstrated in peripheral artery disease, myocardial ischemia, and stroke, and has direct implications on brain repair.24 Immune dysregulation25,26 and immune modulation27 also are addressed by stem cell treatment, which provides a promising avenue for battling ASDs.

Like attention-deficit/hyperactivity disorder and obsessive-compulsive disorder, ASDs are neurodevelopmental conditions. Advances based on the use of stem cells hold great promise for understanding, diagnosing and, possibly, treating these psychiatric disorders.28,29

Depression

Neuropsychiatric disorders arise from deviations from the regular differentiation process of the CNS, leading to altered neuronal connectivity. Relatively subtle abnormalities in the size and number of cells in the prefrontal cortex and basal ganglia have been observed in patients with depressive disorder and Tourette syndrome.30 Fibroblast-derived iPSCs generate serotonergic neurons through the exposure of the cells to growth factors and modulators of signaling pathways. If these serotonergic neurons are made from the patients’ own cells, they can be used to screen for new therapeutics and elucidate the unknown mechanisms through which current medications may function.31 This development could lead to the discovery of new medication targets and new insights into the molecular biology of depression.32

Deficiencies of brain-derived neurotrophic factor (BDNF) have a role in depression, anxiety, and other neuropsychiatric illnesses. The acute behavioral effects of selective serotonin reuptake inhibitors and tricyclic antidepressants seem to require BDNF signaling, which suggests that BDNF holds great potential as a therapeutic agent. Cell therapies focused on correcting BDNF deficiencies in mice have had some success.33

Dysregulation of GABAergic neurons has also been implicated in depression and anxiety. Patients with major depressive disorder have reduced gamma aminobutyric acid (GABA) receptors in the parahippocampal and lateral temporal lobes.34

Ultimately, the development of differentiation protocols for serotonergic and GABAergic neuronal populations will pave the way for examining the role of these populations in the pathogenesis of depression and anxiety, and may eventually open the door for cell-based therapies in humans.35

Studies have demonstrated a reduction in the density of pyramidal and nonpyramidal neurons in the anterior cingulate cortex of patients with schizophrenia and bipolar disorder,36 glial reduction in the subgenual prefrontal cortex in mood disorders,37 and morphometric evidence for neuronal and glial prefrontal cell pathology in major depressive disorder.38 The potential for stem cells to repair such pathology may be of clinical benefit to many patients.

Aside from their other suggested clinical uses, iPSCs may be utilized in new pathways for research on the biology and pharmacology of major depressive disorder.39

Continue to: Obsessive-compulsive disorder...

 

 

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is often characterized by excessive behaviors related to cleanliness, including grooming, which is represented across most animal species. In mice, behaviors such as compulsive grooming and hair removal—similar to behaviors in humans with OCD or trichotillomania—are associated with a specific mutation. Chen et al40 reported that the transplantation of bone marrow stem cells into mice with this mutation (bone marrow–derived microglia specifically home to the brain) rescues their pathological phenotype by repairing native neurons.

The autoimmune, inflammatory, and neurodegenerative changes that are prevalent in OCD may be remedied by stem cell treatment in a fashion described throughout this article.

Other conditions

The Box41-50 describes a possible role for stem cells in the treatment or prevention of several types of substance use disorders.

Box

Stem cells and substance use disorders

Researchers have begun to explore stem cells as a potential treatment for several substance use disorders, including those involving alcohol, cocaine, and opioids, as well as their interactions with cannabinoids.

Alcohol use disorder. In a 2017 study, Israel et al41 gave intra-cerebral injections of mesenchymal stem cells (MSCs) to rats that were bred to have a high alcohol intake. The MSC injections resulted in drastic reductions in the rats’ alcohol consumption. A single intracerebroventricular MSC administration inhibited relapse-like drinking by up to 85% for 40 days.

It is beyond unlikely that direct brain injections would be used to treat alcohol use disorder in humans. To address this problem, researchers aggregated MSCs into smaller spheroid shapes, which reduced their size up to 75% and allowed them to be injected intravenously to reach the brain in a study conducted in rats.42 Within 48 hours of a single treatment, the rats had reduced their intake of alcohol by 90%. The IV administration of antiinflammatory MSCs in human trials will be the next step to verify these results.

Alcohol research using human stem cells is also being conducted as a model system to understand the neural mechanisms of alcohol use disorder.43

Cocaine use disorder. In a grant proposal, Yadid and Popovtzer44 suggested that cocaine addiction affects neurogenesis, especially in the dentate gyrus, ventral tegmental area, nucleus accumbens, and prefrontal cortex; it damages mitochondrial RNA, brain-derived neurotrophic factor (BDNF), glutamate transporter (excitatory amino acid transporter; EAAT), and interleukin-10. MSCs have a predilection to these areas and influence neurogenesis. Currently, there are no FDAapproved medications for the safe and effective treatment of cocaine addiction. MSCs can home to pathological areas in the brain, release growth factors, and serve as cellular delivery tools in various brain disorders. Moreover, restoration of basal glutamate levels via the EAAT has been proposed as a promising target for treating cocaine dependence. Therefore, MSCs differentiated to express EAATs may have a combined long-term effect that can attenuate cocaine craving and relapse.44

Neural stem cells undergo a series of developmental processes before giving rise to newborn neurons, astrocytes, and oligodendrocytes in adult neurogenesis. During the past decade, studies of adult neurogenesis modulated by addictive drugs have highlighted the role of stem cells. These drugs have been shown to regulate the proliferation, differentiation, and survival of adult cells in different manners, which results in the varying consequences of adult neurogenesis.45 Reversal of these influences by healthy stem cells can be a worthy goal to pursue.

Opioid use disorder. Opiate medications cause a loss of newly born neural progenitors in the subgranular zone of the dentate gyrus by either modulating proliferation or interfering with differentiation and maturation.46 Opiates were the first medications shown to negatively impact neurogenesis in the adult mammalian hippocampus.47,48 The restoration of hippocampal function may positively affect the prognosis of a patient who is addicted.

Cannabinoids. Cannabinoids’ influence on the brain and on stem cells is controversial. On one hand, deteriorated neurogenesis results in reduced long-term potentiation in hippocampal formation. These cellular and physiological alterations lead to decreased short-term spatial memory and increased depressionlike behaviors.49 On the other hand, there is emerging evidence that cannabinoids improve neurogenesis and CNS plasticity, at least in the adult mouse.50 Through normalization of immune function, and restoration of the brain and the body, stem cells may assist in better health and in treatment of cannabis use disorder.

Chronic pain is a neuropsychiatric condition that involves the immune system, inflammation, vascularization, trophic changes, and other aspects of the CNS function in addition to peripheral factors and somatic pain generators. Treatment of painful conditions with the aid of stem cells represents a large and ever-developing field that lies outside of the scope of this article.51

 

Experimental, but promising

It is not easy to accept revolutionary new approaches in medicine. Endless research and due diligence are needed to prove a concept and then to work out specific applications, safeguards, and limitations for any novel treatments. The stem cell terrain is poorly explored, and one needs to be careful when venturing there. Presently, the FDA appropriately sees treatment with stem cells as experimental and investigational, particularly in the mental health arena. Stem cells are not approved for treatment of any specific condition. At the same time, research and clinical practice suggest stem cell treatment may someday play a more prominent role in health care. Undoubtedly, psychiatry will eventually benefit from the knowledge and application of stem cell research and practice.

Related Resources

  • De Los Angeles A, Fernando MB, Hall NAL, et al. Induced pluripotent stem cells in psychiatry: an overview and critical perspective. Biol Psychiatry. 2021;90(6):362-372.
  • Heider J, Vogel S, Volkmer H, et al. Human iPSC-derived glia as a tool for neuropsychiatric research and drug development. Int J Mol Sci. 2021;22(19):10254.

Drug Brand Name

Streptozotocin • Zanosar

Bottom Line

Treatment with stem cell transplantation is experimental and not approved for any medical or psychiatric illness. However, based on our growing understanding of the function of stem cells, and preliminary research conducted mainly in animals, many neurodegenerative-, vascular-, immune-, and inflammation-based psychiatric conditions might be beneficially influenced by stem cell treatment.

References
  1. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861-872.
  2. Duncan T, Valenzuela M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res Ther. 2017;8(1):111.
  3. Brinton RD, Wang JM. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer’s disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 2006;3(3):185-190.
  4. Taupin P. Adult neurogenesis, neural stem cells, and Alzheimer’s disease: developments, limitations, problems, and promises. Curr Alzheimer Res. 2009;6(6):461-470.
  5. Taupin P. Neurogenesis, NSCs, pathogenesis, and therapies for Alzheimer’s disease. Front Biosci (Schol Ed). 2011;3:178-90.
  6. Kang JM, Yeon BK, Cho SJ, et al. Stem cell therapy for Alzheimer’s disease: a review of recent clinical trials. J Alzheimers Dis. 2016;54(3):879-889.
  7. Li M, Guo K, Ikehara S. Stem cell treatment for Alzheimer’s disease. Int J Mol Sci. 2014;15(10):19226-19238.
  8. Zappa Villar MF, López Hanotte J, Pardo J, et al. Mesenchymal stem cells therapy improved the streptozotocin-induced behavioral and hippocampal impairment in rats. Mol Neurobiol. 2020;57(2):600-615.
  9. Lupien SJ, de Leon M, de Santi S, et al. Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci. 1998;1(1):69-73.
  10. Iannitelli A, Quartini A, Tirassa P, et al. Schizophrenia and neurogenesis: a stem cell approach. Neurosci Biobehav Rev. 2017;80:414-442.
  11. Sacco R, Cacci E, Novarino G. Neural stem cells in neuropsychiatric disorders. Curr Opin Neurobiol. 2018; 48:131-138.
  12.  Miller ND, Kelsoe JR. Unraveling the biology of bipolar disorder using induced pluripotent stem-derived neurons. Bipolar Disord. 2017;19(7):544-551.
  13. O’Shea KS, McInnis MG. Neurodevelopmental origins of bipolar disorder: iPSC models. Mol Cell Neurosci. 2016;73:63-83.
  14. Jacobs BM. A dangerous method? The use of induced pluripotent stem cells as a model for schizophrenia. Schizophr Res. 2015;168(1-2):563-568.
  15. Liu Y, Deng W. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology. Brain Res. 2016;1638(Pt A):30-41.
  16. Siniscalco D, Kannan S, Semprún-Hernández N, et al. Stem cell therapy in autism: recent insights. Stem Cells Cloning. 2018;11:55-67.
  17. Siniscalco D, Bradstreet JJ, Sych N, et al. Mesenchymal stem cells in treating autism: novel insights. World J Stem Cells. 2014;6(2):173-178.
  18. Siniscalco D, Sapone A, Cirillo A, et al. Autism spectrum disorders: is mesenchymal stem cell personalized therapy the future? J Biomed Biotechnol. 2012; 2012:480289.
  19.  Bradstreet JJ, Sych N, Antonucci N, et al. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. Cell Transplant. 2014;23(Suppl 1):S105-S112.
  20. Lv YT, Zhang Y, Liu M, et al. Transplantation of human cord blood mononuclear cells and umbilical cordderived mesenchymal stem cells in autism. J Transl Med. 2013;11:196.
  21. Vargas DL, Nascimbene C, Krishnan C, et al. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67-81.
  22. Wei L, Keogh CL, Whitaker VR, et al. Angiogenesis and stem cell transplantation as potential treatments of cerebral ischemic stroke. Pathophysiology. 2005;12(1): 47-62.
  23. Newman MB, Willing AE, Manresa JJ, et al. Cytokines produced by cultured human umbilical cord blood (HUCB) cells: implications for brain repair. Exp Neurol. 2006;199(1):201-218.
  24. Peterson DA. Umbilical cord blood cells and brain stroke injury: bringing in fresh blood to address an old problem. J Clin Invest. 2004;114(3):312-314.
  25. Cohly HH, Panja A. Immunological findings in autism. Int Rev Neurobiol. 2005;71:317-341.
  26. Ashwood P, Van de Water J. Is autism an autoimmune disease? Autoimmun Rev. 2004;3(7-8):557-562.
  27. Yagi H, Soto-Gutierrez A, Parekkadan B, et al. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant. 2010;19(6):667-679.
  28. Vaccarino FM, Urban AE, Stevens HE, et al. Annual Research Review: The promise of stem cell research for neuropsychiatric disorders. J Child Psychol Psychiatry. 2011;52(4):504-516.
  29.  Liu EY, Scott CT. Great expectations: autism spectrum disorder and induced pluripotent stem cell technologies. Stem Cell Rev Rep. 2014;10(2):145-150.
  30. Richardson-Jones JW, Craige CP, Guiard BP, et al. 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron. 2010;65(1):40-52.
  31. Saarelainen T, Hendolin P, Lucas G, et al. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci. 2003;23(1):349-357.
  32. Klumpers UM, Veltman DJ, Drent ML, et al. Reduced parahippocampal and lateral temporal GABAA-[11C] flumazenil binding in major depression: preliminary results. Eur J Nucl Med Mol Imaging. 2010;37(3): 565-574.
  33. Bremner JD, Narayan M, Anderson ER, et al. Hippocampal volume reduction in major depression. Am J Psychiatry. 2000;157(1):115-118.
  34. Bremner JD, Randall P, Scott TM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995;152(7):973-981.
  35.  Vincent SL, Todtenkopf MS, Benes FM. A comparison of the density of pyramidal and non-pyramidal neurons in the anterior cingulate cortex of schizophrenics and manic depressives. Soc Neurosci Abstr. 1997;23:2199.
  36. Benes FM, Kwok EW, Vincent SL, et al. A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry. 1998;44(2): 88-97.
  37. Ongür D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A. 1998;95(22):13290-13295.
  38. Rajkowska G, Miguel-Hidalgo JJ, Wei J, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999;45(9): 1085-1098.
  39. Licinio J, Wong ML. Serotonergic neurons derived from induced pluripotent stem cells (iPSCs): a new pathway for research on the biology and pharmacology of major depression. Mol Psychiatry. 2016;21(1):1-2.
  40. Chen SK, Tvrdik P, Peden E, et al. Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell. 2010;141(5):775-785.
  41. Israel Y, Ezquer F, Quintanilla ME, et al. Intracerebral stem cell administration inhibits relapse-like alcohol drinking in rats. Alcohol Alcohol. 2017;52(1):1-4.
  42. Ezquer F, Morales P, Quintanilla ME, et al. Intravenous administration of anti-inflammatory mesenchymal stem cell spheroids reduces chronic alcohol intake and abolishes binge-drinking. Sci Rep. 2018;8(1):4325.
  43. Scarnati MS, Halikere A, Pang ZP. Using human stem cells as a model system to understand the neural mechanisms of alcohol use disorders: current status and outlook. Alcohol. 2019;74:83-93.
  44. Yadid GM, Popovtzer R. Nanoparticle-mesenchymal stem cell conjugates for cell therapy in drug addiction. NIH grant application. 2017.
  45. Xu C, Loh HH, Law PY. Effects of addictive drugs on adult neural stem/progenitor cells. Cell Mol Life Sci. 2016;73(2):327-348.
  46. Dholakiya SL, Aliberti A, Barile FA. Morphine sulfate concomitantly decreases neuronal differentiation and opioid receptor expression in mouse embryonic stem cells. Toxicol Lett. 2016;247:45-55.
  47. Zhang Y, Loh HH, Law PY. Effect of opioid on adult hippocampal neurogenesis. Scientific World Journal. 2016;2016:2601264.
  48. Bortolotto V, Grilli M. Opiate analgesics as negative modulators of adult hippocampal neurogenesis: potential implications in clinical practice. Front Pharmacol. 2017; 8:254.
  49. Galve-Roperh I, Chiurchiù V, Díaz-Alonso J, et al. Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation. Prog Lipid Res. 2013; 52(4):633-650.
  50. Zimmermann T, Maroso M, Beer A, et al. Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus. Cereb Cortex. 2018;28(12):4454-4471.
  51. Ren J, Liu N, Sun N, et al. Mesenchymal stem cells and their exosomes: promising therapies for chronic pain. Curr Stem Cell Res Ther. 2019;14(8):644-653.
References
  1. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861-872.
  2. Duncan T, Valenzuela M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res Ther. 2017;8(1):111.
  3. Brinton RD, Wang JM. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer’s disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 2006;3(3):185-190.
  4. Taupin P. Adult neurogenesis, neural stem cells, and Alzheimer’s disease: developments, limitations, problems, and promises. Curr Alzheimer Res. 2009;6(6):461-470.
  5. Taupin P. Neurogenesis, NSCs, pathogenesis, and therapies for Alzheimer’s disease. Front Biosci (Schol Ed). 2011;3:178-90.
  6. Kang JM, Yeon BK, Cho SJ, et al. Stem cell therapy for Alzheimer’s disease: a review of recent clinical trials. J Alzheimers Dis. 2016;54(3):879-889.
  7. Li M, Guo K, Ikehara S. Stem cell treatment for Alzheimer’s disease. Int J Mol Sci. 2014;15(10):19226-19238.
  8. Zappa Villar MF, López Hanotte J, Pardo J, et al. Mesenchymal stem cells therapy improved the streptozotocin-induced behavioral and hippocampal impairment in rats. Mol Neurobiol. 2020;57(2):600-615.
  9. Lupien SJ, de Leon M, de Santi S, et al. Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci. 1998;1(1):69-73.
  10. Iannitelli A, Quartini A, Tirassa P, et al. Schizophrenia and neurogenesis: a stem cell approach. Neurosci Biobehav Rev. 2017;80:414-442.
  11. Sacco R, Cacci E, Novarino G. Neural stem cells in neuropsychiatric disorders. Curr Opin Neurobiol. 2018; 48:131-138.
  12.  Miller ND, Kelsoe JR. Unraveling the biology of bipolar disorder using induced pluripotent stem-derived neurons. Bipolar Disord. 2017;19(7):544-551.
  13. O’Shea KS, McInnis MG. Neurodevelopmental origins of bipolar disorder: iPSC models. Mol Cell Neurosci. 2016;73:63-83.
  14. Jacobs BM. A dangerous method? The use of induced pluripotent stem cells as a model for schizophrenia. Schizophr Res. 2015;168(1-2):563-568.
  15. Liu Y, Deng W. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology. Brain Res. 2016;1638(Pt A):30-41.
  16. Siniscalco D, Kannan S, Semprún-Hernández N, et al. Stem cell therapy in autism: recent insights. Stem Cells Cloning. 2018;11:55-67.
  17. Siniscalco D, Bradstreet JJ, Sych N, et al. Mesenchymal stem cells in treating autism: novel insights. World J Stem Cells. 2014;6(2):173-178.
  18. Siniscalco D, Sapone A, Cirillo A, et al. Autism spectrum disorders: is mesenchymal stem cell personalized therapy the future? J Biomed Biotechnol. 2012; 2012:480289.
  19.  Bradstreet JJ, Sych N, Antonucci N, et al. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. Cell Transplant. 2014;23(Suppl 1):S105-S112.
  20. Lv YT, Zhang Y, Liu M, et al. Transplantation of human cord blood mononuclear cells and umbilical cordderived mesenchymal stem cells in autism. J Transl Med. 2013;11:196.
  21. Vargas DL, Nascimbene C, Krishnan C, et al. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67-81.
  22. Wei L, Keogh CL, Whitaker VR, et al. Angiogenesis and stem cell transplantation as potential treatments of cerebral ischemic stroke. Pathophysiology. 2005;12(1): 47-62.
  23. Newman MB, Willing AE, Manresa JJ, et al. Cytokines produced by cultured human umbilical cord blood (HUCB) cells: implications for brain repair. Exp Neurol. 2006;199(1):201-218.
  24. Peterson DA. Umbilical cord blood cells and brain stroke injury: bringing in fresh blood to address an old problem. J Clin Invest. 2004;114(3):312-314.
  25. Cohly HH, Panja A. Immunological findings in autism. Int Rev Neurobiol. 2005;71:317-341.
  26. Ashwood P, Van de Water J. Is autism an autoimmune disease? Autoimmun Rev. 2004;3(7-8):557-562.
  27. Yagi H, Soto-Gutierrez A, Parekkadan B, et al. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant. 2010;19(6):667-679.
  28. Vaccarino FM, Urban AE, Stevens HE, et al. Annual Research Review: The promise of stem cell research for neuropsychiatric disorders. J Child Psychol Psychiatry. 2011;52(4):504-516.
  29.  Liu EY, Scott CT. Great expectations: autism spectrum disorder and induced pluripotent stem cell technologies. Stem Cell Rev Rep. 2014;10(2):145-150.
  30. Richardson-Jones JW, Craige CP, Guiard BP, et al. 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron. 2010;65(1):40-52.
  31. Saarelainen T, Hendolin P, Lucas G, et al. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci. 2003;23(1):349-357.
  32. Klumpers UM, Veltman DJ, Drent ML, et al. Reduced parahippocampal and lateral temporal GABAA-[11C] flumazenil binding in major depression: preliminary results. Eur J Nucl Med Mol Imaging. 2010;37(3): 565-574.
  33. Bremner JD, Narayan M, Anderson ER, et al. Hippocampal volume reduction in major depression. Am J Psychiatry. 2000;157(1):115-118.
  34. Bremner JD, Randall P, Scott TM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995;152(7):973-981.
  35.  Vincent SL, Todtenkopf MS, Benes FM. A comparison of the density of pyramidal and non-pyramidal neurons in the anterior cingulate cortex of schizophrenics and manic depressives. Soc Neurosci Abstr. 1997;23:2199.
  36. Benes FM, Kwok EW, Vincent SL, et al. A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry. 1998;44(2): 88-97.
  37. Ongür D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A. 1998;95(22):13290-13295.
  38. Rajkowska G, Miguel-Hidalgo JJ, Wei J, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999;45(9): 1085-1098.
  39. Licinio J, Wong ML. Serotonergic neurons derived from induced pluripotent stem cells (iPSCs): a new pathway for research on the biology and pharmacology of major depression. Mol Psychiatry. 2016;21(1):1-2.
  40. Chen SK, Tvrdik P, Peden E, et al. Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell. 2010;141(5):775-785.
  41. Israel Y, Ezquer F, Quintanilla ME, et al. Intracerebral stem cell administration inhibits relapse-like alcohol drinking in rats. Alcohol Alcohol. 2017;52(1):1-4.
  42. Ezquer F, Morales P, Quintanilla ME, et al. Intravenous administration of anti-inflammatory mesenchymal stem cell spheroids reduces chronic alcohol intake and abolishes binge-drinking. Sci Rep. 2018;8(1):4325.
  43. Scarnati MS, Halikere A, Pang ZP. Using human stem cells as a model system to understand the neural mechanisms of alcohol use disorders: current status and outlook. Alcohol. 2019;74:83-93.
  44. Yadid GM, Popovtzer R. Nanoparticle-mesenchymal stem cell conjugates for cell therapy in drug addiction. NIH grant application. 2017.
  45. Xu C, Loh HH, Law PY. Effects of addictive drugs on adult neural stem/progenitor cells. Cell Mol Life Sci. 2016;73(2):327-348.
  46. Dholakiya SL, Aliberti A, Barile FA. Morphine sulfate concomitantly decreases neuronal differentiation and opioid receptor expression in mouse embryonic stem cells. Toxicol Lett. 2016;247:45-55.
  47. Zhang Y, Loh HH, Law PY. Effect of opioid on adult hippocampal neurogenesis. Scientific World Journal. 2016;2016:2601264.
  48. Bortolotto V, Grilli M. Opiate analgesics as negative modulators of adult hippocampal neurogenesis: potential implications in clinical practice. Front Pharmacol. 2017; 8:254.
  49. Galve-Roperh I, Chiurchiù V, Díaz-Alonso J, et al. Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation. Prog Lipid Res. 2013; 52(4):633-650.
  50. Zimmermann T, Maroso M, Beer A, et al. Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus. Cereb Cortex. 2018;28(12):4454-4471.
  51. Ren J, Liu N, Sun N, et al. Mesenchymal stem cells and their exosomes: promising therapies for chronic pain. Curr Stem Cell Res Ther. 2019;14(8):644-653.
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We physicians must pull together as a knowledge community

Article Type
Changed
Tue, 11/30/2021 - 10:13

The COVID-19 pandemic is a biosocial phenomenon. Patients and doctors alike find themselves assigned to groups designated as responsible and wise, or selfish and irrational, based strictly upon their personal assessments of medical risk. This trend in our culture is represented by threats of disciplinary action issued by medical regulators against physicians who are perceived to be undermining the public health message by spreading “misinformation.”

Dr. Renée S. Kohanski

Our review of the literature reveals many references to “misinformation” but no definition narrow and precise enough to be interpreted consistently in a disciplinary environment. More pressing, this ambiguous word’s use is correlated with negative meaning and innuendo, often discrediting valuable information a priori without actual data points.

Dr. Robert S. Emmons

The most basic definition available is Merriam Webster’s: “incorrect or misleading information.” This definition includes no point of reference against which competing scientific claims can be measured.

Claudia E. Haupt, PhD, a political scientist and law professor, articulates a useful framework for understanding the relationship between medicine and state regulators. In the Yale Law Journal, Dr. Haupt wrote: “Knowledge communities have specialized expertise and are closest to those affected; they must have the freedom to work things out for themselves. The professions as knowledge communities have a fundamental interest in not having the state (or anyone else, for that matter) corrupt or distort what amounts to the state of the art in their respective fields.”

Injecting the artificial term “misinformation” into the science information ecosystem obfuscates and impedes the very ability of this vital knowledge community to perform its raison d’être. Use of the term misinformation with no clear scientific parameters ultimately makes it into a word that discredits, restrains, and incites, rather than attending to healing or promoting progress.

Time has certainly shown us that science is anything but settled on all things COVID. If the scientific community accepts disrespect as the response of choice to difference of opinion and practice, we lose the trust in one another as colleagues; we need to keep scientific inquiry and exploration alive. Curiosity, equanimity, and tolerance are key components of the professional attitude as we deftly maneuver against the virus together.

In the face of deadly disease, it is especially imperative that intelligent, thoughtful, highly respected scientists, researchers, and physicians have room to safely share their knowledge and clinical experience. The Association of American Physicians and Surgeons has published a statement on scientific integrity that can be used as a measuring stick for claims about misinformation in medicine. We call on physicians to pull together as a knowledge community. Kindness and respect for patients starts with kindness and respect for one another as colleagues.
 

Dr. Kohanski is in private practice in Somerset, N.J., and is a diplomate of the American Board of Psychiatry & Neurology. She disclosed no relevant financial relationships. Dr. Emmons is part-time clinical associate professor in the department of psychiatry at the University of Vermont, Burlington, and is a past chair of the Ethics Committee for the Vermont District Branch of the American Psychiatric Association. He is in private practice in Moretown, Vt., and disclosed no relevant financial relationships.

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The COVID-19 pandemic is a biosocial phenomenon. Patients and doctors alike find themselves assigned to groups designated as responsible and wise, or selfish and irrational, based strictly upon their personal assessments of medical risk. This trend in our culture is represented by threats of disciplinary action issued by medical regulators against physicians who are perceived to be undermining the public health message by spreading “misinformation.”

Dr. Renée S. Kohanski

Our review of the literature reveals many references to “misinformation” but no definition narrow and precise enough to be interpreted consistently in a disciplinary environment. More pressing, this ambiguous word’s use is correlated with negative meaning and innuendo, often discrediting valuable information a priori without actual data points.

Dr. Robert S. Emmons

The most basic definition available is Merriam Webster’s: “incorrect or misleading information.” This definition includes no point of reference against which competing scientific claims can be measured.

Claudia E. Haupt, PhD, a political scientist and law professor, articulates a useful framework for understanding the relationship between medicine and state regulators. In the Yale Law Journal, Dr. Haupt wrote: “Knowledge communities have specialized expertise and are closest to those affected; they must have the freedom to work things out for themselves. The professions as knowledge communities have a fundamental interest in not having the state (or anyone else, for that matter) corrupt or distort what amounts to the state of the art in their respective fields.”

Injecting the artificial term “misinformation” into the science information ecosystem obfuscates and impedes the very ability of this vital knowledge community to perform its raison d’être. Use of the term misinformation with no clear scientific parameters ultimately makes it into a word that discredits, restrains, and incites, rather than attending to healing or promoting progress.

Time has certainly shown us that science is anything but settled on all things COVID. If the scientific community accepts disrespect as the response of choice to difference of opinion and practice, we lose the trust in one another as colleagues; we need to keep scientific inquiry and exploration alive. Curiosity, equanimity, and tolerance are key components of the professional attitude as we deftly maneuver against the virus together.

In the face of deadly disease, it is especially imperative that intelligent, thoughtful, highly respected scientists, researchers, and physicians have room to safely share their knowledge and clinical experience. The Association of American Physicians and Surgeons has published a statement on scientific integrity that can be used as a measuring stick for claims about misinformation in medicine. We call on physicians to pull together as a knowledge community. Kindness and respect for patients starts with kindness and respect for one another as colleagues.
 

Dr. Kohanski is in private practice in Somerset, N.J., and is a diplomate of the American Board of Psychiatry & Neurology. She disclosed no relevant financial relationships. Dr. Emmons is part-time clinical associate professor in the department of psychiatry at the University of Vermont, Burlington, and is a past chair of the Ethics Committee for the Vermont District Branch of the American Psychiatric Association. He is in private practice in Moretown, Vt., and disclosed no relevant financial relationships.

The COVID-19 pandemic is a biosocial phenomenon. Patients and doctors alike find themselves assigned to groups designated as responsible and wise, or selfish and irrational, based strictly upon their personal assessments of medical risk. This trend in our culture is represented by threats of disciplinary action issued by medical regulators against physicians who are perceived to be undermining the public health message by spreading “misinformation.”

Dr. Renée S. Kohanski

Our review of the literature reveals many references to “misinformation” but no definition narrow and precise enough to be interpreted consistently in a disciplinary environment. More pressing, this ambiguous word’s use is correlated with negative meaning and innuendo, often discrediting valuable information a priori without actual data points.

Dr. Robert S. Emmons

The most basic definition available is Merriam Webster’s: “incorrect or misleading information.” This definition includes no point of reference against which competing scientific claims can be measured.

Claudia E. Haupt, PhD, a political scientist and law professor, articulates a useful framework for understanding the relationship between medicine and state regulators. In the Yale Law Journal, Dr. Haupt wrote: “Knowledge communities have specialized expertise and are closest to those affected; they must have the freedom to work things out for themselves. The professions as knowledge communities have a fundamental interest in not having the state (or anyone else, for that matter) corrupt or distort what amounts to the state of the art in their respective fields.”

Injecting the artificial term “misinformation” into the science information ecosystem obfuscates and impedes the very ability of this vital knowledge community to perform its raison d’être. Use of the term misinformation with no clear scientific parameters ultimately makes it into a word that discredits, restrains, and incites, rather than attending to healing or promoting progress.

Time has certainly shown us that science is anything but settled on all things COVID. If the scientific community accepts disrespect as the response of choice to difference of opinion and practice, we lose the trust in one another as colleagues; we need to keep scientific inquiry and exploration alive. Curiosity, equanimity, and tolerance are key components of the professional attitude as we deftly maneuver against the virus together.

In the face of deadly disease, it is especially imperative that intelligent, thoughtful, highly respected scientists, researchers, and physicians have room to safely share their knowledge and clinical experience. The Association of American Physicians and Surgeons has published a statement on scientific integrity that can be used as a measuring stick for claims about misinformation in medicine. We call on physicians to pull together as a knowledge community. Kindness and respect for patients starts with kindness and respect for one another as colleagues.
 

Dr. Kohanski is in private practice in Somerset, N.J., and is a diplomate of the American Board of Psychiatry & Neurology. She disclosed no relevant financial relationships. Dr. Emmons is part-time clinical associate professor in the department of psychiatry at the University of Vermont, Burlington, and is a past chair of the Ethics Committee for the Vermont District Branch of the American Psychiatric Association. He is in private practice in Moretown, Vt., and disclosed no relevant financial relationships.

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Adolescents, THC, and the risk of psychosis

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Fri, 12/03/2021 - 11:44

 

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.
 

Since the recent legalization and decriminalization of cannabis (marijuana) use throughout the United States, adolescents’ access to, and use of, cannabis has increased.1 Cannabis products have been marketed in ways that attract adolescents, such as edible gummies, cookies, and hard candies, as well as by vaping.1 The adolescent years are a delicate period of development during which individuals are prone to psychiatric illness, including depression, anxiety, and psychosis.2,3 Here we discuss the relationship between adolescent cannabis use and the development of psychosis.

How cannabis can affect the adolescent brain

The 2 main psychotropic substances found within the cannabis plant are tetrahydrocannabinol (THC) and cannabidiol (CBD).1,4 Endocannabinoids are fatty acid derivatives produced in the brain that bind to cannabinoid (CB) receptors found in the brain and the peripheral nervous system.1,4

During adolescence, neurodevelopment and neurochemical balances are evolving, and it’s during this period that the bulk of prefrontal pruning occurs, especially in the glutamatergic and gamma aminobutyric acidergic (GABAergic) neural pathways.5 THC affects the CB1 receptors by downregulating the neuron receptors, which then alters the maturation of the prefrontal cortical GABAergic neurons. Also, THC affects the upregulation of the microglia located on the CB2 receptors, thereby altering synaptic pruning even further.2,5

All of these changes can cause brain insults that can contribute to the precipitation of psychotic decompensation in adolescents who ingest products that contain THC. In addition, consuming THC might hasten the progression of disorder in adolescents who are genetically predisposed to psychotic disorders. However, existing studies must be interpreted with caution because there are other contributing risk factors for psychosis, such as social isolation, that can alter dopamine signaling as well as oligodendrocyte maturation, which can affect myelination in the prefrontal area of the evolving brain. Factors such as increased academic demand can alter the release of cortisol, which in turn affects the dopamine response as well as the structure of the hippocampus as it responds to cortisol. With all of these contributing factors, it is difficult to attribute psychosis in adolescents solely to the use of THC.5

How to discuss cannabis usewith adolescents

Clinicians should engage in open-ended therapeutic conversations about cannabis use with their adolescent patients, including the various types of cannabis and methods of use (ingestion vs inhalation, etc). Educate patients about the acute and long-term effects of THC use, including an increased risk of depression, schizophrenia, and substance abuse in adulthood.

For a patient who has experienced a psychotic episode, early intervention has proven to result in greater treatment response and functional improvement because it reduces brain exposure to neurotoxic effects in adolescents.3 Access to community resources such as school counselors can help to create coping strategies and enhance family support, which can optimize treatment outcomes and medication adherence, all of which will minimize the likelihood of another psychotic episode. Kelleher et al6 found an increased risk of suicidal behavior after a psychotic experience from any cause in adolescents and young adults, and thereby recommended that clinicians conduct continuous assessment of suicidal ideation in such patients.

 

References

1. US Food & Drug Administration. 5 Things to know about delta-8 tetrahydrocannabinol – delta-8 THC. Updated September 14, 2021. Accessed November 3, 2021. https://www.fda.gov/consumers/consumer-updates/5-things-know-about-delta-8-tetrahy drocannabinol-delta-8-thc

2. Patel PK, Leathem LD, Currin DL, et al. Adolescent neurodevelopment and vulnerability to psychosis. Biol Psychiatry. 2021;89(2):184-193. doi: 10.1016/j.biopsych.2020.06.028

3. Kane JM, Robinson DG, Schooler NR, et al. Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE early treatment program. Am J Psychiatry. 2016;173(4):362-372. doi: 10.1176/appi.ajp.2015.15050632

4. Mastrangelo M. Clinical approach to neurodegenerative disorders in childhood: an updated overview. Acta Neurol Belg. 2019;119(4):511-521. doi: 10.1007/s13760-019-01160-0

5. Sewell RA, Ranganathan M, D’Souza DC. Cannabinoids and psychosis. Int Rev Psychiatry. 2009;21(2):152-162. doi: 10.1080/09540260902782802

6. Kelleher I, Cederlöf M, Lichtenstein P. Psychotic experiences as a predictor of the natural course of suicidal ideation: a Swedish cohort study. World Psychiatry. 2014;13(2):184-188. doi: 10.1002/wps.20131

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Dr. Otite is a Research Volunteer, Department of Psychiatry, Jersey Shore University Medical Center, Neptune, New Jersey. Dr. Solanky is a PGY-1 Psychiatry Resident, Department of Psychiatry, Ocean Medical University Center, Brick, New Jersey.

Dr. Doumas is Chief, Child and Adolescent Psychiatry; Residency Program Director; and Vice Chair of Education and Research, Department of Psychiatry, Jersey Shore University Medical Center, Neptune, New Jersey; and Vice Chair, Department of Psychiatry, Hackensack Meridian School of Medicine, Nutley, New Jersey.

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The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

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Dr. Otite is a Research Volunteer, Department of Psychiatry, Jersey Shore University Medical Center, Neptune, New Jersey. Dr. Solanky is a PGY-1 Psychiatry Resident, Department of Psychiatry, Ocean Medical University Center, Brick, New Jersey.

Dr. Doumas is Chief, Child and Adolescent Psychiatry; Residency Program Director; and Vice Chair of Education and Research, Department of Psychiatry, Jersey Shore University Medical Center, Neptune, New Jersey; and Vice Chair, Department of Psychiatry, Hackensack Meridian School of Medicine, Nutley, New Jersey.

Disclosures

The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

Author and Disclosure Information

 

Dr. Otite is a Research Volunteer, Department of Psychiatry, Jersey Shore University Medical Center, Neptune, New Jersey. Dr. Solanky is a PGY-1 Psychiatry Resident, Department of Psychiatry, Ocean Medical University Center, Brick, New Jersey.

Dr. Doumas is Chief, Child and Adolescent Psychiatry; Residency Program Director; and Vice Chair of Education and Research, Department of Psychiatry, Jersey Shore University Medical Center, Neptune, New Jersey; and Vice Chair, Department of Psychiatry, Hackensack Meridian School of Medicine, Nutley, New Jersey.

Disclosures

The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

Article PDF
Article PDF

 

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.
 

Since the recent legalization and decriminalization of cannabis (marijuana) use throughout the United States, adolescents’ access to, and use of, cannabis has increased.1 Cannabis products have been marketed in ways that attract adolescents, such as edible gummies, cookies, and hard candies, as well as by vaping.1 The adolescent years are a delicate period of development during which individuals are prone to psychiatric illness, including depression, anxiety, and psychosis.2,3 Here we discuss the relationship between adolescent cannabis use and the development of psychosis.

How cannabis can affect the adolescent brain

The 2 main psychotropic substances found within the cannabis plant are tetrahydrocannabinol (THC) and cannabidiol (CBD).1,4 Endocannabinoids are fatty acid derivatives produced in the brain that bind to cannabinoid (CB) receptors found in the brain and the peripheral nervous system.1,4

During adolescence, neurodevelopment and neurochemical balances are evolving, and it’s during this period that the bulk of prefrontal pruning occurs, especially in the glutamatergic and gamma aminobutyric acidergic (GABAergic) neural pathways.5 THC affects the CB1 receptors by downregulating the neuron receptors, which then alters the maturation of the prefrontal cortical GABAergic neurons. Also, THC affects the upregulation of the microglia located on the CB2 receptors, thereby altering synaptic pruning even further.2,5

All of these changes can cause brain insults that can contribute to the precipitation of psychotic decompensation in adolescents who ingest products that contain THC. In addition, consuming THC might hasten the progression of disorder in adolescents who are genetically predisposed to psychotic disorders. However, existing studies must be interpreted with caution because there are other contributing risk factors for psychosis, such as social isolation, that can alter dopamine signaling as well as oligodendrocyte maturation, which can affect myelination in the prefrontal area of the evolving brain. Factors such as increased academic demand can alter the release of cortisol, which in turn affects the dopamine response as well as the structure of the hippocampus as it responds to cortisol. With all of these contributing factors, it is difficult to attribute psychosis in adolescents solely to the use of THC.5

How to discuss cannabis usewith adolescents

Clinicians should engage in open-ended therapeutic conversations about cannabis use with their adolescent patients, including the various types of cannabis and methods of use (ingestion vs inhalation, etc). Educate patients about the acute and long-term effects of THC use, including an increased risk of depression, schizophrenia, and substance abuse in adulthood.

For a patient who has experienced a psychotic episode, early intervention has proven to result in greater treatment response and functional improvement because it reduces brain exposure to neurotoxic effects in adolescents.3 Access to community resources such as school counselors can help to create coping strategies and enhance family support, which can optimize treatment outcomes and medication adherence, all of which will minimize the likelihood of another psychotic episode. Kelleher et al6 found an increased risk of suicidal behavior after a psychotic experience from any cause in adolescents and young adults, and thereby recommended that clinicians conduct continuous assessment of suicidal ideation in such patients.

 

 

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.
 

Since the recent legalization and decriminalization of cannabis (marijuana) use throughout the United States, adolescents’ access to, and use of, cannabis has increased.1 Cannabis products have been marketed in ways that attract adolescents, such as edible gummies, cookies, and hard candies, as well as by vaping.1 The adolescent years are a delicate period of development during which individuals are prone to psychiatric illness, including depression, anxiety, and psychosis.2,3 Here we discuss the relationship between adolescent cannabis use and the development of psychosis.

How cannabis can affect the adolescent brain

The 2 main psychotropic substances found within the cannabis plant are tetrahydrocannabinol (THC) and cannabidiol (CBD).1,4 Endocannabinoids are fatty acid derivatives produced in the brain that bind to cannabinoid (CB) receptors found in the brain and the peripheral nervous system.1,4

During adolescence, neurodevelopment and neurochemical balances are evolving, and it’s during this period that the bulk of prefrontal pruning occurs, especially in the glutamatergic and gamma aminobutyric acidergic (GABAergic) neural pathways.5 THC affects the CB1 receptors by downregulating the neuron receptors, which then alters the maturation of the prefrontal cortical GABAergic neurons. Also, THC affects the upregulation of the microglia located on the CB2 receptors, thereby altering synaptic pruning even further.2,5

All of these changes can cause brain insults that can contribute to the precipitation of psychotic decompensation in adolescents who ingest products that contain THC. In addition, consuming THC might hasten the progression of disorder in adolescents who are genetically predisposed to psychotic disorders. However, existing studies must be interpreted with caution because there are other contributing risk factors for psychosis, such as social isolation, that can alter dopamine signaling as well as oligodendrocyte maturation, which can affect myelination in the prefrontal area of the evolving brain. Factors such as increased academic demand can alter the release of cortisol, which in turn affects the dopamine response as well as the structure of the hippocampus as it responds to cortisol. With all of these contributing factors, it is difficult to attribute psychosis in adolescents solely to the use of THC.5

How to discuss cannabis usewith adolescents

Clinicians should engage in open-ended therapeutic conversations about cannabis use with their adolescent patients, including the various types of cannabis and methods of use (ingestion vs inhalation, etc). Educate patients about the acute and long-term effects of THC use, including an increased risk of depression, schizophrenia, and substance abuse in adulthood.

For a patient who has experienced a psychotic episode, early intervention has proven to result in greater treatment response and functional improvement because it reduces brain exposure to neurotoxic effects in adolescents.3 Access to community resources such as school counselors can help to create coping strategies and enhance family support, which can optimize treatment outcomes and medication adherence, all of which will minimize the likelihood of another psychotic episode. Kelleher et al6 found an increased risk of suicidal behavior after a psychotic experience from any cause in adolescents and young adults, and thereby recommended that clinicians conduct continuous assessment of suicidal ideation in such patients.

 

References

1. US Food & Drug Administration. 5 Things to know about delta-8 tetrahydrocannabinol – delta-8 THC. Updated September 14, 2021. Accessed November 3, 2021. https://www.fda.gov/consumers/consumer-updates/5-things-know-about-delta-8-tetrahy drocannabinol-delta-8-thc

2. Patel PK, Leathem LD, Currin DL, et al. Adolescent neurodevelopment and vulnerability to psychosis. Biol Psychiatry. 2021;89(2):184-193. doi: 10.1016/j.biopsych.2020.06.028

3. Kane JM, Robinson DG, Schooler NR, et al. Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE early treatment program. Am J Psychiatry. 2016;173(4):362-372. doi: 10.1176/appi.ajp.2015.15050632

4. Mastrangelo M. Clinical approach to neurodegenerative disorders in childhood: an updated overview. Acta Neurol Belg. 2019;119(4):511-521. doi: 10.1007/s13760-019-01160-0

5. Sewell RA, Ranganathan M, D’Souza DC. Cannabinoids and psychosis. Int Rev Psychiatry. 2009;21(2):152-162. doi: 10.1080/09540260902782802

6. Kelleher I, Cederlöf M, Lichtenstein P. Psychotic experiences as a predictor of the natural course of suicidal ideation: a Swedish cohort study. World Psychiatry. 2014;13(2):184-188. doi: 10.1002/wps.20131

References

1. US Food & Drug Administration. 5 Things to know about delta-8 tetrahydrocannabinol – delta-8 THC. Updated September 14, 2021. Accessed November 3, 2021. https://www.fda.gov/consumers/consumer-updates/5-things-know-about-delta-8-tetrahy drocannabinol-delta-8-thc

2. Patel PK, Leathem LD, Currin DL, et al. Adolescent neurodevelopment and vulnerability to psychosis. Biol Psychiatry. 2021;89(2):184-193. doi: 10.1016/j.biopsych.2020.06.028

3. Kane JM, Robinson DG, Schooler NR, et al. Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE early treatment program. Am J Psychiatry. 2016;173(4):362-372. doi: 10.1176/appi.ajp.2015.15050632

4. Mastrangelo M. Clinical approach to neurodegenerative disorders in childhood: an updated overview. Acta Neurol Belg. 2019;119(4):511-521. doi: 10.1007/s13760-019-01160-0

5. Sewell RA, Ranganathan M, D’Souza DC. Cannabinoids and psychosis. Int Rev Psychiatry. 2009;21(2):152-162. doi: 10.1080/09540260902782802

6. Kelleher I, Cederlöf M, Lichtenstein P. Psychotic experiences as a predictor of the natural course of suicidal ideation: a Swedish cohort study. World Psychiatry. 2014;13(2):184-188. doi: 10.1002/wps.20131

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HCV screening in pregnancy: Reducing the risk for casualties in the quest for elimination

Article Type
Changed
Tue, 11/23/2021 - 14:10

Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

  • Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
  • Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
  • Be aware that intrahepatic is more common with HCV.
  • Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

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Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

  • Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
  • Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
  • Be aware that intrahepatic is more common with HCV.
  • Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Because hepatitis C virus (HCV) infection is typically asymptomatic, its presence can easily be overlooked without appropriate screening efforts. For those screening efforts to be effective, they must keep pace with the changing demographic face of this increasingly prevalent but treatable disease.

Perhaps the most dramatic shift in HCV demographics in recent years has been the increase of infections among those born after 1965, a trend primarily driven by the opioid epidemic. In addition, data from the National Notifiable Diseases Surveillance System show that cases of diagnosed HCV doubled among women of childbearing age from 2006 to 2014, with new infections in younger women surpassing those in older age groups.

With such trends in mind, the Centers for Disease Control and Prevention broadened their recommendations regarding HCV in 2020 to include one-time testing in all adults aged 18 years and older and screening of all pregnant women during each pregnancy, except where the prevalence of infection is less than 0.1%, a threshold that no state has yet achieved.

The US Preventive Services Task Force (USPSTF) subsequently followed suit in their own recommendations.

The American Association for the Study of Liver Diseases/Infectious Diseases Society of America have long advocated for extensive expansion in their screening recommendations for HCV, including pregnancy.

Although the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine did not immediately adopt these recommendations, they have since endorsed them in May 2021 and June 2021, respectively.
 

The hepatologist perspective

As a practicing hepatologist, this seems like an uncontroversial recommendation. Obstetricians already screen for hepatitis B virus in each pregnancy. It should be easy to add HCV testing to the same lab testing.

Risk-based screening has repeatedly been demonstrated to be ineffective. It should be easier to test all women than to ask prying questions about high-risk behaviors.

Given the increase of injection drug use and resultant HCV infections in women of childbearing age, this seems like a perfect opportunity to identify chronically infected women and counsel them on transmission and cure. And pregnancy is also unique in that it is a time of near-universal health coverage.

Let’s address some of the operational issues.

The diagnostic cascade for HCV can be made very easy. HCV antibody testing is our standard screening test and, when positive, can automatically reflex to HCV polymerase chain reaction (PCR), the diagnostic test. Thus, with one blood sample, you can both screen for and diagnose infection.

Current guidelines do not recommend treating HCV during pregnancy, although therapy can be considered on an individual basis. Linkage to a knowledgeable provider who can discuss transmission and treatment, as well as assess the stage of liver injury, should decrease the burden on the ob.gyn.

The impact on pregnancy is marginal. HCV should not change either the mode of delivery or the decision to breastfeed. The AASLD/IDSA guidance outlines only four recommendations for monitoring during pregnancy:

  • Obtain HCV RNA to see whether the infection is active and assess liver function at initiation of prenatal care.
  • Prenatal care should be tailored to the pregnancy. There is no modification recommended to decrease mother-to-child transmission (MTCT).
  • Be aware that intrahepatic is more common with HCV.
  • Women with have a higher rate of adverse outcomes and should be linked to a high-risk obstetrics specialist.

But of course, what seems easy to one specialist may not be true of another. With that in mind, let’s hear the ob.gyn. perspective on these updated screening recommendations.
 

The ob.gyn. perspective

Recent guidelines from the CDC, ACOG, and SMFM recommend universal screening for HCV in all pregnant women. The increased availability of highly effective antiviral regimens makes universal screening a logical strategy, especially to identify candidates for this curative treatment. What is questionable, however, is the recommended timing by which this screening should take place.

HCV screening during pregnancy, as currently recommended, provides no immediate benefit for the pregnant woman or the fetus/neonate, given that antiviral treatments have not been approved during gestation, and there are no known measures that decrease MTCT or change routine perinatal care.

We also must not forget that a significant proportion of women in the United States, particularly those with limited resources, do not receive prenatal care at all. Most of them, however, will present to a hospital for delivery. Consequently, compliance with screening might be higher if performed at the time of delivery rather than antepartum.

Deferring screening until the intrapartum or immediate postpartum period, at least until antiviral treatment during pregnancy becomes a reality, was discussed. The rationale was that this approach might obviate the need to deal with the unintended consequences and burden of testing for HCV during pregnancy. Ultimately, ACOG and SMFM fell in line with the CDC recommendations.

Despite the lack of robust evidence regarding the risk for MTCT associated with commonly performed obstetric procedures (for example, genetic amniocentesis, artificial rupture of the membranes during labor, placement of an intrauterine pressure catheter), clinicians may be reluctant to perform them in HCV-infected women, resulting in potential deviations from the obstetric standard of care.

Similarly, it is likely that patients may choose to have a cesarean delivery for the sole purpose of decreasing MTCT, despite the lack of evidence for this. Such ill-advised patient-driven decisions are increasingly likely in the current environment, where social media can rapidly disseminate misinformation.
 

Implications for pediatric patients

One cannot isolate HCV screening in pregnancy from the consequences that may potentially occur as part of the infant’s transition to the care of a pediatrician.

Even though MTCT is estimated to occur in just 5%-15% of cases, all children born to HCV viremic mothers should be screened for HCV.

Traditionally, screening for HCV antibodies occurred after 18 months of age. In those who test positive, HCV PCR testing is recommended at 3 years. However, this algorithm is being called into question because only approximately one-third of infants are successfully screened.

HCV RNA testing in the first year after birth has been suggested. However, even proponents of this approach concur that all management decisions should be deferred until after the age of 3 years, when medications are approved for pediatric use.

In addition, HCV testing would be required again before considering therapy because children have higher rates of spontaneous clearance.
 

Seeking consensus beyond the controversy

Controversy remains surrounding the most recent update to the HCV screening guidelines. The current recommendation to screen during pregnancy cannot modify the risk for MTCT, has no impact on decisions regarding mode of delivery or breastfeeding, and could potentially cause harm by making obstetricians defer necessary invasive procedures even though there are no data linking them to an increase in MTCT.

Yet after extensive debate, the CDC, USPSTF, AASLD/IDSA, ACOG, and SMFM all developed their current recommendations to initiate HCV screening during pregnancy. To make this successful, screening algorithms need to be simple and consistent across all society recommendations.

HCV antibody testing should always reflex to the diagnostic test (HCV PCR) to allow confirmation in those who test positive without requiring an additional blood test. Viremic mothers (those who are HCV positive on PCR) should be linked to a provider who can discuss prognosis, transmission, and treatment. The importance of screening the infant also must be communicated to the parents and pediatrician alike.

Dr. Reau has served as a director, officer, partner, employee, adviser, consultant, or trustee for AbbVie, Gilead, Arbutus, Intercept, and Salix; received research grants from AbbVie and Gilead; and received income from AASLD. Dr. Pacheco disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

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Lessons in perinatal psychiatry after 19 months of COVID-19*

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Tue, 01/11/2022 - 11:21

For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.

In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.

Dr. Lee S. Cohen

Telemedicine

Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.

COVID-19 vaccines in pregnancy

We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.

Bipolar disorder

Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.

Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).

The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.

We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.

What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
 

 

 

Anxiety

Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.

Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.

Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.

Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
 

Insomnia

For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.

Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
 

Postpartum psychosis

It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.

The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.

While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.

Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.

*This column was updated on Jan. 11. 2022.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.

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For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.

In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.

Dr. Lee S. Cohen

Telemedicine

Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.

COVID-19 vaccines in pregnancy

We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.

Bipolar disorder

Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.

Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).

The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.

We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.

What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
 

 

 

Anxiety

Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.

Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.

Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.

Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
 

Insomnia

For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.

Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
 

Postpartum psychosis

It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.

The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.

While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.

Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.

*This column was updated on Jan. 11. 2022.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.

For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.

In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.

Dr. Lee S. Cohen

Telemedicine

Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.

COVID-19 vaccines in pregnancy

We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.

Bipolar disorder

Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.

Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).

The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.

We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.

What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
 

 

 

Anxiety

Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.

Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.

Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.

Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
 

Insomnia

For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.

Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
 

Postpartum psychosis

It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.

The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.

While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.

Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.

*This column was updated on Jan. 11. 2022.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.

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When should psychiatrists retire?

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Mon, 11/22/2021 - 09:26

I remember a conversation I had at the end of my training with an older psychiatrist who was closing his practice. I was very excited to finally be a psychiatrist, and therefore a bit shocked that someone would voluntarily end a career I was just beginning. After all, psychiatry is a field where people can practice with flexibility, and a private practice is not an all-or-none endeavor.

Dr. Dinah Miller

“Dinah,” this gentleman said to me, sensing my dismay, “I’m 74. I’m allowed to retire.”

Like many retired psychiatrists, this one continued to come to grand rounds every Monday, dressed in a suit, which was followed by lunch with friends in the dining room. He continued to be involved in professional activities and lived to be 96.

Another dear friend practiced psychiatry until she entered hospice after a 2-year battle with cancer. Others have whittled down their practices, hanging on to a few hours of patient care along with supervision, teaching, and involvement with professional organizations.

In discussing retirement with some of my peers, it’s become immediately clear that each psychiatrist approaches this decision – and how they choose to live after it’s made – with a unique set of concerns and goals.
 

Fatigued by bureaucracy

Robin Weiss, MD, is in the process of “shrinking” her private practice. She is quick to say she is not retiring, but planning to scale back to 1 day a week starting next summer.

“I want to work less so I have more time for my grandchildren, friends, and travel, and to finally write more.” She also hopes to improve her ping-pong game and exercise habits.

“I’m so tired of prior authorizations, and the one day a week of patients I’ve been committed to feels just about right.”

During the pandemic, Dr. Weiss relinquished her office and she plans to continue with a virtual practice, which allows her more flexibility in terms of where she is physically located.

“The pandemic didn’t influence my decision to scale back, but it did play a role in deciding to give up my office,” she said.


A decision precipitated by medical reasons

Stephen Warres, MD, is a child and adolescent psychiatrist in Maryland who fully retired from practice in June 2021. He started scaling back a few years ago, when he had to give up his office because the building was undergoing renovations.

“I was seeing some patients from my home, but for 2 years I had been working 1 or 2 weekends a month at the Baltimore city jail, and I thought of that as my final act. It was a setting I had never worked in, and I left there 4 months before the pandemic started.”

Dr. Warres noted that his decision to retire was propelled by his diagnosis of Parkinson’s disease at the end of 2019.

“So far I only have a resting tremor, but this is an illness in which cognitive decline is a possibility.”
 

 

 

The emotional roller-coaster that can await

Dr. Warres said a myriad of emotions come with retirement, beginning with a sense of guilt.

“Why am I leaving when others practice longer? I read about a psychiatrist in California who was still practicing when he died at 102. And the last patient whom I saw when I left practice was a man I started treating just 2 days after I started residency in 1976! When I told him I would be retiring, he found a new psychiatrist who is 82 years old.”

This was followed, he said, by a sense of shame.

“My father was a radiologist and he retired at 76, the same age that I am now, but he volunteered 2 days a week for the state attorney’s office until he was 92, and I’m not doing that.”

What Dr. Warres is choosing to do instead is indulge his many interests, including reading; writing; and practicing on the instrument he’s recently taken up, the harmonium.

This cascade of emotions led to one that was arguably more pleasurable: a sense of immense relief.

“When I got my first request after retirement for a prior authorization, I felt jubilant, like I wanted to throw a party! I felt like I had been walking with a backpack full of weights, and only after the weights were removed did I realize how much lighter it was.

“I loved doing psychotherapy, but more and more psychiatry was not what I had signed up for. I’m relieved that I no longer have to keep up with psychopharmacology. In a way, the Parkinson’s diagnosis sealed the deal. I felt that it gave me license, like a get out of jail card, to retire.”

But even this sense of palpable relief hasn’t closed the cycle of emotions Dr. Warres is experiencing over his retirement.

“You know, the more relieved I am, the more guilt I feel.”
 

As intellectually adventurous as ever

Marshal Folstein, MD, of Miami retired over a decade ago after a long academic career at Johns Hopkins University, Baltimore, and as chairman of psychiatry at Tufts University, Boston. His Facebook profile states: “Leading the quiet life of a retired professor.”

He said retirement was an easy decision for he and his wife Susan, herself a former academic psychiatrist, which allowed them to immediately change gears.

“At the beginning, we traveled a bit. I wanted to continue with music, so I took flute lessons, and then I played flute in my synagogue, so now I have recently retired from that. I spend my time reading Talmud and the Bible and I keep asking questions. I found a new group of people, some are physicians, and we study and argue. I just turned 80 and I’m intellectually busy and happy.”


The retirement coach

Barbara Fowler, PhD, is a lifespan services consultant at Johns Hopkins who works with faculty and staff getting ready to retire. She said that the university has methods in place to make this decision less jarring.

“The school of medicine has a faculty transition plan that lets people cut back over a set period of time while still keeping benefits. It gives doctors a way to wind up their research and clinical responsibilities, and this is negotiated on an individual level.”

When she’s discussing with someone the possibility of retirement, Dr. Fowler likes to begin by asking them to define what exactly they mean by that word.

“The stereotyped concept is that someone stops what they are doing completely and spends their time playing golf or canasta,” she said. “But the baby boomers are redefining that. Physicians often continue to see some patients or participate in professional organizations. Some people are happy to stop doing the work they have done for years and go do something different, whereas others are interested in scaling back on work activities while adding new ones.”
 

Timing it right

So, when should psychiatrists retire? The most obvious time to reconsider is when the doctor is no longer able to perform work-related obligations owing to physical or cognitive limitations.

Financial constraints are another factor that comes into play. How necessary is it to work to pay the bills?

“When the kids are out of college and the mortgage is paid off, then there may be the financial means to reconceptualize work life and how you want to rebuild it,” Dr. Fowler said. “Because whether or not people are getting paid, they want to be productive.”

For some, this may come in the form of working in a reduced capacity. Certain practices are more amenable to part-time work or a gradual decrease in hours. A private practice may allow for more control than a position with an institution where an employee may have to continue working full time or not at all.

For others, that productivity might be measured in pursuing their own interests or assisting with family members who need their help. Grandchildren can be an important factor, especially if they live at a distance or childcare is needed. These issues became all the more salient when the pandemic shuttered day care centers and schools, and people limited contact with those outside their households.

Retirement for all physicians is wrapped in issues of identity; for those who have not cultivated other interests, retirement can be a huge loss with no clear path forward. And in an environment where there is a psychiatrist shortage, health care workers are deemed heroes, and human distress is mounting, retirement may come with mixed feelings of guilt, even when the psychiatrist wants a change and is ready for the next chapter. Finally, for those who have launched programs or research projects, there may be the fear that there is no one else who can or will carry on, and that all will be lost.

Yet these considerations focus on the negative, whereas Dr. Fowler said she likes to frame retirement in a positive light. “The key is having more choices; looking for activities that inspire passion; and asking, how can you live your best life?”

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. A version of this article first appeared on Medscape.com.

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I remember a conversation I had at the end of my training with an older psychiatrist who was closing his practice. I was very excited to finally be a psychiatrist, and therefore a bit shocked that someone would voluntarily end a career I was just beginning. After all, psychiatry is a field where people can practice with flexibility, and a private practice is not an all-or-none endeavor.

Dr. Dinah Miller

“Dinah,” this gentleman said to me, sensing my dismay, “I’m 74. I’m allowed to retire.”

Like many retired psychiatrists, this one continued to come to grand rounds every Monday, dressed in a suit, which was followed by lunch with friends in the dining room. He continued to be involved in professional activities and lived to be 96.

Another dear friend practiced psychiatry until she entered hospice after a 2-year battle with cancer. Others have whittled down their practices, hanging on to a few hours of patient care along with supervision, teaching, and involvement with professional organizations.

In discussing retirement with some of my peers, it’s become immediately clear that each psychiatrist approaches this decision – and how they choose to live after it’s made – with a unique set of concerns and goals.
 

Fatigued by bureaucracy

Robin Weiss, MD, is in the process of “shrinking” her private practice. She is quick to say she is not retiring, but planning to scale back to 1 day a week starting next summer.

“I want to work less so I have more time for my grandchildren, friends, and travel, and to finally write more.” She also hopes to improve her ping-pong game and exercise habits.

“I’m so tired of prior authorizations, and the one day a week of patients I’ve been committed to feels just about right.”

During the pandemic, Dr. Weiss relinquished her office and she plans to continue with a virtual practice, which allows her more flexibility in terms of where she is physically located.

“The pandemic didn’t influence my decision to scale back, but it did play a role in deciding to give up my office,” she said.


A decision precipitated by medical reasons

Stephen Warres, MD, is a child and adolescent psychiatrist in Maryland who fully retired from practice in June 2021. He started scaling back a few years ago, when he had to give up his office because the building was undergoing renovations.

“I was seeing some patients from my home, but for 2 years I had been working 1 or 2 weekends a month at the Baltimore city jail, and I thought of that as my final act. It was a setting I had never worked in, and I left there 4 months before the pandemic started.”

Dr. Warres noted that his decision to retire was propelled by his diagnosis of Parkinson’s disease at the end of 2019.

“So far I only have a resting tremor, but this is an illness in which cognitive decline is a possibility.”
 

 

 

The emotional roller-coaster that can await

Dr. Warres said a myriad of emotions come with retirement, beginning with a sense of guilt.

“Why am I leaving when others practice longer? I read about a psychiatrist in California who was still practicing when he died at 102. And the last patient whom I saw when I left practice was a man I started treating just 2 days after I started residency in 1976! When I told him I would be retiring, he found a new psychiatrist who is 82 years old.”

This was followed, he said, by a sense of shame.

“My father was a radiologist and he retired at 76, the same age that I am now, but he volunteered 2 days a week for the state attorney’s office until he was 92, and I’m not doing that.”

What Dr. Warres is choosing to do instead is indulge his many interests, including reading; writing; and practicing on the instrument he’s recently taken up, the harmonium.

This cascade of emotions led to one that was arguably more pleasurable: a sense of immense relief.

“When I got my first request after retirement for a prior authorization, I felt jubilant, like I wanted to throw a party! I felt like I had been walking with a backpack full of weights, and only after the weights were removed did I realize how much lighter it was.

“I loved doing psychotherapy, but more and more psychiatry was not what I had signed up for. I’m relieved that I no longer have to keep up with psychopharmacology. In a way, the Parkinson’s diagnosis sealed the deal. I felt that it gave me license, like a get out of jail card, to retire.”

But even this sense of palpable relief hasn’t closed the cycle of emotions Dr. Warres is experiencing over his retirement.

“You know, the more relieved I am, the more guilt I feel.”
 

As intellectually adventurous as ever

Marshal Folstein, MD, of Miami retired over a decade ago after a long academic career at Johns Hopkins University, Baltimore, and as chairman of psychiatry at Tufts University, Boston. His Facebook profile states: “Leading the quiet life of a retired professor.”

He said retirement was an easy decision for he and his wife Susan, herself a former academic psychiatrist, which allowed them to immediately change gears.

“At the beginning, we traveled a bit. I wanted to continue with music, so I took flute lessons, and then I played flute in my synagogue, so now I have recently retired from that. I spend my time reading Talmud and the Bible and I keep asking questions. I found a new group of people, some are physicians, and we study and argue. I just turned 80 and I’m intellectually busy and happy.”


The retirement coach

Barbara Fowler, PhD, is a lifespan services consultant at Johns Hopkins who works with faculty and staff getting ready to retire. She said that the university has methods in place to make this decision less jarring.

“The school of medicine has a faculty transition plan that lets people cut back over a set period of time while still keeping benefits. It gives doctors a way to wind up their research and clinical responsibilities, and this is negotiated on an individual level.”

When she’s discussing with someone the possibility of retirement, Dr. Fowler likes to begin by asking them to define what exactly they mean by that word.

“The stereotyped concept is that someone stops what they are doing completely and spends their time playing golf or canasta,” she said. “But the baby boomers are redefining that. Physicians often continue to see some patients or participate in professional organizations. Some people are happy to stop doing the work they have done for years and go do something different, whereas others are interested in scaling back on work activities while adding new ones.”
 

Timing it right

So, when should psychiatrists retire? The most obvious time to reconsider is when the doctor is no longer able to perform work-related obligations owing to physical or cognitive limitations.

Financial constraints are another factor that comes into play. How necessary is it to work to pay the bills?

“When the kids are out of college and the mortgage is paid off, then there may be the financial means to reconceptualize work life and how you want to rebuild it,” Dr. Fowler said. “Because whether or not people are getting paid, they want to be productive.”

For some, this may come in the form of working in a reduced capacity. Certain practices are more amenable to part-time work or a gradual decrease in hours. A private practice may allow for more control than a position with an institution where an employee may have to continue working full time or not at all.

For others, that productivity might be measured in pursuing their own interests or assisting with family members who need their help. Grandchildren can be an important factor, especially if they live at a distance or childcare is needed. These issues became all the more salient when the pandemic shuttered day care centers and schools, and people limited contact with those outside their households.

Retirement for all physicians is wrapped in issues of identity; for those who have not cultivated other interests, retirement can be a huge loss with no clear path forward. And in an environment where there is a psychiatrist shortage, health care workers are deemed heroes, and human distress is mounting, retirement may come with mixed feelings of guilt, even when the psychiatrist wants a change and is ready for the next chapter. Finally, for those who have launched programs or research projects, there may be the fear that there is no one else who can or will carry on, and that all will be lost.

Yet these considerations focus on the negative, whereas Dr. Fowler said she likes to frame retirement in a positive light. “The key is having more choices; looking for activities that inspire passion; and asking, how can you live your best life?”

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. A version of this article first appeared on Medscape.com.

I remember a conversation I had at the end of my training with an older psychiatrist who was closing his practice. I was very excited to finally be a psychiatrist, and therefore a bit shocked that someone would voluntarily end a career I was just beginning. After all, psychiatry is a field where people can practice with flexibility, and a private practice is not an all-or-none endeavor.

Dr. Dinah Miller

“Dinah,” this gentleman said to me, sensing my dismay, “I’m 74. I’m allowed to retire.”

Like many retired psychiatrists, this one continued to come to grand rounds every Monday, dressed in a suit, which was followed by lunch with friends in the dining room. He continued to be involved in professional activities and lived to be 96.

Another dear friend practiced psychiatry until she entered hospice after a 2-year battle with cancer. Others have whittled down their practices, hanging on to a few hours of patient care along with supervision, teaching, and involvement with professional organizations.

In discussing retirement with some of my peers, it’s become immediately clear that each psychiatrist approaches this decision – and how they choose to live after it’s made – with a unique set of concerns and goals.
 

Fatigued by bureaucracy

Robin Weiss, MD, is in the process of “shrinking” her private practice. She is quick to say she is not retiring, but planning to scale back to 1 day a week starting next summer.

“I want to work less so I have more time for my grandchildren, friends, and travel, and to finally write more.” She also hopes to improve her ping-pong game and exercise habits.

“I’m so tired of prior authorizations, and the one day a week of patients I’ve been committed to feels just about right.”

During the pandemic, Dr. Weiss relinquished her office and she plans to continue with a virtual practice, which allows her more flexibility in terms of where she is physically located.

“The pandemic didn’t influence my decision to scale back, but it did play a role in deciding to give up my office,” she said.


A decision precipitated by medical reasons

Stephen Warres, MD, is a child and adolescent psychiatrist in Maryland who fully retired from practice in June 2021. He started scaling back a few years ago, when he had to give up his office because the building was undergoing renovations.

“I was seeing some patients from my home, but for 2 years I had been working 1 or 2 weekends a month at the Baltimore city jail, and I thought of that as my final act. It was a setting I had never worked in, and I left there 4 months before the pandemic started.”

Dr. Warres noted that his decision to retire was propelled by his diagnosis of Parkinson’s disease at the end of 2019.

“So far I only have a resting tremor, but this is an illness in which cognitive decline is a possibility.”
 

 

 

The emotional roller-coaster that can await

Dr. Warres said a myriad of emotions come with retirement, beginning with a sense of guilt.

“Why am I leaving when others practice longer? I read about a psychiatrist in California who was still practicing when he died at 102. And the last patient whom I saw when I left practice was a man I started treating just 2 days after I started residency in 1976! When I told him I would be retiring, he found a new psychiatrist who is 82 years old.”

This was followed, he said, by a sense of shame.

“My father was a radiologist and he retired at 76, the same age that I am now, but he volunteered 2 days a week for the state attorney’s office until he was 92, and I’m not doing that.”

What Dr. Warres is choosing to do instead is indulge his many interests, including reading; writing; and practicing on the instrument he’s recently taken up, the harmonium.

This cascade of emotions led to one that was arguably more pleasurable: a sense of immense relief.

“When I got my first request after retirement for a prior authorization, I felt jubilant, like I wanted to throw a party! I felt like I had been walking with a backpack full of weights, and only after the weights were removed did I realize how much lighter it was.

“I loved doing psychotherapy, but more and more psychiatry was not what I had signed up for. I’m relieved that I no longer have to keep up with psychopharmacology. In a way, the Parkinson’s diagnosis sealed the deal. I felt that it gave me license, like a get out of jail card, to retire.”

But even this sense of palpable relief hasn’t closed the cycle of emotions Dr. Warres is experiencing over his retirement.

“You know, the more relieved I am, the more guilt I feel.”
 

As intellectually adventurous as ever

Marshal Folstein, MD, of Miami retired over a decade ago after a long academic career at Johns Hopkins University, Baltimore, and as chairman of psychiatry at Tufts University, Boston. His Facebook profile states: “Leading the quiet life of a retired professor.”

He said retirement was an easy decision for he and his wife Susan, herself a former academic psychiatrist, which allowed them to immediately change gears.

“At the beginning, we traveled a bit. I wanted to continue with music, so I took flute lessons, and then I played flute in my synagogue, so now I have recently retired from that. I spend my time reading Talmud and the Bible and I keep asking questions. I found a new group of people, some are physicians, and we study and argue. I just turned 80 and I’m intellectually busy and happy.”


The retirement coach

Barbara Fowler, PhD, is a lifespan services consultant at Johns Hopkins who works with faculty and staff getting ready to retire. She said that the university has methods in place to make this decision less jarring.

“The school of medicine has a faculty transition plan that lets people cut back over a set period of time while still keeping benefits. It gives doctors a way to wind up their research and clinical responsibilities, and this is negotiated on an individual level.”

When she’s discussing with someone the possibility of retirement, Dr. Fowler likes to begin by asking them to define what exactly they mean by that word.

“The stereotyped concept is that someone stops what they are doing completely and spends their time playing golf or canasta,” she said. “But the baby boomers are redefining that. Physicians often continue to see some patients or participate in professional organizations. Some people are happy to stop doing the work they have done for years and go do something different, whereas others are interested in scaling back on work activities while adding new ones.”
 

Timing it right

So, when should psychiatrists retire? The most obvious time to reconsider is when the doctor is no longer able to perform work-related obligations owing to physical or cognitive limitations.

Financial constraints are another factor that comes into play. How necessary is it to work to pay the bills?

“When the kids are out of college and the mortgage is paid off, then there may be the financial means to reconceptualize work life and how you want to rebuild it,” Dr. Fowler said. “Because whether or not people are getting paid, they want to be productive.”

For some, this may come in the form of working in a reduced capacity. Certain practices are more amenable to part-time work or a gradual decrease in hours. A private practice may allow for more control than a position with an institution where an employee may have to continue working full time or not at all.

For others, that productivity might be measured in pursuing their own interests or assisting with family members who need their help. Grandchildren can be an important factor, especially if they live at a distance or childcare is needed. These issues became all the more salient when the pandemic shuttered day care centers and schools, and people limited contact with those outside their households.

Retirement for all physicians is wrapped in issues of identity; for those who have not cultivated other interests, retirement can be a huge loss with no clear path forward. And in an environment where there is a psychiatrist shortage, health care workers are deemed heroes, and human distress is mounting, retirement may come with mixed feelings of guilt, even when the psychiatrist wants a change and is ready for the next chapter. Finally, for those who have launched programs or research projects, there may be the fear that there is no one else who can or will carry on, and that all will be lost.

Yet these considerations focus on the negative, whereas Dr. Fowler said she likes to frame retirement in a positive light. “The key is having more choices; looking for activities that inspire passion; and asking, how can you live your best life?”

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. A version of this article first appeared on Medscape.com.

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