Mental Health

U.K. scientists show it is possible to spot signs of brain impairment in patients as early as 9 years before they receive a diagnosis of dementia, offering hope for interventions to reduce the risk of the disease developing.

To date it has been unclear whether it might be possible to detect changes in brain function before the onset of symptoms, so researchers at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust set out to determine whether people who developed a range of neurodegenerative diagnoses demonstrated reduced cognitive function at their baseline assessment.

The authors explained: “The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, prediagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease.”
 

Prediagnostic cognitive and functional impairment identified

The researchers analyzed data from the UK Biobank and compared cognitive and functional measures, including problem solving, memory, reaction times and grip strength, as well as data on weight loss and gain and on the number of falls, in individuals who subsequently developed a number of dementia-related diseases (Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy), with those who did not have a neurodegenerative diagnosis. After adjustment for the effects of age, the same measures were regressed against time to diagnosis. The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The researchers found evidence of prediagnostic cognitive impairment and decline with time, particularly in Alzheimer’s disease where those who went on to develop the disease scored more poorly compared with healthy individuals when it came to problem solving tasks, reaction times, remembering lists of numbers, prospective memory, and pair matching. This was also the case for people who developed frontotemporal dementia, the authors said.

Nol Swaddiwudhipong, MB, of the University of Cambridge, and first author, said: “When we looked back at patients’ histories, it became clear that they were showing some cognitive impairment several years before their symptoms became obvious enough to prompt a diagnosis. The impairments were often subtle, but across a number of aspects of cognition.”

Prediagnostic functional impairment and decline was also observed in multiple diseases, the authors said. People who went on to develop Alzheimer’s disease were more likely than were healthy adults to have had a fall in the previous 12 months, with those patients who went on to develop progressive supranuclear palsy (PSP) being more than twice as likely as healthy individuals to have had a fall.

The time between baseline assessment and diagnosis varied between 4.7 years for dementia with Lewy bodies and 8.3 years for Alzheimer’s disease.

“For every condition studied – including Parkinson’s disease and dementia with Lewy bodies – patients reported poorer overall health at baseline,” said the authors.
 

Potential for new treatments

The study findings that cognitive and functional decline occurs “years before symptoms become obvious” in multiple neurodegenerative diseases, raises the possibility that in the future at-risk patients could be screened to help select those who would benefit from interventions to reduce their risk of developing one of the conditions, or to help identify patients suitable for recruitment to clinical trials for new treatments.

Dr Swaddiwudhipong emphasized: “This is a step towards us being able to screen people who are at greatest risk – for example, people over 50 or those who have high blood pressure or do not do enough exercise – and intervene at an earlier stage to help them reduce their risk.”

There are currently very few effective treatments for dementia or other forms of neurodegeneration, the authors pointed out, in part because these conditions are often only diagnosed once symptoms appear, whereas the underlying neurodegeneration may have “begun years, even decades, earlier.” This means that by the time patients take part in clinical trials, it may already be too late in the disease process to alter its course, they explained.

Timothy Rittman, BMBS, PhD, department of clinical neurosciences, University of Cambridge, and senior author, explained that the findings could also help identify people who can participate in clinical trials for potential new treatments. “The problem with clinical trials is that by necessity they often recruit patients with a diagnosis, but we know that by this point they are already some way down the road and their condition cannot be stopped. If we can find these individuals early enough, we’ll have a better chance of seeing if the drugs are effective,” he emphasized.

Commenting on the new research, Richard Oakley, PhD, associate director of research at Alzheimer’s Society, said: “Studies like this show the importance in continued investment in dementia research to revolutionize diagnosis and drive new treatments, so one day we will beat dementia.”

The research was funded by the Medical Research Council with support from the NIHR Cambridge Biomedical Research Centre. The authors reported no conflicts of interest.

A version of this article first appeared on Medscape UK.

U.K. scientists show it is possible to spot signs of brain impairment in patients as early as 9 years before they receive a diagnosis of dementia, offering hope for interventions to reduce the risk of the disease developing.

To date it has been unclear whether it might be possible to detect changes in brain function before the onset of symptoms, so researchers at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust set out to determine whether people who developed a range of neurodegenerative diagnoses demonstrated reduced cognitive function at their baseline assessment.

The authors explained: “The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, prediagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease.”
 

Prediagnostic cognitive and functional impairment identified

The researchers analyzed data from the UK Biobank and compared cognitive and functional measures, including problem solving, memory, reaction times and grip strength, as well as data on weight loss and gain and on the number of falls, in individuals who subsequently developed a number of dementia-related diseases (Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy), with those who did not have a neurodegenerative diagnosis. After adjustment for the effects of age, the same measures were regressed against time to diagnosis. The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The researchers found evidence of prediagnostic cognitive impairment and decline with time, particularly in Alzheimer’s disease where those who went on to develop the disease scored more poorly compared with healthy individuals when it came to problem solving tasks, reaction times, remembering lists of numbers, prospective memory, and pair matching. This was also the case for people who developed frontotemporal dementia, the authors said.

Nol Swaddiwudhipong, MB, of the University of Cambridge, and first author, said: “When we looked back at patients’ histories, it became clear that they were showing some cognitive impairment several years before their symptoms became obvious enough to prompt a diagnosis. The impairments were often subtle, but across a number of aspects of cognition.”

Prediagnostic functional impairment and decline was also observed in multiple diseases, the authors said. People who went on to develop Alzheimer’s disease were more likely than were healthy adults to have had a fall in the previous 12 months, with those patients who went on to develop progressive supranuclear palsy (PSP) being more than twice as likely as healthy individuals to have had a fall.

The time between baseline assessment and diagnosis varied between 4.7 years for dementia with Lewy bodies and 8.3 years for Alzheimer’s disease.

“For every condition studied – including Parkinson’s disease and dementia with Lewy bodies – patients reported poorer overall health at baseline,” said the authors.
 

Potential for new treatments

The study findings that cognitive and functional decline occurs “years before symptoms become obvious” in multiple neurodegenerative diseases, raises the possibility that in the future at-risk patients could be screened to help select those who would benefit from interventions to reduce their risk of developing one of the conditions, or to help identify patients suitable for recruitment to clinical trials for new treatments.

Dr Swaddiwudhipong emphasized: “This is a step towards us being able to screen people who are at greatest risk – for example, people over 50 or those who have high blood pressure or do not do enough exercise – and intervene at an earlier stage to help them reduce their risk.”

There are currently very few effective treatments for dementia or other forms of neurodegeneration, the authors pointed out, in part because these conditions are often only diagnosed once symptoms appear, whereas the underlying neurodegeneration may have “begun years, even decades, earlier.” This means that by the time patients take part in clinical trials, it may already be too late in the disease process to alter its course, they explained.

Timothy Rittman, BMBS, PhD, department of clinical neurosciences, University of Cambridge, and senior author, explained that the findings could also help identify people who can participate in clinical trials for potential new treatments. “The problem with clinical trials is that by necessity they often recruit patients with a diagnosis, but we know that by this point they are already some way down the road and their condition cannot be stopped. If we can find these individuals early enough, we’ll have a better chance of seeing if the drugs are effective,” he emphasized.

Commenting on the new research, Richard Oakley, PhD, associate director of research at Alzheimer’s Society, said: “Studies like this show the importance in continued investment in dementia research to revolutionize diagnosis and drive new treatments, so one day we will beat dementia.”

The research was funded by the Medical Research Council with support from the NIHR Cambridge Biomedical Research Centre. The authors reported no conflicts of interest.

A version of this article first appeared on Medscape UK.

U.K. scientists show it is possible to spot signs of brain impairment in patients as early as 9 years before they receive a diagnosis of dementia, offering hope for interventions to reduce the risk of the disease developing.

To date it has been unclear whether it might be possible to detect changes in brain function before the onset of symptoms, so researchers at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust set out to determine whether people who developed a range of neurodegenerative diagnoses demonstrated reduced cognitive function at their baseline assessment.

The authors explained: “The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, prediagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease.”
 

Prediagnostic cognitive and functional impairment identified

The researchers analyzed data from the UK Biobank and compared cognitive and functional measures, including problem solving, memory, reaction times and grip strength, as well as data on weight loss and gain and on the number of falls, in individuals who subsequently developed a number of dementia-related diseases (Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy), with those who did not have a neurodegenerative diagnosis. After adjustment for the effects of age, the same measures were regressed against time to diagnosis. The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The researchers found evidence of prediagnostic cognitive impairment and decline with time, particularly in Alzheimer’s disease where those who went on to develop the disease scored more poorly compared with healthy individuals when it came to problem solving tasks, reaction times, remembering lists of numbers, prospective memory, and pair matching. This was also the case for people who developed frontotemporal dementia, the authors said.

Nol Swaddiwudhipong, MB, of the University of Cambridge, and first author, said: “When we looked back at patients’ histories, it became clear that they were showing some cognitive impairment several years before their symptoms became obvious enough to prompt a diagnosis. The impairments were often subtle, but across a number of aspects of cognition.”

Prediagnostic functional impairment and decline was also observed in multiple diseases, the authors said. People who went on to develop Alzheimer’s disease were more likely than were healthy adults to have had a fall in the previous 12 months, with those patients who went on to develop progressive supranuclear palsy (PSP) being more than twice as likely as healthy individuals to have had a fall.

The time between baseline assessment and diagnosis varied between 4.7 years for dementia with Lewy bodies and 8.3 years for Alzheimer’s disease.

“For every condition studied – including Parkinson’s disease and dementia with Lewy bodies – patients reported poorer overall health at baseline,” said the authors.
 

Potential for new treatments

The study findings that cognitive and functional decline occurs “years before symptoms become obvious” in multiple neurodegenerative diseases, raises the possibility that in the future at-risk patients could be screened to help select those who would benefit from interventions to reduce their risk of developing one of the conditions, or to help identify patients suitable for recruitment to clinical trials for new treatments.

Dr Swaddiwudhipong emphasized: “This is a step towards us being able to screen people who are at greatest risk – for example, people over 50 or those who have high blood pressure or do not do enough exercise – and intervene at an earlier stage to help them reduce their risk.”

There are currently very few effective treatments for dementia or other forms of neurodegeneration, the authors pointed out, in part because these conditions are often only diagnosed once symptoms appear, whereas the underlying neurodegeneration may have “begun years, even decades, earlier.” This means that by the time patients take part in clinical trials, it may already be too late in the disease process to alter its course, they explained.

Timothy Rittman, BMBS, PhD, department of clinical neurosciences, University of Cambridge, and senior author, explained that the findings could also help identify people who can participate in clinical trials for potential new treatments. “The problem with clinical trials is that by necessity they often recruit patients with a diagnosis, but we know that by this point they are already some way down the road and their condition cannot be stopped. If we can find these individuals early enough, we’ll have a better chance of seeing if the drugs are effective,” he emphasized.

Commenting on the new research, Richard Oakley, PhD, associate director of research at Alzheimer’s Society, said: “Studies like this show the importance in continued investment in dementia research to revolutionize diagnosis and drive new treatments, so one day we will beat dementia.”

The research was funded by the Medical Research Council with support from the NIHR Cambridge Biomedical Research Centre. The authors reported no conflicts of interest.

A version of this article first appeared on Medscape UK.

The U.S. Food and Drug Administration has confirmed a nationwide shortage of the immediate release formulation of amphetamine mixed salts (Adderall, Adderall IR), which are approved for treating attention deficit hyperactivity disorder and narcolepsy.

The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.

The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.

Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.

“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.

Patients should work with their health care provider to determine their best treatment option, it added.

The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.

Its Drug Shortage webpage has additional information about the situation and is updated regularly.

“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.

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

The U.S. Food and Drug Administration has confirmed a nationwide shortage of the immediate release formulation of amphetamine mixed salts (Adderall, Adderall IR), which are approved for treating attention deficit hyperactivity disorder and narcolepsy.

The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.

The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.

Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.

“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.

Patients should work with their health care provider to determine their best treatment option, it added.

The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.

Its Drug Shortage webpage has additional information about the situation and is updated regularly.

“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.

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

The U.S. Food and Drug Administration has confirmed a nationwide shortage of the immediate release formulation of amphetamine mixed salts (Adderall, Adderall IR), which are approved for treating attention deficit hyperactivity disorder and narcolepsy.

The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.

The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.

Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.

“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.

Patients should work with their health care provider to determine their best treatment option, it added.

The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.

Its Drug Shortage webpage has additional information about the situation and is updated regularly.

“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.

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

Poor visual acuity, defined as difficulty discerning letters or numbers at a given distance, is associated with depression in middle-aged and older individuals, research suggests.

After multiple adjustments, analysis of data from more than 114,000 participants in the UK Biobank Study showed that visual impairment was linked to a 19% higher risk for depression.

In addition, imaging results showed a significant link between deteriorating brain structures and depression in those with poor visual acuity.

“Our findings highlight the value of visual health in association with mental health,” Xiayin Zhang, PhD, Guangdong Eye Institute, department of ophthalmology, Guangdong Provincial People’s Hospital, Guangzhou, China, and colleagues write.

“Screening of vision at an early stage should be embedded in the middle-aged and older population to stratify the vulnerable population at risk for depression,” the investigators add.

The findings were published online in JAMA Network Open.
 

UK biobank analyses

The analysis included 114,583 participants (54.5% women; mean age, 56.8 years) from the UK Biobank who completed standardized questionnaires and underwent ocular examinations.

To test distance visual acuity, all were asked to read letters on lines from the top to the bottom of a chart while wearing prescribed optical correction. Visual impairment was defined as visual acuity worse than 0.3 logarithm of the minimum angle of resolution (LogMAR) units.

Depressive symptoms were self-reported using the two-item Patient Health Questionnaire (PHQ-2), in which a score of 3 or more indicates depression. As well, a medical practitioner conducted an assessment of depression at baseline.

Among the participants, 87.2% had no visual impairment or depression and acted as the healthy control group. In addition, 3.2% showed visual impairment, 10% reported a diagnosis of depression, and 0.4% had both.

Researchers adjusted for age, sex, race, ethnicity, education, smoking, alcohol consumption, physical activity, family history of severe depression, obesity, hypertension, diabetes, hyperlipidemia, and deprivation on the Townsend index.

Among those with visual impairment, 12.4% had depression, compared with 9.9% without visual impairment.
 

Structure deterioration

After adjusting for potential confounders, visual impairment was associated with a 19% higher risk for depression (odds ratio, 1.19; 95% confidence interval, 1.05-1.34; P = .003). In addition, 1-line–worse visual acuity was associated with 5% higher odds of depression (OR, 1.05; 95% CI, 1.04-1.07; P < .001).

The association between visual acuity and depression was found in both younger (39-58 years) and older (59-72 years) groups, as well as in both men and women.

The researchers also explored the association between depressive symptoms and brain structure using MRI scans from a subset of 7,844 individuals (51% women; 2% with visual impairment).

Results showed linear associations between PHQ-2 scores and the left volume of gray matter in the supracalcarine cortex (coefficient, 7.61; 95% CI, 3.9-11.3; adjusted P = .006).

The investigators note that the supracalcarine cortex is spatially connected to the primary visual cortex, suggesting the visual cortex may be involved in the pathogenesis of depression.

PHQ-2 scores were also associated with mean isotropic volume fraction (ISOVF) in the right fornix (cres) and/or stria terminalis (coefficient, .003; 95% CI, 0.001-0.004; adjusted P = .01).

The links “could be moderated by visual acuity, whereby increased PHQ score was associated with higher ISOVF levels only among those with poorer visual acuity (P = .02 for interaction),” the investigators report.

These results “suggest that poorer visual acuity was associated with greater depressive symptoms and may have contributed to the related deterioration of the fornix and stria terminalis,” they add.

They note that previous studies have supported the hypothesis that the fornix and stria terminalis are involved in the pathophysiology of other brain-related conditions, including schizophrenia, bipolar disorder, and autism spectrum disorder.

However, the investigators did not have information on how long the participants had experienced visual impairment, so they couldn’t investigate whether results were affected by time. Additional study limitations cited were that depression may affect vision and that a large proportion of the participants (89.3%) were White.
 

Study ‘adds nuance’

Commenting on the study, Ipsit V. Vahia, MD, of the department of psychiatry at Harvard Medical School, Boston, and associate chief of geriatric psychiatry at McLean Hospital, Belmont, Mass., said the study “adds nuance to our understanding” of the well-established relationship between vision deficits and depression.

“It indicates that even mild visual deficits may be associated with depression,” said Dr. Vahia, who was not involved with the research.

The investigators validated this association by showing that visual acuity was also associated with neuroimaging markers of depression, he added.

Although the study was not designed to demonstrate causal relationships between mood and vision and its findings do not confirm that correcting visual acuity deficits will resolve depressive symptoms, “the large study sample and high quality of data should give clinicians confidence in the study’s findings,” Dr. Vahia said.

“Correcting visual acuity deficits can be considered standard care for older adults worldwide, and this study suggests that providing this standard care could also benefit mental health,” he concluded.

The study was supported by the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, the Outstanding Young Talent Trainee Program of Guangdong Provincial People’s Hospital, the Guangdong Provincial People’s Hospital Scientific Research Funds for Leading Medical Talents and Distinguished Young Scholars in Guangdong Province, the Talent Introduction Fund of Guangdong Provincial People’s Hospital, the Science and Technology Program of Guangzhou, China, the Project of Special Research on Cardiovascular Diseases, the Research Foundation of Medical Science and Technology of Guangdong Province, the University of Melbourne at Research Accelerator Program, and the CERA (Centre for Eye Research Australia) Foundation and Victorian State Government for the Centre for Eye Research Australia. The investigators and Dr. Vahia have reported no relevant financial relationships.

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

Poor visual acuity, defined as difficulty discerning letters or numbers at a given distance, is associated with depression in middle-aged and older individuals, research suggests.

After multiple adjustments, analysis of data from more than 114,000 participants in the UK Biobank Study showed that visual impairment was linked to a 19% higher risk for depression.

In addition, imaging results showed a significant link between deteriorating brain structures and depression in those with poor visual acuity.

“Our findings highlight the value of visual health in association with mental health,” Xiayin Zhang, PhD, Guangdong Eye Institute, department of ophthalmology, Guangdong Provincial People’s Hospital, Guangzhou, China, and colleagues write.

“Screening of vision at an early stage should be embedded in the middle-aged and older population to stratify the vulnerable population at risk for depression,” the investigators add.

The findings were published online in JAMA Network Open.
 

UK biobank analyses

The analysis included 114,583 participants (54.5% women; mean age, 56.8 years) from the UK Biobank who completed standardized questionnaires and underwent ocular examinations.

To test distance visual acuity, all were asked to read letters on lines from the top to the bottom of a chart while wearing prescribed optical correction. Visual impairment was defined as visual acuity worse than 0.3 logarithm of the minimum angle of resolution (LogMAR) units.

Depressive symptoms were self-reported using the two-item Patient Health Questionnaire (PHQ-2), in which a score of 3 or more indicates depression. As well, a medical practitioner conducted an assessment of depression at baseline.

Among the participants, 87.2% had no visual impairment or depression and acted as the healthy control group. In addition, 3.2% showed visual impairment, 10% reported a diagnosis of depression, and 0.4% had both.

Researchers adjusted for age, sex, race, ethnicity, education, smoking, alcohol consumption, physical activity, family history of severe depression, obesity, hypertension, diabetes, hyperlipidemia, and deprivation on the Townsend index.

Among those with visual impairment, 12.4% had depression, compared with 9.9% without visual impairment.
 

Structure deterioration

After adjusting for potential confounders, visual impairment was associated with a 19% higher risk for depression (odds ratio, 1.19; 95% confidence interval, 1.05-1.34; P = .003). In addition, 1-line–worse visual acuity was associated with 5% higher odds of depression (OR, 1.05; 95% CI, 1.04-1.07; P < .001).

The association between visual acuity and depression was found in both younger (39-58 years) and older (59-72 years) groups, as well as in both men and women.

The researchers also explored the association between depressive symptoms and brain structure using MRI scans from a subset of 7,844 individuals (51% women; 2% with visual impairment).

Results showed linear associations between PHQ-2 scores and the left volume of gray matter in the supracalcarine cortex (coefficient, 7.61; 95% CI, 3.9-11.3; adjusted P = .006).

The investigators note that the supracalcarine cortex is spatially connected to the primary visual cortex, suggesting the visual cortex may be involved in the pathogenesis of depression.

PHQ-2 scores were also associated with mean isotropic volume fraction (ISOVF) in the right fornix (cres) and/or stria terminalis (coefficient, .003; 95% CI, 0.001-0.004; adjusted P = .01).

The links “could be moderated by visual acuity, whereby increased PHQ score was associated with higher ISOVF levels only among those with poorer visual acuity (P = .02 for interaction),” the investigators report.

These results “suggest that poorer visual acuity was associated with greater depressive symptoms and may have contributed to the related deterioration of the fornix and stria terminalis,” they add.

They note that previous studies have supported the hypothesis that the fornix and stria terminalis are involved in the pathophysiology of other brain-related conditions, including schizophrenia, bipolar disorder, and autism spectrum disorder.

However, the investigators did not have information on how long the participants had experienced visual impairment, so they couldn’t investigate whether results were affected by time. Additional study limitations cited were that depression may affect vision and that a large proportion of the participants (89.3%) were White.
 

Study ‘adds nuance’

Commenting on the study, Ipsit V. Vahia, MD, of the department of psychiatry at Harvard Medical School, Boston, and associate chief of geriatric psychiatry at McLean Hospital, Belmont, Mass., said the study “adds nuance to our understanding” of the well-established relationship between vision deficits and depression.

“It indicates that even mild visual deficits may be associated with depression,” said Dr. Vahia, who was not involved with the research.

The investigators validated this association by showing that visual acuity was also associated with neuroimaging markers of depression, he added.

Although the study was not designed to demonstrate causal relationships between mood and vision and its findings do not confirm that correcting visual acuity deficits will resolve depressive symptoms, “the large study sample and high quality of data should give clinicians confidence in the study’s findings,” Dr. Vahia said.

“Correcting visual acuity deficits can be considered standard care for older adults worldwide, and this study suggests that providing this standard care could also benefit mental health,” he concluded.

The study was supported by the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, the Outstanding Young Talent Trainee Program of Guangdong Provincial People’s Hospital, the Guangdong Provincial People’s Hospital Scientific Research Funds for Leading Medical Talents and Distinguished Young Scholars in Guangdong Province, the Talent Introduction Fund of Guangdong Provincial People’s Hospital, the Science and Technology Program of Guangzhou, China, the Project of Special Research on Cardiovascular Diseases, the Research Foundation of Medical Science and Technology of Guangdong Province, the University of Melbourne at Research Accelerator Program, and the CERA (Centre for Eye Research Australia) Foundation and Victorian State Government for the Centre for Eye Research Australia. The investigators and Dr. Vahia have reported no relevant financial relationships.

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

Poor visual acuity, defined as difficulty discerning letters or numbers at a given distance, is associated with depression in middle-aged and older individuals, research suggests.

After multiple adjustments, analysis of data from more than 114,000 participants in the UK Biobank Study showed that visual impairment was linked to a 19% higher risk for depression.

In addition, imaging results showed a significant link between deteriorating brain structures and depression in those with poor visual acuity.

“Our findings highlight the value of visual health in association with mental health,” Xiayin Zhang, PhD, Guangdong Eye Institute, department of ophthalmology, Guangdong Provincial People’s Hospital, Guangzhou, China, and colleagues write.

“Screening of vision at an early stage should be embedded in the middle-aged and older population to stratify the vulnerable population at risk for depression,” the investigators add.

The findings were published online in JAMA Network Open.
 

UK biobank analyses

The analysis included 114,583 participants (54.5% women; mean age, 56.8 years) from the UK Biobank who completed standardized questionnaires and underwent ocular examinations.

To test distance visual acuity, all were asked to read letters on lines from the top to the bottom of a chart while wearing prescribed optical correction. Visual impairment was defined as visual acuity worse than 0.3 logarithm of the minimum angle of resolution (LogMAR) units.

Depressive symptoms were self-reported using the two-item Patient Health Questionnaire (PHQ-2), in which a score of 3 or more indicates depression. As well, a medical practitioner conducted an assessment of depression at baseline.

Among the participants, 87.2% had no visual impairment or depression and acted as the healthy control group. In addition, 3.2% showed visual impairment, 10% reported a diagnosis of depression, and 0.4% had both.

Researchers adjusted for age, sex, race, ethnicity, education, smoking, alcohol consumption, physical activity, family history of severe depression, obesity, hypertension, diabetes, hyperlipidemia, and deprivation on the Townsend index.

Among those with visual impairment, 12.4% had depression, compared with 9.9% without visual impairment.
 

Structure deterioration

After adjusting for potential confounders, visual impairment was associated with a 19% higher risk for depression (odds ratio, 1.19; 95% confidence interval, 1.05-1.34; P = .003). In addition, 1-line–worse visual acuity was associated with 5% higher odds of depression (OR, 1.05; 95% CI, 1.04-1.07; P < .001).

The association between visual acuity and depression was found in both younger (39-58 years) and older (59-72 years) groups, as well as in both men and women.

The researchers also explored the association between depressive symptoms and brain structure using MRI scans from a subset of 7,844 individuals (51% women; 2% with visual impairment).

Results showed linear associations between PHQ-2 scores and the left volume of gray matter in the supracalcarine cortex (coefficient, 7.61; 95% CI, 3.9-11.3; adjusted P = .006).

The investigators note that the supracalcarine cortex is spatially connected to the primary visual cortex, suggesting the visual cortex may be involved in the pathogenesis of depression.

PHQ-2 scores were also associated with mean isotropic volume fraction (ISOVF) in the right fornix (cres) and/or stria terminalis (coefficient, .003; 95% CI, 0.001-0.004; adjusted P = .01).

The links “could be moderated by visual acuity, whereby increased PHQ score was associated with higher ISOVF levels only among those with poorer visual acuity (P = .02 for interaction),” the investigators report.

These results “suggest that poorer visual acuity was associated with greater depressive symptoms and may have contributed to the related deterioration of the fornix and stria terminalis,” they add.

They note that previous studies have supported the hypothesis that the fornix and stria terminalis are involved in the pathophysiology of other brain-related conditions, including schizophrenia, bipolar disorder, and autism spectrum disorder.

However, the investigators did not have information on how long the participants had experienced visual impairment, so they couldn’t investigate whether results were affected by time. Additional study limitations cited were that depression may affect vision and that a large proportion of the participants (89.3%) were White.
 

Study ‘adds nuance’

Commenting on the study, Ipsit V. Vahia, MD, of the department of psychiatry at Harvard Medical School, Boston, and associate chief of geriatric psychiatry at McLean Hospital, Belmont, Mass., said the study “adds nuance to our understanding” of the well-established relationship between vision deficits and depression.

“It indicates that even mild visual deficits may be associated with depression,” said Dr. Vahia, who was not involved with the research.

The investigators validated this association by showing that visual acuity was also associated with neuroimaging markers of depression, he added.

Although the study was not designed to demonstrate causal relationships between mood and vision and its findings do not confirm that correcting visual acuity deficits will resolve depressive symptoms, “the large study sample and high quality of data should give clinicians confidence in the study’s findings,” Dr. Vahia said.

“Correcting visual acuity deficits can be considered standard care for older adults worldwide, and this study suggests that providing this standard care could also benefit mental health,” he concluded.

The study was supported by the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, the Outstanding Young Talent Trainee Program of Guangdong Provincial People’s Hospital, the Guangdong Provincial People’s Hospital Scientific Research Funds for Leading Medical Talents and Distinguished Young Scholars in Guangdong Province, the Talent Introduction Fund of Guangdong Provincial People’s Hospital, the Science and Technology Program of Guangzhou, China, the Project of Special Research on Cardiovascular Diseases, the Research Foundation of Medical Science and Technology of Guangdong Province, the University of Melbourne at Research Accelerator Program, and the CERA (Centre for Eye Research Australia) Foundation and Victorian State Government for the Centre for Eye Research Australia. The investigators and Dr. Vahia have reported no relevant financial relationships.

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

Patients with perinatal depression who used a specialized online tool showed improvement in symptoms, compared with controls who received routine care, based on data from 191 individuals.

Although perinatal depression affects approximately 17% of pregnant women and 13% of postpartum women, the condition is often underrecognized and undertreated, Brian Danaher, PhD, of Influents Innovations, Eugene, Ore., and colleagues wrote. Meta-analyses have shown that e-health interventions based on cognitive-behavioral therapy (CBT) can improve depression in general and perinatal depression in particular.

An e-health program known as the MomMoodBooster has demonstrated effectiveness at reducing postpartum depression, and the researchers evaluated the effectiveness of a perinatal version.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers randomized 95 pregnant women and 96 postpartum women who met screening criteria for depression to routine care for perinatal depression, which included a 24/7 crisis hotline and a referral network or PDP plus a version of the MomMoodBooster with a perinatal depression component (MMB2). Participants were aged 18 and older, with no active suicidal ideation. The average age was 32 years; 84% were non-Hispanic, 67% were White, and 94% were married or in a long-term relationship. During the 12 weeks, each of six sessions became accessible online in sequence.

The primary endpoint was the change in outcomes at 12 weeks after the start of the program, with depressive symptom severity measured using the Patient Health Questionnaire (PHQ-9). Anxiety was assessed as a secondary outcome by using the Depression Anxiety Stress Scale. The minimal clinically important difference (MCID) was used to evaluate clinical significance, and was defined as a reduction in PHQ-9 of at least 5 points from baseline.

After controlling for perinatal status at baseline and assessment time, the MMB2 group had significantly greater decreases in depression severity and stress compared with the routine care group. In addition, based on MCID, significantly more women in the MMB2 group showed improvements in depression, compared with the routine care group (43% vs. 26%; odds ratio, 2.12; P = .015).

A total of 88 of the 89 women in the MMB2 group accessed the sessions, and approximately half (49%) viewed all six sessions.

Of the women who used the MMB2 program, 96% said that it was easy to use, 93% said they would recommend it, and 83% said it was helpful to them.

The study findings were limited by several factors including the lack of long-term follow-up data and inability to determine the durability of the treatment effects, the researchers noted. Another key limitation is the demographics of the study population (slightly older and a greater proportion of White individuals than the national average), which may not be representative of all perinatal women in the United States.

However, the results are consistent with findings from previous studies, including meta-analyses of CBT-based programs, the researchers wrote.

“When used in a largely self-directed approach, MMB2 could fill the gap when in-person treatment options are limited as well as for women whose circumstances (COVID) and/or concerns (stigma, costs) reduce the acceptability of in-person help,” they said. Use of e-health programs such as MMB2 could increase the scope of treatment for perinatal depression.
 

Expanding e-health options may improve outcomes and reduce disparities

Perinatal and postpartum depression is one of the most common conditions affecting pregnancy, Lisette D. Tanner, MD, of Emory University, Atlanta, said in an interview. “Depression can have serious consequences for both maternal and neonatal well-being, including preterm birth, low birth weight, and poor bonding, as well as delayed emotional and cognitive development of the newborn.

“While clinicians are encouraged to screen patients during and after pregnancy for signs and symptoms of depression, once identified, the availability of effective treatment is limited. Access to mental health resources is a long-standing disparity in medicine, and therefore research investigating readily available e-health treatment strategies is critically important,” said Dr. Tanner, who was not involved in the study.

In the current study, “I was surprised by the number of patients who saw a clinically significant improvement in depression scores in such a short period of time. An average of only 20 days elapsed between baseline and post-test scores and almost 43% of patients showed improvement. Mental health interventions typically take longer to demonstrate an effect, both medication and talk therapies,” she said.  

“The largest barrier to adoption of any e-health modality into clinical practice is often the cost of implementation and maintaining infrastructure,” said Dr. Tanner. “A cost-effectiveness analysis of this intervention would be helpful to better delineate the value of such of program in comparison to more traditional treatments.”

More research is needed on the effectiveness of the intervention for specific populations, such as groups with lower socioeconomic status and patients with chronic mood disorders, Dr. Tanner said. “Additionally, introducing the program in locations with limited access to mental health resources would support more widespread implementation.”

The study was supported by the National Institutes of Mental Health. The researchers had no financial conflicts to disclose. Dr. Tanner had no financial conflicts to disclose.

Patients with perinatal depression who used a specialized online tool showed improvement in symptoms, compared with controls who received routine care, based on data from 191 individuals.

Although perinatal depression affects approximately 17% of pregnant women and 13% of postpartum women, the condition is often underrecognized and undertreated, Brian Danaher, PhD, of Influents Innovations, Eugene, Ore., and colleagues wrote. Meta-analyses have shown that e-health interventions based on cognitive-behavioral therapy (CBT) can improve depression in general and perinatal depression in particular.

An e-health program known as the MomMoodBooster has demonstrated effectiveness at reducing postpartum depression, and the researchers evaluated the effectiveness of a perinatal version.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers randomized 95 pregnant women and 96 postpartum women who met screening criteria for depression to routine care for perinatal depression, which included a 24/7 crisis hotline and a referral network or PDP plus a version of the MomMoodBooster with a perinatal depression component (MMB2). Participants were aged 18 and older, with no active suicidal ideation. The average age was 32 years; 84% were non-Hispanic, 67% were White, and 94% were married or in a long-term relationship. During the 12 weeks, each of six sessions became accessible online in sequence.

The primary endpoint was the change in outcomes at 12 weeks after the start of the program, with depressive symptom severity measured using the Patient Health Questionnaire (PHQ-9). Anxiety was assessed as a secondary outcome by using the Depression Anxiety Stress Scale. The minimal clinically important difference (MCID) was used to evaluate clinical significance, and was defined as a reduction in PHQ-9 of at least 5 points from baseline.

After controlling for perinatal status at baseline and assessment time, the MMB2 group had significantly greater decreases in depression severity and stress compared with the routine care group. In addition, based on MCID, significantly more women in the MMB2 group showed improvements in depression, compared with the routine care group (43% vs. 26%; odds ratio, 2.12; P = .015).

A total of 88 of the 89 women in the MMB2 group accessed the sessions, and approximately half (49%) viewed all six sessions.

Of the women who used the MMB2 program, 96% said that it was easy to use, 93% said they would recommend it, and 83% said it was helpful to them.

The study findings were limited by several factors including the lack of long-term follow-up data and inability to determine the durability of the treatment effects, the researchers noted. Another key limitation is the demographics of the study population (slightly older and a greater proportion of White individuals than the national average), which may not be representative of all perinatal women in the United States.

However, the results are consistent with findings from previous studies, including meta-analyses of CBT-based programs, the researchers wrote.

“When used in a largely self-directed approach, MMB2 could fill the gap when in-person treatment options are limited as well as for women whose circumstances (COVID) and/or concerns (stigma, costs) reduce the acceptability of in-person help,” they said. Use of e-health programs such as MMB2 could increase the scope of treatment for perinatal depression.
 

Expanding e-health options may improve outcomes and reduce disparities

Perinatal and postpartum depression is one of the most common conditions affecting pregnancy, Lisette D. Tanner, MD, of Emory University, Atlanta, said in an interview. “Depression can have serious consequences for both maternal and neonatal well-being, including preterm birth, low birth weight, and poor bonding, as well as delayed emotional and cognitive development of the newborn.

“While clinicians are encouraged to screen patients during and after pregnancy for signs and symptoms of depression, once identified, the availability of effective treatment is limited. Access to mental health resources is a long-standing disparity in medicine, and therefore research investigating readily available e-health treatment strategies is critically important,” said Dr. Tanner, who was not involved in the study.

In the current study, “I was surprised by the number of patients who saw a clinically significant improvement in depression scores in such a short period of time. An average of only 20 days elapsed between baseline and post-test scores and almost 43% of patients showed improvement. Mental health interventions typically take longer to demonstrate an effect, both medication and talk therapies,” she said.  

“The largest barrier to adoption of any e-health modality into clinical practice is often the cost of implementation and maintaining infrastructure,” said Dr. Tanner. “A cost-effectiveness analysis of this intervention would be helpful to better delineate the value of such of program in comparison to more traditional treatments.”

More research is needed on the effectiveness of the intervention for specific populations, such as groups with lower socioeconomic status and patients with chronic mood disorders, Dr. Tanner said. “Additionally, introducing the program in locations with limited access to mental health resources would support more widespread implementation.”

The study was supported by the National Institutes of Mental Health. The researchers had no financial conflicts to disclose. Dr. Tanner had no financial conflicts to disclose.

Patients with perinatal depression who used a specialized online tool showed improvement in symptoms, compared with controls who received routine care, based on data from 191 individuals.

Although perinatal depression affects approximately 17% of pregnant women and 13% of postpartum women, the condition is often underrecognized and undertreated, Brian Danaher, PhD, of Influents Innovations, Eugene, Ore., and colleagues wrote. Meta-analyses have shown that e-health interventions based on cognitive-behavioral therapy (CBT) can improve depression in general and perinatal depression in particular.

An e-health program known as the MomMoodBooster has demonstrated effectiveness at reducing postpartum depression, and the researchers evaluated the effectiveness of a perinatal version.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers randomized 95 pregnant women and 96 postpartum women who met screening criteria for depression to routine care for perinatal depression, which included a 24/7 crisis hotline and a referral network or PDP plus a version of the MomMoodBooster with a perinatal depression component (MMB2). Participants were aged 18 and older, with no active suicidal ideation. The average age was 32 years; 84% were non-Hispanic, 67% were White, and 94% were married or in a long-term relationship. During the 12 weeks, each of six sessions became accessible online in sequence.

The primary endpoint was the change in outcomes at 12 weeks after the start of the program, with depressive symptom severity measured using the Patient Health Questionnaire (PHQ-9). Anxiety was assessed as a secondary outcome by using the Depression Anxiety Stress Scale. The minimal clinically important difference (MCID) was used to evaluate clinical significance, and was defined as a reduction in PHQ-9 of at least 5 points from baseline.

After controlling for perinatal status at baseline and assessment time, the MMB2 group had significantly greater decreases in depression severity and stress compared with the routine care group. In addition, based on MCID, significantly more women in the MMB2 group showed improvements in depression, compared with the routine care group (43% vs. 26%; odds ratio, 2.12; P = .015).

A total of 88 of the 89 women in the MMB2 group accessed the sessions, and approximately half (49%) viewed all six sessions.

Of the women who used the MMB2 program, 96% said that it was easy to use, 93% said they would recommend it, and 83% said it was helpful to them.

The study findings were limited by several factors including the lack of long-term follow-up data and inability to determine the durability of the treatment effects, the researchers noted. Another key limitation is the demographics of the study population (slightly older and a greater proportion of White individuals than the national average), which may not be representative of all perinatal women in the United States.

However, the results are consistent with findings from previous studies, including meta-analyses of CBT-based programs, the researchers wrote.

“When used in a largely self-directed approach, MMB2 could fill the gap when in-person treatment options are limited as well as for women whose circumstances (COVID) and/or concerns (stigma, costs) reduce the acceptability of in-person help,” they said. Use of e-health programs such as MMB2 could increase the scope of treatment for perinatal depression.
 

Expanding e-health options may improve outcomes and reduce disparities

Perinatal and postpartum depression is one of the most common conditions affecting pregnancy, Lisette D. Tanner, MD, of Emory University, Atlanta, said in an interview. “Depression can have serious consequences for both maternal and neonatal well-being, including preterm birth, low birth weight, and poor bonding, as well as delayed emotional and cognitive development of the newborn.

“While clinicians are encouraged to screen patients during and after pregnancy for signs and symptoms of depression, once identified, the availability of effective treatment is limited. Access to mental health resources is a long-standing disparity in medicine, and therefore research investigating readily available e-health treatment strategies is critically important,” said Dr. Tanner, who was not involved in the study.

In the current study, “I was surprised by the number of patients who saw a clinically significant improvement in depression scores in such a short period of time. An average of only 20 days elapsed between baseline and post-test scores and almost 43% of patients showed improvement. Mental health interventions typically take longer to demonstrate an effect, both medication and talk therapies,” she said.  

“The largest barrier to adoption of any e-health modality into clinical practice is often the cost of implementation and maintaining infrastructure,” said Dr. Tanner. “A cost-effectiveness analysis of this intervention would be helpful to better delineate the value of such of program in comparison to more traditional treatments.”

More research is needed on the effectiveness of the intervention for specific populations, such as groups with lower socioeconomic status and patients with chronic mood disorders, Dr. Tanner said. “Additionally, introducing the program in locations with limited access to mental health resources would support more widespread implementation.”

The study was supported by the National Institutes of Mental Health. The researchers had no financial conflicts to disclose. Dr. Tanner had no financial conflicts to disclose.

Suicide notes left by elderly people provide a unique opportunity to better understand and prevent suicide in this often vulnerable population.

A new analysis of notes penned by seniors who died by suicide reveals several common themes. These include feeling as if they were a burden, feelings of guilt, experiencing mental illness, loneliness, or isolation, as well as poor health and/or disability.

“The most important message [in our findings] is that there is hope,” study investigator Ari B. Cuperfain, MD, Temerty Faculty of Medicine, University of Toronto, told this news organization.

“Suicide risk is modifiable, and we encourage that care providers sensitively explore thoughts of suicide in patients expressing depressive thoughts or difficulty coping with other life stressors,” he said.

The study was published online in The American Journal of Geriatric Psychiatry.
 

Opportunity for intervention

Most previous studies of late-life suicide have focused on risk factors rather than the themes and meaning underlying individuals’ distress.

Dr. Cuperfain’s group had previously analyzed suicide notes to “explore the relationship between suicide and an individual’s experience with mental health care in all age groups,” he said. For the current study, the investigators analyzed the subset of notes written exclusively by older adults.

The researchers “hypothesized that suicide notes could provide a unique window into the thought processes of older adults during a critical window for mental health intervention,” he added.

Although effective screening for suicidality in older adults can mitigate suicide risk, the frequency of suicide screening decreases with increasing age, the authors noted.

In addition, suicide attempts are typically more often fatal in older adults than in the general population. Understanding the motivations for suicide in this vulnerable population can inform potential interventions.

The researchers used a constructivist grounded theory framework to analyze suicide notes available from their previous study and notes obtained from the Office of the Coroner in Toronto from adults aged 65 years and older (n = 29; mean [SD], age 76.2 [8.3] years; 79% men).

The investigators began with open coding of the notes, “specifying a short name to a segment of data that summarizes and accounts for each piece of data.” They then used a series of techniques to identify terms and themes (repeated patterns of ideas reflected in the data).

Once themes had been determined, they identified “pathways between these themes and the final act of suicide.”
 

Common themes

Four major themes emerged in the analysis of the suicide notes.

Recurring terms included “pain,” “[poor] sleep,” or “[wakeful] nights,” as well as “sorry” (either about past actions or about the suicide), and “I just can’t” (referring to the inability to carry on).

The suicide notes “provided the older writers’ conceptual schema for suicide, elucidating the cognitive process linking their narratives to the acts of suicide.” Examples included the following:

• Suicide as a way out or solution to an insoluble problem.
• Suicide as the final act in a long road of suffering.
• Suicide as the logical culmination of life (the person “lived a good life”).

“Our study enriches the understanding of ‘why’ rather than just ‘which’ older adults die by suicide,” the authors noted.

“Care providers can help older adults at risk of suicide through a combination of treatment options. These include physician involvement to manage depression, psychosis, or pain, psychotherapy to reframe certain ways of thinking, or social activities to reduce isolation,” Dr. Cuperfain said.

“By understanding the experiences of older adults and what is underlying their suicidal thoughts, these interventions can be tailored specifically for the individual experiencing distress,” he added.
 

Untangling suicide drivers

Commenting on the study, Yeates Conwell, MD, professor and vice chair, department of psychiatry, University of Rochester (N.Y.) Medical Center, said that “by analyzing the suicide notes of older people who died by suicide, the paper lends a unique perspective to our understanding of why they may have taken their lives.”

University of Rochester Medical Center

Dr. Conwell, director of the geriatric psychiatry program and codirector of the Center for the Study and Prevention of Suicide, University of Rochester, and author of an accompanying editorial, said that “by including the decedent’s own voice, the analysis of notes is a useful complement to other approaches used for the study of suicide in this age group”.

However, “like all other approaches, it is subject to potential biases in interpretation. The meaning in the notes must be derived with careful consideration of context, both what is said and what is not said, and the likelihood that both overt and covert messages are contained in and between their lines,” cautioned Dr. Conwell.

“Acknowledging the strength and limitations of each approach to the study of suicide death, together they can help untangle its drivers and support the search for effective, acceptable, and scalable prevention interventions. No one approach alone, however, will reveal the ‘cause’ of suicide,” Dr. Conwell wrote.

No source of study funding was provided. Dr. Cuperfain reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Conwell reports no relevant financial relationships.

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

Suicide notes left by elderly people provide a unique opportunity to better understand and prevent suicide in this often vulnerable population.

A new analysis of notes penned by seniors who died by suicide reveals several common themes. These include feeling as if they were a burden, feelings of guilt, experiencing mental illness, loneliness, or isolation, as well as poor health and/or disability.

“The most important message [in our findings] is that there is hope,” study investigator Ari B. Cuperfain, MD, Temerty Faculty of Medicine, University of Toronto, told this news organization.

“Suicide risk is modifiable, and we encourage that care providers sensitively explore thoughts of suicide in patients expressing depressive thoughts or difficulty coping with other life stressors,” he said.

The study was published online in The American Journal of Geriatric Psychiatry.
 

Opportunity for intervention

Most previous studies of late-life suicide have focused on risk factors rather than the themes and meaning underlying individuals’ distress.

Dr. Cuperfain’s group had previously analyzed suicide notes to “explore the relationship between suicide and an individual’s experience with mental health care in all age groups,” he said. For the current study, the investigators analyzed the subset of notes written exclusively by older adults.

The researchers “hypothesized that suicide notes could provide a unique window into the thought processes of older adults during a critical window for mental health intervention,” he added.

Although effective screening for suicidality in older adults can mitigate suicide risk, the frequency of suicide screening decreases with increasing age, the authors noted.

In addition, suicide attempts are typically more often fatal in older adults than in the general population. Understanding the motivations for suicide in this vulnerable population can inform potential interventions.

The researchers used a constructivist grounded theory framework to analyze suicide notes available from their previous study and notes obtained from the Office of the Coroner in Toronto from adults aged 65 years and older (n = 29; mean [SD], age 76.2 [8.3] years; 79% men).

The investigators began with open coding of the notes, “specifying a short name to a segment of data that summarizes and accounts for each piece of data.” They then used a series of techniques to identify terms and themes (repeated patterns of ideas reflected in the data).

Once themes had been determined, they identified “pathways between these themes and the final act of suicide.”
 

Common themes

Four major themes emerged in the analysis of the suicide notes.

Recurring terms included “pain,” “[poor] sleep,” or “[wakeful] nights,” as well as “sorry” (either about past actions or about the suicide), and “I just can’t” (referring to the inability to carry on).

The suicide notes “provided the older writers’ conceptual schema for suicide, elucidating the cognitive process linking their narratives to the acts of suicide.” Examples included the following:

• Suicide as a way out or solution to an insoluble problem.
• Suicide as the final act in a long road of suffering.
• Suicide as the logical culmination of life (the person “lived a good life”).

“Our study enriches the understanding of ‘why’ rather than just ‘which’ older adults die by suicide,” the authors noted.

“Care providers can help older adults at risk of suicide through a combination of treatment options. These include physician involvement to manage depression, psychosis, or pain, psychotherapy to reframe certain ways of thinking, or social activities to reduce isolation,” Dr. Cuperfain said.

“By understanding the experiences of older adults and what is underlying their suicidal thoughts, these interventions can be tailored specifically for the individual experiencing distress,” he added.
 

Untangling suicide drivers

Commenting on the study, Yeates Conwell, MD, professor and vice chair, department of psychiatry, University of Rochester (N.Y.) Medical Center, said that “by analyzing the suicide notes of older people who died by suicide, the paper lends a unique perspective to our understanding of why they may have taken their lives.”

University of Rochester Medical Center

Dr. Conwell, director of the geriatric psychiatry program and codirector of the Center for the Study and Prevention of Suicide, University of Rochester, and author of an accompanying editorial, said that “by including the decedent’s own voice, the analysis of notes is a useful complement to other approaches used for the study of suicide in this age group”.

However, “like all other approaches, it is subject to potential biases in interpretation. The meaning in the notes must be derived with careful consideration of context, both what is said and what is not said, and the likelihood that both overt and covert messages are contained in and between their lines,” cautioned Dr. Conwell.

“Acknowledging the strength and limitations of each approach to the study of suicide death, together they can help untangle its drivers and support the search for effective, acceptable, and scalable prevention interventions. No one approach alone, however, will reveal the ‘cause’ of suicide,” Dr. Conwell wrote.

No source of study funding was provided. Dr. Cuperfain reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Conwell reports no relevant financial relationships.

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

Suicide notes left by elderly people provide a unique opportunity to better understand and prevent suicide in this often vulnerable population.

A new analysis of notes penned by seniors who died by suicide reveals several common themes. These include feeling as if they were a burden, feelings of guilt, experiencing mental illness, loneliness, or isolation, as well as poor health and/or disability.

“The most important message [in our findings] is that there is hope,” study investigator Ari B. Cuperfain, MD, Temerty Faculty of Medicine, University of Toronto, told this news organization.

“Suicide risk is modifiable, and we encourage that care providers sensitively explore thoughts of suicide in patients expressing depressive thoughts or difficulty coping with other life stressors,” he said.

The study was published online in The American Journal of Geriatric Psychiatry.
 

Opportunity for intervention

Most previous studies of late-life suicide have focused on risk factors rather than the themes and meaning underlying individuals’ distress.

Dr. Cuperfain’s group had previously analyzed suicide notes to “explore the relationship between suicide and an individual’s experience with mental health care in all age groups,” he said. For the current study, the investigators analyzed the subset of notes written exclusively by older adults.

The researchers “hypothesized that suicide notes could provide a unique window into the thought processes of older adults during a critical window for mental health intervention,” he added.

Although effective screening for suicidality in older adults can mitigate suicide risk, the frequency of suicide screening decreases with increasing age, the authors noted.

In addition, suicide attempts are typically more often fatal in older adults than in the general population. Understanding the motivations for suicide in this vulnerable population can inform potential interventions.

The researchers used a constructivist grounded theory framework to analyze suicide notes available from their previous study and notes obtained from the Office of the Coroner in Toronto from adults aged 65 years and older (n = 29; mean [SD], age 76.2 [8.3] years; 79% men).

The investigators began with open coding of the notes, “specifying a short name to a segment of data that summarizes and accounts for each piece of data.” They then used a series of techniques to identify terms and themes (repeated patterns of ideas reflected in the data).

Once themes had been determined, they identified “pathways between these themes and the final act of suicide.”
 

Common themes

Four major themes emerged in the analysis of the suicide notes.

Recurring terms included “pain,” “[poor] sleep,” or “[wakeful] nights,” as well as “sorry” (either about past actions or about the suicide), and “I just can’t” (referring to the inability to carry on).

The suicide notes “provided the older writers’ conceptual schema for suicide, elucidating the cognitive process linking their narratives to the acts of suicide.” Examples included the following:

• Suicide as a way out or solution to an insoluble problem.
• Suicide as the final act in a long road of suffering.
• Suicide as the logical culmination of life (the person “lived a good life”).

“Our study enriches the understanding of ‘why’ rather than just ‘which’ older adults die by suicide,” the authors noted.

“Care providers can help older adults at risk of suicide through a combination of treatment options. These include physician involvement to manage depression, psychosis, or pain, psychotherapy to reframe certain ways of thinking, or social activities to reduce isolation,” Dr. Cuperfain said.

“By understanding the experiences of older adults and what is underlying their suicidal thoughts, these interventions can be tailored specifically for the individual experiencing distress,” he added.
 

Untangling suicide drivers

Commenting on the study, Yeates Conwell, MD, professor and vice chair, department of psychiatry, University of Rochester (N.Y.) Medical Center, said that “by analyzing the suicide notes of older people who died by suicide, the paper lends a unique perspective to our understanding of why they may have taken their lives.”

University of Rochester Medical Center

Dr. Conwell, director of the geriatric psychiatry program and codirector of the Center for the Study and Prevention of Suicide, University of Rochester, and author of an accompanying editorial, said that “by including the decedent’s own voice, the analysis of notes is a useful complement to other approaches used for the study of suicide in this age group”.

However, “like all other approaches, it is subject to potential biases in interpretation. The meaning in the notes must be derived with careful consideration of context, both what is said and what is not said, and the likelihood that both overt and covert messages are contained in and between their lines,” cautioned Dr. Conwell.

“Acknowledging the strength and limitations of each approach to the study of suicide death, together they can help untangle its drivers and support the search for effective, acceptable, and scalable prevention interventions. No one approach alone, however, will reveal the ‘cause’ of suicide,” Dr. Conwell wrote.

No source of study funding was provided. Dr. Cuperfain reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Conwell reports no relevant financial relationships.

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

According to the United States Transgender Survey, 39% of respondents reported experiencing serious psychological distress (based on the Kessler 6 Psychological Distress Scale) in the past 30 days compared with 5% in the general population.¹ Additionally, 40% of respondents attempted suicide in their lifetime, compared with 5% in the general population.¹ Almost half of respondents reported being sexually assaulted at some time in their life, and 10% reported being sexually assaulted in the past year.¹

Studies have also shown that veterans and active-duty service members experience worse mental health outcomes and are at increased risk for suicide than civilians and nonveterans.^2-5 About 1 in 4 active-duty service members meet the criteria for diagnosis of a mental illness.⁴ Service members were found to have higher rates of probable anxiety and posttraumatic stress disorder (PTSD) compared with the general population.^2,6 In 2018, veteran suicide deaths accounted for about 13% of all deaths by suicide in the US even though veterans only accounted for about 7% of the adult population in that year.^5,7 Also in 2018, about 17 veterans committed suicide per day.⁵ According to the Health Related Behaviors Survey of active-duty service members, about 18% reported thinking about attempting suicide some time in their lives compared with 4% of the general population.^2,3 Additionally, 5% of service members reported previous suicide attempts compared with 0.5% in the general population.^2,3 It is clear that transgender individuals, veterans, and service members have certain mental health outcomes that are worse than that of the general population.^1-7

Transgender individuals along with LGB (lesbian, gay, bisexual) individuals have long faced discrimination and unfair treatment in the military.^8-11 In the 1920s, the first written policies were established that banned gay men from serving in the military.⁹ The US Department of Defense (DoD) continued these policies until in 1993, the “Don’t Ask Don’t Tell” policy was established, which had the façade of being more inclusive for LGB individuals but forced LGB service members to hide their sexual identity and continued the anti-LGBTQ messages that previous policies had created.^8,10,11 In 2010, “Don’t Ask Don’t Tell” was repealed, which allowed LGB individuals to serve in the military without concealing their sexual orientation and without fear of discharge based on their sexual identity.¹¹ This repeal did not allow transgender individuals to serve their country as the DoD categorized transgender identity as a medical and mental health disorder.^8,11

In 2016, the ban on transgender individuals serving in the military was lifted, and service members could no longer be discharged or turned away from joining the military based on gender identity.^8,12 However, in 2018, this order was reversed. The new policy stated that new service members must meet requirements and standards of their sex assigned at birth, and individuals with a history of gender dysphoria or those who have received gender-affirming medical or surgical treatment were prohibited to serve in the military.^8,13 This policy did not apply to service members who joined before it took effect. Finally, in April 2021, the current policy took effect, permitting transgender individuals to openly serve in the military. The current policy states that service members cannot be discharged or denied reenlistment based on their gender identity and provides support to receive gender-affirming medical care.¹⁴ Although transgender individuals are now accepted in military service, there is still much progress needed to promote equity among transgender service members.

Methods

We conducted a systematic review of articles presenting data on mental health outcomes in transgender veterans and active-duty service members. The National Library of Medicine PubMed database was searched using the following search terms in various combinations: mental health outcomes, transgender, veterans, military, active duty, substance use, and sexual trauma. The literature search was performed in August 2021 and included articles published through July 31, 2021. Methodology, size, demographics, measures, and main findings were extracted from each article. All studies were eligible for inclusion regardless of sample size. Studies that examined the LGBTQ population without separating transgender individuals were excluded. Studies that examined mental health outcomes including, but not limited to, PTSD, depression, suicidality, anxiety, and substance use disorders (SUDs) in addition to sexual trauma were included. Studies that only examined physical health outcomes were excluded. Qualitative studies, case reports, and papers that did not present original data were excluded (Figure).

Results

Our search resulted in 86 publications. After excluding 65 articles that did not meet the inclusion criteria, 19 studies were included in this review. The Appendix shows the summary of findings from each study, including the study size and results. All studies were conducted in the United States. Most papers used a cross-sectional study design. Most of the studies focused on transgender veterans, but some included data on transgender active-duty service members.

We separated the findings into the following categories based on the variables measured: mental health, including depression, anxiety, PTSD, and serious mental illness; suicidality and self-harm; substance use; and military sexual trauma (MST). Many studies overlapped multiple categories.

Mental Health

Most of the studies included reported that transgender veterans have statistically significant worse mental health outcomes compared with cisgender veterans.^28-30 In addition, transgender active-duty service members were found to have worse mental health outcomes than cisgender active-duty service members.³¹ MST and discrimination were associated with worse mental health outcomes among transgender veterans.^32,33 One study showed a different result than others and found that transgender older adults with prior military service had higher psychological health-related quality of life and lower depressive symptoms than those without prior military service (P = .02 and .04, respectively).³⁴ Another study compared transgender veterans with active-duty service members and found that transgender veterans reported higher rates of depression (64.6% vs 30.9%; χ² = 11.68; P = .001) and anxiety (41.3% vs 18.2%; χ² = 6.54; P = .01) compared with transgender service members.³⁵

Suicidality and Self-harm

Eleven of the 19 studies included measured suicidality and/or self-harm as an outcome. Transgender veterans and active-duty service members were found to have higher odds of suicidality than their cisgender counterparts.^16,28,29,31 In addition, transgender veterans may die by suicide at a younger age than cisgender veterans.³⁶ Stigma and gender-related discrimination were found to be associated with suicidal ideation.^33,37-39 Transgender veterans were less likely than transgender nonveterans to report nonsuicidal self-injury (NSSI).⁴⁰

Substance Use

Two studies focused on substance use, while 5 other studies included substance use in their measures. One of these 2 studies that focused only on substance use outcomes found that transgender veterans were more likely than cisgender veterans to have any SUD (7.2% vs 3.9%; P < .001), in addition to specifically cannabis (3.4% vs 1.5%; P < .001), amphetamine (1.1% vs 0.3%; P < .001), and cocaine use disorders (1.5% vs 1.1%; P < .001).⁴¹

Another study reported that transgender veterans had lower odds of self-reported alcohol use but had greater odds of having alcohol-related diagnoses compared with cisgender veterans.⁴² Of the other studies, it was found that a higher percentage of transgender veterans were diagnosed with an SUD compared with transgender active-duty service members, and transgender veterans were more likely than cisgender veterans to be diagnosed with alcohol use disorder.^29,31 Additionally, rural transgender veterans had increased odds of tobacco use disorder compared with transgender veterans who lived in urban areas.⁴³

Military Sexual Trauma

Five of the studies included examined MST, defined as sexual assault or sexual harassment that is experienced during military service.⁴⁴ Studies found that 15% to 17% of transgender veterans experienced MST.^32,45 Transgender veterans were more likely to report MST than cisgender veterans.^28,29 MST was found to be consistently associated with depression and PTSD.^32,45 A high percentage (83.9%) of transgender active-duty service members reported experiencing sexual harassment and almost one-third experienced sexual assault.⁴⁶

Discussion

Outcomes examined in this review included MST, substance use, suicidality, and symptoms of depression, anxiety, and PTSD among transgender active-duty service members and veterans. To our knowledge, no other review on this topic exists. There is a review of the health and well-being of LGBTQ veterans and service members, but a majority of the included studies did not separate transgender individuals from LGB persons.¹⁷ This review of transgender individuals showed similar results to the review of LGBTQ individuals.¹⁷ This review also presented similar results to previous studies that indicated that transgender individuals in the general population have worse mental health outcomes compared with their cisgender counterparts, in addition to studies that showed that veterans and active-duty service members have worse mental health outcomes compared with civilians and nonveterans.^1-5 The population of focus in this review faced a unique set of challenges, being that they belonged to both of these subsets of the population, both of which experienced worse mental health outcomes, according to the literature.

Studies included in our review found that transgender veterans and service members have worse mental health outcomes than cisgender veterans and service members.^28-31 This outcome was predicted based on previous data collection among transgender individuals, veterans, and active-duty service members. One of the studies included found different results and concluded that prior military service was a protective factor against poorer mental health outcomes.³⁴ This could be, in part, due to veterans’ access to care through the US Department of Veterans Affairs (VA) system. It has been found that transgender veterans use VA services at higher rates than the general population of veterans and that barriers to care were found more for medical treatment than for mental health treatment.⁴⁷ One study found that almost 70% of transgender veterans who used VA services were satisfied with their mental health care.⁴⁸ In contrast, another study included in our review found that transgender veterans had worse mental health outcomes than transgender service members, possibly showing that even with access to care, the burden of stigma and discrimination worsens mental health over time.³¹ Although it has been shown that transgender veterans may feel comfortable disclosing their gender identity to their health care professional, many barriers to care have been identified, such as insensitivity and lack of knowledge about transgender care among clinicians.^49-51 With this information, it would be useful to ensure proper training for health care professionals on providing gender-affirming care.

Most of the studies also found that transgender veterans and service members had greater odds of suicidal thoughts and events than cisgender veterans and service members.^16,28,29,35 On the contrary, transgender veterans were less likely than transgender nonveterans to report NSSI, which could be for various reasons.⁴⁰ Transgender veterans may report less NSSI but experience it at similar rates, or veteran status may be a protective factor for NSSI.

Limitations

This review was limited due to the lack of data collected from transgender veterans and service members. The studies included did not allow for standardized comparisons and did not use identical measures. Some papers compared transgender veterans with transgender nonveterans, some transgender veterans and/or service members with cisgender veterans and/or service members, and some transgender veterans with transgender service members. There were some consistent results found across the studies, but some studies showed contradictory results or no significant differences within a certain category. It is difficult to compare such different study designs and various participant populations. Additional research is required to verify and replicate these results.

Conclusions

Although this review was limited due to the lack of consistent study designs in the literature examining the mental health of transgender veterans and active-duty service members, overall results showed that transgender veterans and service members experience worse mental health outcomes than their cisgender counterparts. With this knowledge and exploring the history of discrimination that this population has faced, improved systems must be put into place to better serve this population and improve health outcomes. Additional research is required to examine the effects of gender-affirming care on mental health among transgender veterans and service members.

According to the United States Transgender Survey, 39% of respondents reported experiencing serious psychological distress (based on the Kessler 6 Psychological Distress Scale) in the past 30 days compared with 5% in the general population.¹ Additionally, 40% of respondents attempted suicide in their lifetime, compared with 5% in the general population.¹ Almost half of respondents reported being sexually assaulted at some time in their life, and 10% reported being sexually assaulted in the past year.¹

Studies have also shown that veterans and active-duty service members experience worse mental health outcomes and are at increased risk for suicide than civilians and nonveterans.^2-5 About 1 in 4 active-duty service members meet the criteria for diagnosis of a mental illness.⁴ Service members were found to have higher rates of probable anxiety and posttraumatic stress disorder (PTSD) compared with the general population.^2,6 In 2018, veteran suicide deaths accounted for about 13% of all deaths by suicide in the US even though veterans only accounted for about 7% of the adult population in that year.^5,7 Also in 2018, about 17 veterans committed suicide per day.⁵ According to the Health Related Behaviors Survey of active-duty service members, about 18% reported thinking about attempting suicide some time in their lives compared with 4% of the general population.^2,3 Additionally, 5% of service members reported previous suicide attempts compared with 0.5% in the general population.^2,3 It is clear that transgender individuals, veterans, and service members have certain mental health outcomes that are worse than that of the general population.^1-7

Transgender individuals along with LGB (lesbian, gay, bisexual) individuals have long faced discrimination and unfair treatment in the military.^8-11 In the 1920s, the first written policies were established that banned gay men from serving in the military.⁹ The US Department of Defense (DoD) continued these policies until in 1993, the “Don’t Ask Don’t Tell” policy was established, which had the façade of being more inclusive for LGB individuals but forced LGB service members to hide their sexual identity and continued the anti-LGBTQ messages that previous policies had created.^8,10,11 In 2010, “Don’t Ask Don’t Tell” was repealed, which allowed LGB individuals to serve in the military without concealing their sexual orientation and without fear of discharge based on their sexual identity.¹¹ This repeal did not allow transgender individuals to serve their country as the DoD categorized transgender identity as a medical and mental health disorder.^8,11

In 2016, the ban on transgender individuals serving in the military was lifted, and service members could no longer be discharged or turned away from joining the military based on gender identity.^8,12 However, in 2018, this order was reversed. The new policy stated that new service members must meet requirements and standards of their sex assigned at birth, and individuals with a history of gender dysphoria or those who have received gender-affirming medical or surgical treatment were prohibited to serve in the military.^8,13 This policy did not apply to service members who joined before it took effect. Finally, in April 2021, the current policy took effect, permitting transgender individuals to openly serve in the military. The current policy states that service members cannot be discharged or denied reenlistment based on their gender identity and provides support to receive gender-affirming medical care.¹⁴ Although transgender individuals are now accepted in military service, there is still much progress needed to promote equity among transgender service members.

Methods

We conducted a systematic review of articles presenting data on mental health outcomes in transgender veterans and active-duty service members. The National Library of Medicine PubMed database was searched using the following search terms in various combinations: mental health outcomes, transgender, veterans, military, active duty, substance use, and sexual trauma. The literature search was performed in August 2021 and included articles published through July 31, 2021. Methodology, size, demographics, measures, and main findings were extracted from each article. All studies were eligible for inclusion regardless of sample size. Studies that examined the LGBTQ population without separating transgender individuals were excluded. Studies that examined mental health outcomes including, but not limited to, PTSD, depression, suicidality, anxiety, and substance use disorders (SUDs) in addition to sexual trauma were included. Studies that only examined physical health outcomes were excluded. Qualitative studies, case reports, and papers that did not present original data were excluded (Figure).

Results

Our search resulted in 86 publications. After excluding 65 articles that did not meet the inclusion criteria, 19 studies were included in this review. The Appendix shows the summary of findings from each study, including the study size and results. All studies were conducted in the United States. Most papers used a cross-sectional study design. Most of the studies focused on transgender veterans, but some included data on transgender active-duty service members.

We separated the findings into the following categories based on the variables measured: mental health, including depression, anxiety, PTSD, and serious mental illness; suicidality and self-harm; substance use; and military sexual trauma (MST). Many studies overlapped multiple categories.

Mental Health

Most of the studies included reported that transgender veterans have statistically significant worse mental health outcomes compared with cisgender veterans.^28-30 In addition, transgender active-duty service members were found to have worse mental health outcomes than cisgender active-duty service members.³¹ MST and discrimination were associated with worse mental health outcomes among transgender veterans.^32,33 One study showed a different result than others and found that transgender older adults with prior military service had higher psychological health-related quality of life and lower depressive symptoms than those without prior military service (P = .02 and .04, respectively).³⁴ Another study compared transgender veterans with active-duty service members and found that transgender veterans reported higher rates of depression (64.6% vs 30.9%; χ² = 11.68; P = .001) and anxiety (41.3% vs 18.2%; χ² = 6.54; P = .01) compared with transgender service members.³⁵

Suicidality and Self-harm

Eleven of the 19 studies included measured suicidality and/or self-harm as an outcome. Transgender veterans and active-duty service members were found to have higher odds of suicidality than their cisgender counterparts.^16,28,29,31 In addition, transgender veterans may die by suicide at a younger age than cisgender veterans.³⁶ Stigma and gender-related discrimination were found to be associated with suicidal ideation.^33,37-39 Transgender veterans were less likely than transgender nonveterans to report nonsuicidal self-injury (NSSI).⁴⁰

Substance Use

Two studies focused on substance use, while 5 other studies included substance use in their measures. One of these 2 studies that focused only on substance use outcomes found that transgender veterans were more likely than cisgender veterans to have any SUD (7.2% vs 3.9%; P < .001), in addition to specifically cannabis (3.4% vs 1.5%; P < .001), amphetamine (1.1% vs 0.3%; P < .001), and cocaine use disorders (1.5% vs 1.1%; P < .001).⁴¹

Another study reported that transgender veterans had lower odds of self-reported alcohol use but had greater odds of having alcohol-related diagnoses compared with cisgender veterans.⁴² Of the other studies, it was found that a higher percentage of transgender veterans were diagnosed with an SUD compared with transgender active-duty service members, and transgender veterans were more likely than cisgender veterans to be diagnosed with alcohol use disorder.^29,31 Additionally, rural transgender veterans had increased odds of tobacco use disorder compared with transgender veterans who lived in urban areas.⁴³

Military Sexual Trauma

Five of the studies included examined MST, defined as sexual assault or sexual harassment that is experienced during military service.⁴⁴ Studies found that 15% to 17% of transgender veterans experienced MST.^32,45 Transgender veterans were more likely to report MST than cisgender veterans.^28,29 MST was found to be consistently associated with depression and PTSD.^32,45 A high percentage (83.9%) of transgender active-duty service members reported experiencing sexual harassment and almost one-third experienced sexual assault.⁴⁶

Discussion

Outcomes examined in this review included MST, substance use, suicidality, and symptoms of depression, anxiety, and PTSD among transgender active-duty service members and veterans. To our knowledge, no other review on this topic exists. There is a review of the health and well-being of LGBTQ veterans and service members, but a majority of the included studies did not separate transgender individuals from LGB persons.¹⁷ This review of transgender individuals showed similar results to the review of LGBTQ individuals.¹⁷ This review also presented similar results to previous studies that indicated that transgender individuals in the general population have worse mental health outcomes compared with their cisgender counterparts, in addition to studies that showed that veterans and active-duty service members have worse mental health outcomes compared with civilians and nonveterans.^1-5 The population of focus in this review faced a unique set of challenges, being that they belonged to both of these subsets of the population, both of which experienced worse mental health outcomes, according to the literature.

Studies included in our review found that transgender veterans and service members have worse mental health outcomes than cisgender veterans and service members.^28-31 This outcome was predicted based on previous data collection among transgender individuals, veterans, and active-duty service members. One of the studies included found different results and concluded that prior military service was a protective factor against poorer mental health outcomes.³⁴ This could be, in part, due to veterans’ access to care through the US Department of Veterans Affairs (VA) system. It has been found that transgender veterans use VA services at higher rates than the general population of veterans and that barriers to care were found more for medical treatment than for mental health treatment.⁴⁷ One study found that almost 70% of transgender veterans who used VA services were satisfied with their mental health care.⁴⁸ In contrast, another study included in our review found that transgender veterans had worse mental health outcomes than transgender service members, possibly showing that even with access to care, the burden of stigma and discrimination worsens mental health over time.³¹ Although it has been shown that transgender veterans may feel comfortable disclosing their gender identity to their health care professional, many barriers to care have been identified, such as insensitivity and lack of knowledge about transgender care among clinicians.^49-51 With this information, it would be useful to ensure proper training for health care professionals on providing gender-affirming care.

Most of the studies also found that transgender veterans and service members had greater odds of suicidal thoughts and events than cisgender veterans and service members.^16,28,29,35 On the contrary, transgender veterans were less likely than transgender nonveterans to report NSSI, which could be for various reasons.⁴⁰ Transgender veterans may report less NSSI but experience it at similar rates, or veteran status may be a protective factor for NSSI.

Limitations

This review was limited due to the lack of data collected from transgender veterans and service members. The studies included did not allow for standardized comparisons and did not use identical measures. Some papers compared transgender veterans with transgender nonveterans, some transgender veterans and/or service members with cisgender veterans and/or service members, and some transgender veterans with transgender service members. There were some consistent results found across the studies, but some studies showed contradictory results or no significant differences within a certain category. It is difficult to compare such different study designs and various participant populations. Additional research is required to verify and replicate these results.

Conclusions

Although this review was limited due to the lack of consistent study designs in the literature examining the mental health of transgender veterans and active-duty service members, overall results showed that transgender veterans and service members experience worse mental health outcomes than their cisgender counterparts. With this knowledge and exploring the history of discrimination that this population has faced, improved systems must be put into place to better serve this population and improve health outcomes. Additional research is required to examine the effects of gender-affirming care on mental health among transgender veterans and service members.

According to the United States Transgender Survey, 39% of respondents reported experiencing serious psychological distress (based on the Kessler 6 Psychological Distress Scale) in the past 30 days compared with 5% in the general population.¹ Additionally, 40% of respondents attempted suicide in their lifetime, compared with 5% in the general population.¹ Almost half of respondents reported being sexually assaulted at some time in their life, and 10% reported being sexually assaulted in the past year.¹

Studies have also shown that veterans and active-duty service members experience worse mental health outcomes and are at increased risk for suicide than civilians and nonveterans.^2-5 About 1 in 4 active-duty service members meet the criteria for diagnosis of a mental illness.⁴ Service members were found to have higher rates of probable anxiety and posttraumatic stress disorder (PTSD) compared with the general population.^2,6 In 2018, veteran suicide deaths accounted for about 13% of all deaths by suicide in the US even though veterans only accounted for about 7% of the adult population in that year.^5,7 Also in 2018, about 17 veterans committed suicide per day.⁵ According to the Health Related Behaviors Survey of active-duty service members, about 18% reported thinking about attempting suicide some time in their lives compared with 4% of the general population.^2,3 Additionally, 5% of service members reported previous suicide attempts compared with 0.5% in the general population.^2,3 It is clear that transgender individuals, veterans, and service members have certain mental health outcomes that are worse than that of the general population.^1-7

Transgender individuals along with LGB (lesbian, gay, bisexual) individuals have long faced discrimination and unfair treatment in the military.^8-11 In the 1920s, the first written policies were established that banned gay men from serving in the military.⁹ The US Department of Defense (DoD) continued these policies until in 1993, the “Don’t Ask Don’t Tell” policy was established, which had the façade of being more inclusive for LGB individuals but forced LGB service members to hide their sexual identity and continued the anti-LGBTQ messages that previous policies had created.^8,10,11 In 2010, “Don’t Ask Don’t Tell” was repealed, which allowed LGB individuals to serve in the military without concealing their sexual orientation and without fear of discharge based on their sexual identity.¹¹ This repeal did not allow transgender individuals to serve their country as the DoD categorized transgender identity as a medical and mental health disorder.^8,11

In 2016, the ban on transgender individuals serving in the military was lifted, and service members could no longer be discharged or turned away from joining the military based on gender identity.^8,12 However, in 2018, this order was reversed. The new policy stated that new service members must meet requirements and standards of their sex assigned at birth, and individuals with a history of gender dysphoria or those who have received gender-affirming medical or surgical treatment were prohibited to serve in the military.^8,13 This policy did not apply to service members who joined before it took effect. Finally, in April 2021, the current policy took effect, permitting transgender individuals to openly serve in the military. The current policy states that service members cannot be discharged or denied reenlistment based on their gender identity and provides support to receive gender-affirming medical care.¹⁴ Although transgender individuals are now accepted in military service, there is still much progress needed to promote equity among transgender service members.

Methods

We conducted a systematic review of articles presenting data on mental health outcomes in transgender veterans and active-duty service members. The National Library of Medicine PubMed database was searched using the following search terms in various combinations: mental health outcomes, transgender, veterans, military, active duty, substance use, and sexual trauma. The literature search was performed in August 2021 and included articles published through July 31, 2021. Methodology, size, demographics, measures, and main findings were extracted from each article. All studies were eligible for inclusion regardless of sample size. Studies that examined the LGBTQ population without separating transgender individuals were excluded. Studies that examined mental health outcomes including, but not limited to, PTSD, depression, suicidality, anxiety, and substance use disorders (SUDs) in addition to sexual trauma were included. Studies that only examined physical health outcomes were excluded. Qualitative studies, case reports, and papers that did not present original data were excluded (Figure).

Results

Our search resulted in 86 publications. After excluding 65 articles that did not meet the inclusion criteria, 19 studies were included in this review. The Appendix shows the summary of findings from each study, including the study size and results. All studies were conducted in the United States. Most papers used a cross-sectional study design. Most of the studies focused on transgender veterans, but some included data on transgender active-duty service members.

We separated the findings into the following categories based on the variables measured: mental health, including depression, anxiety, PTSD, and serious mental illness; suicidality and self-harm; substance use; and military sexual trauma (MST). Many studies overlapped multiple categories.

Mental Health

Most of the studies included reported that transgender veterans have statistically significant worse mental health outcomes compared with cisgender veterans.^28-30 In addition, transgender active-duty service members were found to have worse mental health outcomes than cisgender active-duty service members.³¹ MST and discrimination were associated with worse mental health outcomes among transgender veterans.^32,33 One study showed a different result than others and found that transgender older adults with prior military service had higher psychological health-related quality of life and lower depressive symptoms than those without prior military service (P = .02 and .04, respectively).³⁴ Another study compared transgender veterans with active-duty service members and found that transgender veterans reported higher rates of depression (64.6% vs 30.9%; χ² = 11.68; P = .001) and anxiety (41.3% vs 18.2%; χ² = 6.54; P = .01) compared with transgender service members.³⁵

Suicidality and Self-harm

Eleven of the 19 studies included measured suicidality and/or self-harm as an outcome. Transgender veterans and active-duty service members were found to have higher odds of suicidality than their cisgender counterparts.^16,28,29,31 In addition, transgender veterans may die by suicide at a younger age than cisgender veterans.³⁶ Stigma and gender-related discrimination were found to be associated with suicidal ideation.^33,37-39 Transgender veterans were less likely than transgender nonveterans to report nonsuicidal self-injury (NSSI).⁴⁰

Substance Use

Two studies focused on substance use, while 5 other studies included substance use in their measures. One of these 2 studies that focused only on substance use outcomes found that transgender veterans were more likely than cisgender veterans to have any SUD (7.2% vs 3.9%; P < .001), in addition to specifically cannabis (3.4% vs 1.5%; P < .001), amphetamine (1.1% vs 0.3%; P < .001), and cocaine use disorders (1.5% vs 1.1%; P < .001).⁴¹

Another study reported that transgender veterans had lower odds of self-reported alcohol use but had greater odds of having alcohol-related diagnoses compared with cisgender veterans.⁴² Of the other studies, it was found that a higher percentage of transgender veterans were diagnosed with an SUD compared with transgender active-duty service members, and transgender veterans were more likely than cisgender veterans to be diagnosed with alcohol use disorder.^29,31 Additionally, rural transgender veterans had increased odds of tobacco use disorder compared with transgender veterans who lived in urban areas.⁴³

Military Sexual Trauma

Five of the studies included examined MST, defined as sexual assault or sexual harassment that is experienced during military service.⁴⁴ Studies found that 15% to 17% of transgender veterans experienced MST.^32,45 Transgender veterans were more likely to report MST than cisgender veterans.^28,29 MST was found to be consistently associated with depression and PTSD.^32,45 A high percentage (83.9%) of transgender active-duty service members reported experiencing sexual harassment and almost one-third experienced sexual assault.⁴⁶

Discussion

Outcomes examined in this review included MST, substance use, suicidality, and symptoms of depression, anxiety, and PTSD among transgender active-duty service members and veterans. To our knowledge, no other review on this topic exists. There is a review of the health and well-being of LGBTQ veterans and service members, but a majority of the included studies did not separate transgender individuals from LGB persons.¹⁷ This review of transgender individuals showed similar results to the review of LGBTQ individuals.¹⁷ This review also presented similar results to previous studies that indicated that transgender individuals in the general population have worse mental health outcomes compared with their cisgender counterparts, in addition to studies that showed that veterans and active-duty service members have worse mental health outcomes compared with civilians and nonveterans.^1-5 The population of focus in this review faced a unique set of challenges, being that they belonged to both of these subsets of the population, both of which experienced worse mental health outcomes, according to the literature.

Studies included in our review found that transgender veterans and service members have worse mental health outcomes than cisgender veterans and service members.^28-31 This outcome was predicted based on previous data collection among transgender individuals, veterans, and active-duty service members. One of the studies included found different results and concluded that prior military service was a protective factor against poorer mental health outcomes.³⁴ This could be, in part, due to veterans’ access to care through the US Department of Veterans Affairs (VA) system. It has been found that transgender veterans use VA services at higher rates than the general population of veterans and that barriers to care were found more for medical treatment than for mental health treatment.⁴⁷ One study found that almost 70% of transgender veterans who used VA services were satisfied with their mental health care.⁴⁸ In contrast, another study included in our review found that transgender veterans had worse mental health outcomes than transgender service members, possibly showing that even with access to care, the burden of stigma and discrimination worsens mental health over time.³¹ Although it has been shown that transgender veterans may feel comfortable disclosing their gender identity to their health care professional, many barriers to care have been identified, such as insensitivity and lack of knowledge about transgender care among clinicians.^49-51 With this information, it would be useful to ensure proper training for health care professionals on providing gender-affirming care.

Most of the studies also found that transgender veterans and service members had greater odds of suicidal thoughts and events than cisgender veterans and service members.^16,28,29,35 On the contrary, transgender veterans were less likely than transgender nonveterans to report NSSI, which could be for various reasons.⁴⁰ Transgender veterans may report less NSSI but experience it at similar rates, or veteran status may be a protective factor for NSSI.

Limitations

This review was limited due to the lack of data collected from transgender veterans and service members. The studies included did not allow for standardized comparisons and did not use identical measures. Some papers compared transgender veterans with transgender nonveterans, some transgender veterans and/or service members with cisgender veterans and/or service members, and some transgender veterans with transgender service members. There were some consistent results found across the studies, but some studies showed contradictory results or no significant differences within a certain category. It is difficult to compare such different study designs and various participant populations. Additional research is required to verify and replicate these results.

Conclusions

Although this review was limited due to the lack of consistent study designs in the literature examining the mental health of transgender veterans and active-duty service members, overall results showed that transgender veterans and service members experience worse mental health outcomes than their cisgender counterparts. With this knowledge and exploring the history of discrimination that this population has faced, improved systems must be put into place to better serve this population and improve health outcomes. Additional research is required to examine the effects of gender-affirming care on mental health among transgender veterans and service members.

ANAHEIM, CALIF. – A modular digital intervention to teach mental health skills to youth awaiting transfer to psychiatric care appeared feasible to implement and acceptable to teens and their parents, according to a study presented at the American Academy of Pediatrics National Conference.

“This program has the potential to teach evidence-based mental health skills to youth during boarding, providing a head start on recovery prior to psychiatric hospitalization,” study coauthor Samantha House, DO, MPH, section chief of pediatric hospital medicine at Dartmouth Hitchcock Medical Center, Lebanon, N.H., told attendees.

Mental health boarding has become increasingly common as psychiatric care resources have been stretched by a crisis in pediatric mental health that began even before the COVID pandemic. Since youth often don’t receive evidence-based therapies while boarding, Dr. House and her coauthor, JoAnna K. Leyenaar, MD, PhD, MPH, developed a pilot program called I-CARE, which stands for Improving Care, Accelerating Recovery and Education.

I-CARE is a digital health intervention that combines videos on a tablet with workbook exercises that teach mental health skills. The seven modules include an introduction and one each on schedule-making, safety planning, psychoeducation, behavioral activation, relaxation skills, and mindfulness skills. Licensed nursing assistants who have received a 6-hour training from a clinical psychologist administer the program and provide safety supervision during boarding.

“I-CARE was designed to be largely self-directed, supported by ‘coaches’ who are not mental health professionals,” Dr. Leyenaar, vice chair of research in the department of pediatrics and an associate professor of pediatrics at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. With this model, the program requires minimal additional resources beyond the tablets and workbooks, and is designed for implementation in settings with few or no mental health professionals, she said.

Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington, Seattle, and an attending physician at Seattle Children’s Hospital, was not involved in the study but was excited to see it.

“I think it’s a really good idea, and I like that it’s being studied,” Dr. Breuner said in an interview. She said the health care and public health system has let down an entire population who data had shown were experiencing mental health problems.

“We knew before the pandemic that behavioral health issues were creeping up slowly with anxiety, depression, suicidal ideation, and, of course, substance use disorders and eating disorders, and not a lot was being done about it,” Dr. Breuner said, and the pandemic exacerbated those issues. ”I don’t know why no one realized that this was going to be the downstream effect of having no socialization for kids for 18 months and limited resources for those who we need desperately to provide care for,” especially BIPOC [Black, Indigenous, and people of color] kids and underresourced kids.

That sentiment is exactly what inspired the creation of the program, according to Dr. Leyenaar.

The I-CARE program was implemented at Dartmouth Hitchcock Medical Center in November 2021 for adolescents aged 12-17 who were boarding because of suicidality or self-harm. The program and study excluded youth with psychosis and other cognitive or behavioral conditions that didn’t fit with the skills taught by the module training.

The researchers qualitatively evaluated the I-CARE program in youth who were offered at least two I-CARE modules and with parents present during boarding.

Twenty-four youth, with a median age of 14, were offered the I-CARE program between November 2021 and April 2022 while boarding for a median 8 days. Most of the patients were female (79%), and a third were transgender or gender diverse. Most were White (83%), and about two-thirds had Medicaid (62.5%). The most common diagnoses among the participants were major depressive disorder (71%) and generalized anxiety disorder (46%). Others included PTSD (29%), restrictive eating disorder (21%), and bipolar disorder (12.5%).

All offered the program completed the first module, and 79% participated in additional modules. The main reason for discontinuation was transfer to another facility, but a few youth either refused to engage with the program or felt they knew the material well enough that they weren’t benefiting from it.

The evaluation involved 16 youth, seven parents, and 17 clinicians. On a Likert scale, the composite score for the program’s appropriateness – suitability, applicability, and meeting needs – was an average 3.7, with a higher rating from clinicians (4.3) and caregivers (3.5) than youth (2.8).

“Some youth felt the intervention was better suited for a younger audience or those with less familiarity with mental health skills, but they acknowledged that the intervention would be helpful and appropriate for others,” Dr. House, who is also an assistant professor of pediatrics at Geisel School of Medicine, said.

Youth rated the acceptability of the program more highly (3.6) and all three groups found it easy to use, with an average feasibility score of 4 across the board. The program’s acceptability received an average score of 4 from parents and clinicians.

”Teens seem to particularly value the psychoeducation module that explains the relationship between thoughts and feelings, as well as the opportunity to develop a personalized safety plan,” Dr. Leyenaar said.

Among the challenges expressed by the participating teens were that the loud sounds and beeping in the hospital made it difficult to practice mindfulness and that they often had to wait for staff to be available to do I-CARE.

“I feel like not many people have been trained yet,” one teen said, “so to have more nurses available to do I-CARE would be helpful.”

Another participant found the coaches helpful. “Sometimes they were my nurse, sometimes they were someone I never met before. … and also, they were all really, really nice,” the teen said.

Another teen regarded the material as “really surface-level mental health stuff” that they thought “could be helpful to other people who are here for the first time.” But others found the content more beneficial.

“The videos were helpful. … I was worried that they weren’t going to be very informative, but they did make sense to me,” one participant said. “They weren’t overcomplicating things. … They weren’t saying anything I didn’t understand, so that was good.”

The researchers next plan to conduct a multisite study to determine the program’s effectiveness in improving health outcomes and reducing suicidal ideation. Dr. House and Dr. Leyenaar are looking at ways to refine the program.

”We may narrow the age range for participants, with an upper age limit of 16, since some older teens said that the modules were best suited for a younger audience,” Dr. Leyenaar said. “We are also discussing how to best support youth who are readmitted to our hospital and have participated in I-CARE previously.”

Dr. Breuner said she would be interested to see, in future studies of the program, whether it reduced the likelihood of inpatient psychiatric stay, the length of psychiatric stay after admission, or the risk of readmission. She also wondered if the program might be offered in languages other than English, whether a version might be specifically designed for BIPOC youth, and whether the researchers had considered offering the intervention to caregivers as well.

The modules are teaching the kids but should they also be teaching the parents? Dr. Breuner wondered. A lot of times, she said, the parents are bringing these kids in because they don’t know what to do and can’t deal with them anymore. Offering modules on the same skills to caregivers would also enable the caregivers to reinforce and reteach the skills to their children, especially if the youth struggled to really take in what the modules were trying to teach.

Dr. Leyenaar said she expects buy-in for a program like this would be high at other institutions, but it’s premature to scale it up until they’ve conducted at least another clinical trial on its effectiveness. The biggest potential barrier to buy-in that Dr. Breuner perceived would be cost.

“It’s always difficult when it costs money” since the hospital needs to train the clinicians who provide the care, Dr. Breuner said, but it’s possible those costs could be offset if the program reduces the risk of readmission or return to the emergency department.

While the overall risk of harms from the intervention are low, Dr. Breuner said it is important to be conscious that the intervention may not necessarily be appropriate for all youth.

“There’s always risk when there’s a trauma background, and you have to be very careful, especially with mindfulness training,” Dr. Breuner said. For those with a history of abuse or other adverse childhood experiences “for someone to get into a very calm, still place can actually be counterproductive.”

Dr. Breuner especially appreciated that the researchers involved the youth and caregivers in the evaluation process. “That the parents expressed positive attitudes is really incredible,” she said.

Dr. House, Dr. Leyenaar, and Dr. Breuner had no disclosures. No external funding was noted for the study.

ANAHEIM, CALIF. – A modular digital intervention to teach mental health skills to youth awaiting transfer to psychiatric care appeared feasible to implement and acceptable to teens and their parents, according to a study presented at the American Academy of Pediatrics National Conference.

“This program has the potential to teach evidence-based mental health skills to youth during boarding, providing a head start on recovery prior to psychiatric hospitalization,” study coauthor Samantha House, DO, MPH, section chief of pediatric hospital medicine at Dartmouth Hitchcock Medical Center, Lebanon, N.H., told attendees.

Mental health boarding has become increasingly common as psychiatric care resources have been stretched by a crisis in pediatric mental health that began even before the COVID pandemic. Since youth often don’t receive evidence-based therapies while boarding, Dr. House and her coauthor, JoAnna K. Leyenaar, MD, PhD, MPH, developed a pilot program called I-CARE, which stands for Improving Care, Accelerating Recovery and Education.

I-CARE is a digital health intervention that combines videos on a tablet with workbook exercises that teach mental health skills. The seven modules include an introduction and one each on schedule-making, safety planning, psychoeducation, behavioral activation, relaxation skills, and mindfulness skills. Licensed nursing assistants who have received a 6-hour training from a clinical psychologist administer the program and provide safety supervision during boarding.

“I-CARE was designed to be largely self-directed, supported by ‘coaches’ who are not mental health professionals,” Dr. Leyenaar, vice chair of research in the department of pediatrics and an associate professor of pediatrics at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. With this model, the program requires minimal additional resources beyond the tablets and workbooks, and is designed for implementation in settings with few or no mental health professionals, she said.

Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington, Seattle, and an attending physician at Seattle Children’s Hospital, was not involved in the study but was excited to see it.

“I think it’s a really good idea, and I like that it’s being studied,” Dr. Breuner said in an interview. She said the health care and public health system has let down an entire population who data had shown were experiencing mental health problems.

“We knew before the pandemic that behavioral health issues were creeping up slowly with anxiety, depression, suicidal ideation, and, of course, substance use disorders and eating disorders, and not a lot was being done about it,” Dr. Breuner said, and the pandemic exacerbated those issues. ”I don’t know why no one realized that this was going to be the downstream effect of having no socialization for kids for 18 months and limited resources for those who we need desperately to provide care for,” especially BIPOC [Black, Indigenous, and people of color] kids and underresourced kids.

That sentiment is exactly what inspired the creation of the program, according to Dr. Leyenaar.

The I-CARE program was implemented at Dartmouth Hitchcock Medical Center in November 2021 for adolescents aged 12-17 who were boarding because of suicidality or self-harm. The program and study excluded youth with psychosis and other cognitive or behavioral conditions that didn’t fit with the skills taught by the module training.

The researchers qualitatively evaluated the I-CARE program in youth who were offered at least two I-CARE modules and with parents present during boarding.

Twenty-four youth, with a median age of 14, were offered the I-CARE program between November 2021 and April 2022 while boarding for a median 8 days. Most of the patients were female (79%), and a third were transgender or gender diverse. Most were White (83%), and about two-thirds had Medicaid (62.5%). The most common diagnoses among the participants were major depressive disorder (71%) and generalized anxiety disorder (46%). Others included PTSD (29%), restrictive eating disorder (21%), and bipolar disorder (12.5%).

All offered the program completed the first module, and 79% participated in additional modules. The main reason for discontinuation was transfer to another facility, but a few youth either refused to engage with the program or felt they knew the material well enough that they weren’t benefiting from it.

The evaluation involved 16 youth, seven parents, and 17 clinicians. On a Likert scale, the composite score for the program’s appropriateness – suitability, applicability, and meeting needs – was an average 3.7, with a higher rating from clinicians (4.3) and caregivers (3.5) than youth (2.8).

“Some youth felt the intervention was better suited for a younger audience or those with less familiarity with mental health skills, but they acknowledged that the intervention would be helpful and appropriate for others,” Dr. House, who is also an assistant professor of pediatrics at Geisel School of Medicine, said.

Youth rated the acceptability of the program more highly (3.6) and all three groups found it easy to use, with an average feasibility score of 4 across the board. The program’s acceptability received an average score of 4 from parents and clinicians.

”Teens seem to particularly value the psychoeducation module that explains the relationship between thoughts and feelings, as well as the opportunity to develop a personalized safety plan,” Dr. Leyenaar said.

Among the challenges expressed by the participating teens were that the loud sounds and beeping in the hospital made it difficult to practice mindfulness and that they often had to wait for staff to be available to do I-CARE.

“I feel like not many people have been trained yet,” one teen said, “so to have more nurses available to do I-CARE would be helpful.”

Another participant found the coaches helpful. “Sometimes they were my nurse, sometimes they were someone I never met before. … and also, they were all really, really nice,” the teen said.

Another teen regarded the material as “really surface-level mental health stuff” that they thought “could be helpful to other people who are here for the first time.” But others found the content more beneficial.

“The videos were helpful. … I was worried that they weren’t going to be very informative, but they did make sense to me,” one participant said. “They weren’t overcomplicating things. … They weren’t saying anything I didn’t understand, so that was good.”

The researchers next plan to conduct a multisite study to determine the program’s effectiveness in improving health outcomes and reducing suicidal ideation. Dr. House and Dr. Leyenaar are looking at ways to refine the program.

”We may narrow the age range for participants, with an upper age limit of 16, since some older teens said that the modules were best suited for a younger audience,” Dr. Leyenaar said. “We are also discussing how to best support youth who are readmitted to our hospital and have participated in I-CARE previously.”

Dr. Breuner said she would be interested to see, in future studies of the program, whether it reduced the likelihood of inpatient psychiatric stay, the length of psychiatric stay after admission, or the risk of readmission. She also wondered if the program might be offered in languages other than English, whether a version might be specifically designed for BIPOC youth, and whether the researchers had considered offering the intervention to caregivers as well.

The modules are teaching the kids but should they also be teaching the parents? Dr. Breuner wondered. A lot of times, she said, the parents are bringing these kids in because they don’t know what to do and can’t deal with them anymore. Offering modules on the same skills to caregivers would also enable the caregivers to reinforce and reteach the skills to their children, especially if the youth struggled to really take in what the modules were trying to teach.

Dr. Leyenaar said she expects buy-in for a program like this would be high at other institutions, but it’s premature to scale it up until they’ve conducted at least another clinical trial on its effectiveness. The biggest potential barrier to buy-in that Dr. Breuner perceived would be cost.

“It’s always difficult when it costs money” since the hospital needs to train the clinicians who provide the care, Dr. Breuner said, but it’s possible those costs could be offset if the program reduces the risk of readmission or return to the emergency department.

While the overall risk of harms from the intervention are low, Dr. Breuner said it is important to be conscious that the intervention may not necessarily be appropriate for all youth.

“There’s always risk when there’s a trauma background, and you have to be very careful, especially with mindfulness training,” Dr. Breuner said. For those with a history of abuse or other adverse childhood experiences “for someone to get into a very calm, still place can actually be counterproductive.”

Dr. Breuner especially appreciated that the researchers involved the youth and caregivers in the evaluation process. “That the parents expressed positive attitudes is really incredible,” she said.

Dr. House, Dr. Leyenaar, and Dr. Breuner had no disclosures. No external funding was noted for the study.

ANAHEIM, CALIF. – A modular digital intervention to teach mental health skills to youth awaiting transfer to psychiatric care appeared feasible to implement and acceptable to teens and their parents, according to a study presented at the American Academy of Pediatrics National Conference.

“This program has the potential to teach evidence-based mental health skills to youth during boarding, providing a head start on recovery prior to psychiatric hospitalization,” study coauthor Samantha House, DO, MPH, section chief of pediatric hospital medicine at Dartmouth Hitchcock Medical Center, Lebanon, N.H., told attendees.

Mental health boarding has become increasingly common as psychiatric care resources have been stretched by a crisis in pediatric mental health that began even before the COVID pandemic. Since youth often don’t receive evidence-based therapies while boarding, Dr. House and her coauthor, JoAnna K. Leyenaar, MD, PhD, MPH, developed a pilot program called I-CARE, which stands for Improving Care, Accelerating Recovery and Education.

I-CARE is a digital health intervention that combines videos on a tablet with workbook exercises that teach mental health skills. The seven modules include an introduction and one each on schedule-making, safety planning, psychoeducation, behavioral activation, relaxation skills, and mindfulness skills. Licensed nursing assistants who have received a 6-hour training from a clinical psychologist administer the program and provide safety supervision during boarding.

“I-CARE was designed to be largely self-directed, supported by ‘coaches’ who are not mental health professionals,” Dr. Leyenaar, vice chair of research in the department of pediatrics and an associate professor of pediatrics at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. With this model, the program requires minimal additional resources beyond the tablets and workbooks, and is designed for implementation in settings with few or no mental health professionals, she said.

Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington, Seattle, and an attending physician at Seattle Children’s Hospital, was not involved in the study but was excited to see it.

“I think it’s a really good idea, and I like that it’s being studied,” Dr. Breuner said in an interview. She said the health care and public health system has let down an entire population who data had shown were experiencing mental health problems.

“We knew before the pandemic that behavioral health issues were creeping up slowly with anxiety, depression, suicidal ideation, and, of course, substance use disorders and eating disorders, and not a lot was being done about it,” Dr. Breuner said, and the pandemic exacerbated those issues. ”I don’t know why no one realized that this was going to be the downstream effect of having no socialization for kids for 18 months and limited resources for those who we need desperately to provide care for,” especially BIPOC [Black, Indigenous, and people of color] kids and underresourced kids.

That sentiment is exactly what inspired the creation of the program, according to Dr. Leyenaar.

The I-CARE program was implemented at Dartmouth Hitchcock Medical Center in November 2021 for adolescents aged 12-17 who were boarding because of suicidality or self-harm. The program and study excluded youth with psychosis and other cognitive or behavioral conditions that didn’t fit with the skills taught by the module training.

The researchers qualitatively evaluated the I-CARE program in youth who were offered at least two I-CARE modules and with parents present during boarding.

Twenty-four youth, with a median age of 14, were offered the I-CARE program between November 2021 and April 2022 while boarding for a median 8 days. Most of the patients were female (79%), and a third were transgender or gender diverse. Most were White (83%), and about two-thirds had Medicaid (62.5%). The most common diagnoses among the participants were major depressive disorder (71%) and generalized anxiety disorder (46%). Others included PTSD (29%), restrictive eating disorder (21%), and bipolar disorder (12.5%).

All offered the program completed the first module, and 79% participated in additional modules. The main reason for discontinuation was transfer to another facility, but a few youth either refused to engage with the program or felt they knew the material well enough that they weren’t benefiting from it.

The evaluation involved 16 youth, seven parents, and 17 clinicians. On a Likert scale, the composite score for the program’s appropriateness – suitability, applicability, and meeting needs – was an average 3.7, with a higher rating from clinicians (4.3) and caregivers (3.5) than youth (2.8).

“Some youth felt the intervention was better suited for a younger audience or those with less familiarity with mental health skills, but they acknowledged that the intervention would be helpful and appropriate for others,” Dr. House, who is also an assistant professor of pediatrics at Geisel School of Medicine, said.

Youth rated the acceptability of the program more highly (3.6) and all three groups found it easy to use, with an average feasibility score of 4 across the board. The program’s acceptability received an average score of 4 from parents and clinicians.

”Teens seem to particularly value the psychoeducation module that explains the relationship between thoughts and feelings, as well as the opportunity to develop a personalized safety plan,” Dr. Leyenaar said.

Among the challenges expressed by the participating teens were that the loud sounds and beeping in the hospital made it difficult to practice mindfulness and that they often had to wait for staff to be available to do I-CARE.

“I feel like not many people have been trained yet,” one teen said, “so to have more nurses available to do I-CARE would be helpful.”

Another participant found the coaches helpful. “Sometimes they were my nurse, sometimes they were someone I never met before. … and also, they were all really, really nice,” the teen said.

Another teen regarded the material as “really surface-level mental health stuff” that they thought “could be helpful to other people who are here for the first time.” But others found the content more beneficial.

“The videos were helpful. … I was worried that they weren’t going to be very informative, but they did make sense to me,” one participant said. “They weren’t overcomplicating things. … They weren’t saying anything I didn’t understand, so that was good.”

The researchers next plan to conduct a multisite study to determine the program’s effectiveness in improving health outcomes and reducing suicidal ideation. Dr. House and Dr. Leyenaar are looking at ways to refine the program.

”We may narrow the age range for participants, with an upper age limit of 16, since some older teens said that the modules were best suited for a younger audience,” Dr. Leyenaar said. “We are also discussing how to best support youth who are readmitted to our hospital and have participated in I-CARE previously.”

Dr. Breuner said she would be interested to see, in future studies of the program, whether it reduced the likelihood of inpatient psychiatric stay, the length of psychiatric stay after admission, or the risk of readmission. She also wondered if the program might be offered in languages other than English, whether a version might be specifically designed for BIPOC youth, and whether the researchers had considered offering the intervention to caregivers as well.

The modules are teaching the kids but should they also be teaching the parents? Dr. Breuner wondered. A lot of times, she said, the parents are bringing these kids in because they don’t know what to do and can’t deal with them anymore. Offering modules on the same skills to caregivers would also enable the caregivers to reinforce and reteach the skills to their children, especially if the youth struggled to really take in what the modules were trying to teach.

Dr. Leyenaar said she expects buy-in for a program like this would be high at other institutions, but it’s premature to scale it up until they’ve conducted at least another clinical trial on its effectiveness. The biggest potential barrier to buy-in that Dr. Breuner perceived would be cost.

“It’s always difficult when it costs money” since the hospital needs to train the clinicians who provide the care, Dr. Breuner said, but it’s possible those costs could be offset if the program reduces the risk of readmission or return to the emergency department.

While the overall risk of harms from the intervention are low, Dr. Breuner said it is important to be conscious that the intervention may not necessarily be appropriate for all youth.

“There’s always risk when there’s a trauma background, and you have to be very careful, especially with mindfulness training,” Dr. Breuner said. For those with a history of abuse or other adverse childhood experiences “for someone to get into a very calm, still place can actually be counterproductive.”

Dr. Breuner especially appreciated that the researchers involved the youth and caregivers in the evaluation process. “That the parents expressed positive attitudes is really incredible,” she said.

Dr. House, Dr. Leyenaar, and Dr. Breuner had no disclosures. No external funding was noted for the study.

In 2019 the Defense Advanced Research Projects Agency invested $27 million in the Focused Pharma program to develop new, more efficacious, rapid-acting drugs, including hallucinogens.¹ While Focused Pharma does not include human studies, the Veterans Health Administration’s (VHA) newly launched psychedelics program research does include clinical trials.² When I read of these ambitious projects, I recalled 2 prescient memories from my youth.

The first memory was of a dinner table conversation between my father, then chief of pediatrics at a military hospital, and one of my older brothers, a burgeoning hippie. My father mentioned that the military was doing research on lysergic acid diethylamide (LSD), and my brother asked whether he could bring some home for my brother to try. My father looked up from the dinner table with incredulity and in an ironic monotone replied, “No you would not qualify for the research, you are not in the Army.”

The second was about 10 years later, when I visited the state psychiatric hospital where my father directed the adolescent ward. I saw a group of young adults watching test patterns on an old-fashioned television set. When I asked my father what was wrong with them, he shook his head and said, “Too much LSD.”

Albert Hoffman was a Sandoz chemist when in 1938 he serendipitously developed LSD while working on a fungus that grew on grain. LSD’s psychoactive properties were not discovered until 1943. About a decade later, as the Cold War chilled international relations, the Central Intelligence Agency (CIA) began conducting experiments on military personnel in the MKUltra program using LSD, electroshock, hypnosis, and other techniques to develop a mind control program before its rivals did.³

Beginning in the 1950s, the US government collaborated with pharmaceutical companies and research universities to develop LSD as part of a campaign of psychological warfare. Though planned to be used against enemies, the program instead exploited US service members to develop hallucinogens as a form of chemical warfare that could render enemy troops mentally incapacitated. That psychiatrists, who then (as now) led much of this research, raised a host of ethical concerns about dual roles, disclosure, and duty.⁴

Government investigations and academic studies have shown that even soldiers who volunteered for the research were not given adequate information about the nature of the experiments and the potential adverse effects, such as persisting flashbacks. The military’s research on LSD ended in 1963, not because of the unethical aspects of the research, but because the effects of LSD were so unpredictable that the drug could not be effectively weaponized. Like Tuskegee and other research abuses of the time, when the MKUltra program was exposed, there were congressional investigations.⁵ Later studies found that many of the active-duty research subjects experienced a plethora of lasting and serious psychiatric symptoms. VHA practitioners had to put back together many of these broken service members. This program was rife with violations of research ethics and human rights, and those abuses tainted the field of hallucinogenic research in US Department of Defense (DoD) and VHA circles for decades.⁵ These research abuses, in part, have led to hallucinogens being categorized as Schedule I controlled substances, effectively blocking federal funding for research until recently.

LSD, Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and 3,4-methylenedioxy-methamphetamine (MDMA), popularly known as psychedelics, are again receiving attention. However, the current investigations into psychedelics are vastly different—scientifically and ethically. The most important difference is that the context and leadership of these studies is not national security—it is health care.

The goal of this new wave of psychedelic research is not mind control or brain alteration, but liberation of the mind from cycles of rumination and trauma and empowerment to change patterns of self-destruction to affirmation of life. The impetus for this research is not international espionage but to find better treatments for chronic posttraumatic stress disorder, severe substance use disorders, and treatment-resistant depression that contribute to unquantifiable mental pain, psychosocial dysfunction, and an epidemic of suicide among military service members and veterans.⁶ Though we have some effective treatments for these often combat-inflicted maladies—primarily evidence-based psychotherapies—yet these treatments are not tolerable or safe, fast-acting, or long-lasting enough to succor each and every troubled soul. The success of ketamine, a dissociative drug, in relieving the most distressing service-connected psychiatric diagnoses has provided a proof of concept to reinvigorate the moribund hallucinogenic research idea.⁷

This dark chapter in US military research is a cautionary tale. The often quoted and more often ignored advice of the Spanish American philosopher George Santayana, “Those who cannot remember the past are condemned to repeat it,” should serve as the guiding principle of the new hallucinogenic research.⁸ Human subjects’ protections have exponentially improved since the days of the secret LSD project even for active-duty personnel. The Common Rule governs that all research participants are given adequate information that includes whatever is known about the risks and benefits of the research.¹⁰ Participants must provide full and free informed consent to enroll in these clinical trials, a consent that encompasses the right to withdraw from the research at any time without jeopardizing their careers, benefits, or ongoing health care.¹⁰

These rules, though, can be bent, broken, avoided, or worked around. Only the moral integrity of study personnel, administrators, oversight agencies, research compliance officers, and most important, principal investigators can assure that the rules are upheld and the rights they guarantee are respected.⁹ It would be a tragic shame if the promised hope for the relief of psychic pain went unrealized due to media hype, shared desperation of clinicians and patients, and conflicts of interests that today are more likely to come from profit-driven pharmaceutical companies than national security agencies. And for all of us in federal practice, remembering the sordid past forays with LSD can redeem the present research so future service members and veterans and the clinicians who care for them have better balms to heal the wounds of war.

In 2019 the Defense Advanced Research Projects Agency invested $27 million in the Focused Pharma program to develop new, more efficacious, rapid-acting drugs, including hallucinogens.¹ While Focused Pharma does not include human studies, the Veterans Health Administration’s (VHA) newly launched psychedelics program research does include clinical trials.² When I read of these ambitious projects, I recalled 2 prescient memories from my youth.

The first memory was of a dinner table conversation between my father, then chief of pediatrics at a military hospital, and one of my older brothers, a burgeoning hippie. My father mentioned that the military was doing research on lysergic acid diethylamide (LSD), and my brother asked whether he could bring some home for my brother to try. My father looked up from the dinner table with incredulity and in an ironic monotone replied, “No you would not qualify for the research, you are not in the Army.”

The second was about 10 years later, when I visited the state psychiatric hospital where my father directed the adolescent ward. I saw a group of young adults watching test patterns on an old-fashioned television set. When I asked my father what was wrong with them, he shook his head and said, “Too much LSD.”

Albert Hoffman was a Sandoz chemist when in 1938 he serendipitously developed LSD while working on a fungus that grew on grain. LSD’s psychoactive properties were not discovered until 1943. About a decade later, as the Cold War chilled international relations, the Central Intelligence Agency (CIA) began conducting experiments on military personnel in the MKUltra program using LSD, electroshock, hypnosis, and other techniques to develop a mind control program before its rivals did.³

Beginning in the 1950s, the US government collaborated with pharmaceutical companies and research universities to develop LSD as part of a campaign of psychological warfare. Though planned to be used against enemies, the program instead exploited US service members to develop hallucinogens as a form of chemical warfare that could render enemy troops mentally incapacitated. That psychiatrists, who then (as now) led much of this research, raised a host of ethical concerns about dual roles, disclosure, and duty.⁴

Government investigations and academic studies have shown that even soldiers who volunteered for the research were not given adequate information about the nature of the experiments and the potential adverse effects, such as persisting flashbacks. The military’s research on LSD ended in 1963, not because of the unethical aspects of the research, but because the effects of LSD were so unpredictable that the drug could not be effectively weaponized. Like Tuskegee and other research abuses of the time, when the MKUltra program was exposed, there were congressional investigations.⁵ Later studies found that many of the active-duty research subjects experienced a plethora of lasting and serious psychiatric symptoms. VHA practitioners had to put back together many of these broken service members. This program was rife with violations of research ethics and human rights, and those abuses tainted the field of hallucinogenic research in US Department of Defense (DoD) and VHA circles for decades.⁵ These research abuses, in part, have led to hallucinogens being categorized as Schedule I controlled substances, effectively blocking federal funding for research until recently.

LSD, Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and 3,4-methylenedioxy-methamphetamine (MDMA), popularly known as psychedelics, are again receiving attention. However, the current investigations into psychedelics are vastly different—scientifically and ethically. The most important difference is that the context and leadership of these studies is not national security—it is health care.

The goal of this new wave of psychedelic research is not mind control or brain alteration, but liberation of the mind from cycles of rumination and trauma and empowerment to change patterns of self-destruction to affirmation of life. The impetus for this research is not international espionage but to find better treatments for chronic posttraumatic stress disorder, severe substance use disorders, and treatment-resistant depression that contribute to unquantifiable mental pain, psychosocial dysfunction, and an epidemic of suicide among military service members and veterans.⁶ Though we have some effective treatments for these often combat-inflicted maladies—primarily evidence-based psychotherapies—yet these treatments are not tolerable or safe, fast-acting, or long-lasting enough to succor each and every troubled soul. The success of ketamine, a dissociative drug, in relieving the most distressing service-connected psychiatric diagnoses has provided a proof of concept to reinvigorate the moribund hallucinogenic research idea.⁷

This dark chapter in US military research is a cautionary tale. The often quoted and more often ignored advice of the Spanish American philosopher George Santayana, “Those who cannot remember the past are condemned to repeat it,” should serve as the guiding principle of the new hallucinogenic research.⁸ Human subjects’ protections have exponentially improved since the days of the secret LSD project even for active-duty personnel. The Common Rule governs that all research participants are given adequate information that includes whatever is known about the risks and benefits of the research.¹⁰ Participants must provide full and free informed consent to enroll in these clinical trials, a consent that encompasses the right to withdraw from the research at any time without jeopardizing their careers, benefits, or ongoing health care.¹⁰

These rules, though, can be bent, broken, avoided, or worked around. Only the moral integrity of study personnel, administrators, oversight agencies, research compliance officers, and most important, principal investigators can assure that the rules are upheld and the rights they guarantee are respected.⁹ It would be a tragic shame if the promised hope for the relief of psychic pain went unrealized due to media hype, shared desperation of clinicians and patients, and conflicts of interests that today are more likely to come from profit-driven pharmaceutical companies than national security agencies. And for all of us in federal practice, remembering the sordid past forays with LSD can redeem the present research so future service members and veterans and the clinicians who care for them have better balms to heal the wounds of war.

In 2019 the Defense Advanced Research Projects Agency invested $27 million in the Focused Pharma program to develop new, more efficacious, rapid-acting drugs, including hallucinogens.¹ While Focused Pharma does not include human studies, the Veterans Health Administration’s (VHA) newly launched psychedelics program research does include clinical trials.² When I read of these ambitious projects, I recalled 2 prescient memories from my youth.

The first memory was of a dinner table conversation between my father, then chief of pediatrics at a military hospital, and one of my older brothers, a burgeoning hippie. My father mentioned that the military was doing research on lysergic acid diethylamide (LSD), and my brother asked whether he could bring some home for my brother to try. My father looked up from the dinner table with incredulity and in an ironic monotone replied, “No you would not qualify for the research, you are not in the Army.”

The second was about 10 years later, when I visited the state psychiatric hospital where my father directed the adolescent ward. I saw a group of young adults watching test patterns on an old-fashioned television set. When I asked my father what was wrong with them, he shook his head and said, “Too much LSD.”

Albert Hoffman was a Sandoz chemist when in 1938 he serendipitously developed LSD while working on a fungus that grew on grain. LSD’s psychoactive properties were not discovered until 1943. About a decade later, as the Cold War chilled international relations, the Central Intelligence Agency (CIA) began conducting experiments on military personnel in the MKUltra program using LSD, electroshock, hypnosis, and other techniques to develop a mind control program before its rivals did.³

Beginning in the 1950s, the US government collaborated with pharmaceutical companies and research universities to develop LSD as part of a campaign of psychological warfare. Though planned to be used against enemies, the program instead exploited US service members to develop hallucinogens as a form of chemical warfare that could render enemy troops mentally incapacitated. That psychiatrists, who then (as now) led much of this research, raised a host of ethical concerns about dual roles, disclosure, and duty.⁴

Government investigations and academic studies have shown that even soldiers who volunteered for the research were not given adequate information about the nature of the experiments and the potential adverse effects, such as persisting flashbacks. The military’s research on LSD ended in 1963, not because of the unethical aspects of the research, but because the effects of LSD were so unpredictable that the drug could not be effectively weaponized. Like Tuskegee and other research abuses of the time, when the MKUltra program was exposed, there were congressional investigations.⁵ Later studies found that many of the active-duty research subjects experienced a plethora of lasting and serious psychiatric symptoms. VHA practitioners had to put back together many of these broken service members. This program was rife with violations of research ethics and human rights, and those abuses tainted the field of hallucinogenic research in US Department of Defense (DoD) and VHA circles for decades.⁵ These research abuses, in part, have led to hallucinogens being categorized as Schedule I controlled substances, effectively blocking federal funding for research until recently.

LSD, Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and 3,4-methylenedioxy-methamphetamine (MDMA), popularly known as psychedelics, are again receiving attention. However, the current investigations into psychedelics are vastly different—scientifically and ethically. The most important difference is that the context and leadership of these studies is not national security—it is health care.

The goal of this new wave of psychedelic research is not mind control or brain alteration, but liberation of the mind from cycles of rumination and trauma and empowerment to change patterns of self-destruction to affirmation of life. The impetus for this research is not international espionage but to find better treatments for chronic posttraumatic stress disorder, severe substance use disorders, and treatment-resistant depression that contribute to unquantifiable mental pain, psychosocial dysfunction, and an epidemic of suicide among military service members and veterans.⁶ Though we have some effective treatments for these often combat-inflicted maladies—primarily evidence-based psychotherapies—yet these treatments are not tolerable or safe, fast-acting, or long-lasting enough to succor each and every troubled soul. The success of ketamine, a dissociative drug, in relieving the most distressing service-connected psychiatric diagnoses has provided a proof of concept to reinvigorate the moribund hallucinogenic research idea.⁷

This dark chapter in US military research is a cautionary tale. The often quoted and more often ignored advice of the Spanish American philosopher George Santayana, “Those who cannot remember the past are condemned to repeat it,” should serve as the guiding principle of the new hallucinogenic research.⁸ Human subjects’ protections have exponentially improved since the days of the secret LSD project even for active-duty personnel. The Common Rule governs that all research participants are given adequate information that includes whatever is known about the risks and benefits of the research.¹⁰ Participants must provide full and free informed consent to enroll in these clinical trials, a consent that encompasses the right to withdraw from the research at any time without jeopardizing their careers, benefits, or ongoing health care.¹⁰

These rules, though, can be bent, broken, avoided, or worked around. Only the moral integrity of study personnel, administrators, oversight agencies, research compliance officers, and most important, principal investigators can assure that the rules are upheld and the rights they guarantee are respected.⁹ It would be a tragic shame if the promised hope for the relief of psychic pain went unrealized due to media hype, shared desperation of clinicians and patients, and conflicts of interests that today are more likely to come from profit-driven pharmaceutical companies than national security agencies. And for all of us in federal practice, remembering the sordid past forays with LSD can redeem the present research so future service members and veterans and the clinicians who care for them have better balms to heal the wounds of war.

The U.S. Preventive Services Task Force on Oct. 11 posted final recommendations on screening for anxiety, depression, and suicide risk in children and adolescents.

For the first time, the task force recommended screening for anxiety in children aged 8-18 years who do not have a diagnosed anxiety disorder and are not showing signs or symptoms of anxiety.

This “B” recommendation reflects “moderate certainty” evidence that screening for anxiety in 8- to 18-year-olds has a moderate net benefit, the task force said.

However, the task force found “insufficient” evidence to weigh the balance of benefits and harms of screening for anxiety in children aged 7 and younger and therefore issued an “I” statement.

The task force also recommended screening for children aged 12-18 years for major depressive disorder (“B” recommendation) but said there is insufficient evidence to weigh the balance of benefits and harms of screening for depression in children aged 11 and younger (“I” statement). 

These recommendations are in line with the 2016 recommendations on depression screening from the USPSTF.

“Fortunately, screening older children for anxiety and depression can identify these conditions so children and teens can receive the care that they need,” task force member Martha Kubik, PhD, RN, with George Mason University, Fairfax, Va., said in a statement.

“Unfortunately, there are key evidence gaps related to screening for anxiety and depression in younger children and screening for suicide risk in all youth,” added task force member Lori Pbert, PhD, University of Massachusetts, Worcester.

“We are calling for more research in these critical areas so we can provide health care professionals with evidence-based ways to keep their young patients healthy,” Dr. Pbert said.
 

Suicide screening

Turning to suicide, the task force says there is not enough evidence to recommend for or against screening for suicide risk in children and adolescents, and therefore issued an “I” statement – in line with the 2014 recommendation statement from the task force.

The task force acknowledged that the American Academy of Pediatrics, the American Foundation for Suicide Prevention, and experts from the National Institute of Mental Health have released a “Blueprint for Youth Suicide Prevention” that recommends universal screening for suicide risk in youth 12 years or older, while children aged 8-11 years should be screened as clinically indicated.

The task force’s final recommendation statements and corresponding evidence summaries on screening children and adolescents for anxiety, depression and suicide were published online Oct. 11, 2022, in JAMA and the USPSTF website.

The final recommendations are consistent with the 2022 draft recommendation statements on these topics.

The task force emphasized that screening is only the first step in helping children and adolescents with anxiety and depression. Youth who screen positive need further evaluation to determine if they have anxiety or depression.

After diagnosis, youth should participate in shared decision-making with their parents and healthcare professional to identify the best treatment or combination of treatments.
 

Only a first step

In an accompanying editorial, John Walkup, MD, with Ann and Robert H. Lurie Children’s Hospital, Chicago, and coauthors made the point that, for the potential of screening for pediatric anxiety disorders to be fully realized, research focused on the process of screening from evaluation to treatment needs to be a priority.

“Perhaps most critical is developing a smart and sophisticated process of screening aligned with evidence-based treatment strategies that brings added value to routine pediatric medical care and that improves physical and mental health outcomes for children and adolescents,” they wrote.

Members of the USPSTF disclosed no relevant financial relationships. Dr. Walkup reported serving as an unpaid member of the scientific council of the Anxiety and Depression Association of America, receiving royalties for anxiety-related continuing medical education activities from Wolters Kluwer and honoraria for anxiety presentations from the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics.

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

The U.S. Preventive Services Task Force on Oct. 11 posted final recommendations on screening for anxiety, depression, and suicide risk in children and adolescents.

For the first time, the task force recommended screening for anxiety in children aged 8-18 years who do not have a diagnosed anxiety disorder and are not showing signs or symptoms of anxiety.

This “B” recommendation reflects “moderate certainty” evidence that screening for anxiety in 8- to 18-year-olds has a moderate net benefit, the task force said.

However, the task force found “insufficient” evidence to weigh the balance of benefits and harms of screening for anxiety in children aged 7 and younger and therefore issued an “I” statement.

The task force also recommended screening for children aged 12-18 years for major depressive disorder (“B” recommendation) but said there is insufficient evidence to weigh the balance of benefits and harms of screening for depression in children aged 11 and younger (“I” statement). 

These recommendations are in line with the 2016 recommendations on depression screening from the USPSTF.

“Fortunately, screening older children for anxiety and depression can identify these conditions so children and teens can receive the care that they need,” task force member Martha Kubik, PhD, RN, with George Mason University, Fairfax, Va., said in a statement.

“Unfortunately, there are key evidence gaps related to screening for anxiety and depression in younger children and screening for suicide risk in all youth,” added task force member Lori Pbert, PhD, University of Massachusetts, Worcester.

“We are calling for more research in these critical areas so we can provide health care professionals with evidence-based ways to keep their young patients healthy,” Dr. Pbert said.
 

Suicide screening

Turning to suicide, the task force says there is not enough evidence to recommend for or against screening for suicide risk in children and adolescents, and therefore issued an “I” statement – in line with the 2014 recommendation statement from the task force.

The task force acknowledged that the American Academy of Pediatrics, the American Foundation for Suicide Prevention, and experts from the National Institute of Mental Health have released a “Blueprint for Youth Suicide Prevention” that recommends universal screening for suicide risk in youth 12 years or older, while children aged 8-11 years should be screened as clinically indicated.

The task force’s final recommendation statements and corresponding evidence summaries on screening children and adolescents for anxiety, depression and suicide were published online Oct. 11, 2022, in JAMA and the USPSTF website.

The final recommendations are consistent with the 2022 draft recommendation statements on these topics.

The task force emphasized that screening is only the first step in helping children and adolescents with anxiety and depression. Youth who screen positive need further evaluation to determine if they have anxiety or depression.

After diagnosis, youth should participate in shared decision-making with their parents and healthcare professional to identify the best treatment or combination of treatments.
 

Only a first step

In an accompanying editorial, John Walkup, MD, with Ann and Robert H. Lurie Children’s Hospital, Chicago, and coauthors made the point that, for the potential of screening for pediatric anxiety disorders to be fully realized, research focused on the process of screening from evaluation to treatment needs to be a priority.

“Perhaps most critical is developing a smart and sophisticated process of screening aligned with evidence-based treatment strategies that brings added value to routine pediatric medical care and that improves physical and mental health outcomes for children and adolescents,” they wrote.

Members of the USPSTF disclosed no relevant financial relationships. Dr. Walkup reported serving as an unpaid member of the scientific council of the Anxiety and Depression Association of America, receiving royalties for anxiety-related continuing medical education activities from Wolters Kluwer and honoraria for anxiety presentations from the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics.

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

The U.S. Preventive Services Task Force on Oct. 11 posted final recommendations on screening for anxiety, depression, and suicide risk in children and adolescents.

For the first time, the task force recommended screening for anxiety in children aged 8-18 years who do not have a diagnosed anxiety disorder and are not showing signs or symptoms of anxiety.

This “B” recommendation reflects “moderate certainty” evidence that screening for anxiety in 8- to 18-year-olds has a moderate net benefit, the task force said.

However, the task force found “insufficient” evidence to weigh the balance of benefits and harms of screening for anxiety in children aged 7 and younger and therefore issued an “I” statement.

The task force also recommended screening for children aged 12-18 years for major depressive disorder (“B” recommendation) but said there is insufficient evidence to weigh the balance of benefits and harms of screening for depression in children aged 11 and younger (“I” statement). 

These recommendations are in line with the 2016 recommendations on depression screening from the USPSTF.

“Fortunately, screening older children for anxiety and depression can identify these conditions so children and teens can receive the care that they need,” task force member Martha Kubik, PhD, RN, with George Mason University, Fairfax, Va., said in a statement.

“Unfortunately, there are key evidence gaps related to screening for anxiety and depression in younger children and screening for suicide risk in all youth,” added task force member Lori Pbert, PhD, University of Massachusetts, Worcester.

“We are calling for more research in these critical areas so we can provide health care professionals with evidence-based ways to keep their young patients healthy,” Dr. Pbert said.
 

Suicide screening

Turning to suicide, the task force says there is not enough evidence to recommend for or against screening for suicide risk in children and adolescents, and therefore issued an “I” statement – in line with the 2014 recommendation statement from the task force.

The task force acknowledged that the American Academy of Pediatrics, the American Foundation for Suicide Prevention, and experts from the National Institute of Mental Health have released a “Blueprint for Youth Suicide Prevention” that recommends universal screening for suicide risk in youth 12 years or older, while children aged 8-11 years should be screened as clinically indicated.

The task force’s final recommendation statements and corresponding evidence summaries on screening children and adolescents for anxiety, depression and suicide were published online Oct. 11, 2022, in JAMA and the USPSTF website.

The final recommendations are consistent with the 2022 draft recommendation statements on these topics.

The task force emphasized that screening is only the first step in helping children and adolescents with anxiety and depression. Youth who screen positive need further evaluation to determine if they have anxiety or depression.

After diagnosis, youth should participate in shared decision-making with their parents and healthcare professional to identify the best treatment or combination of treatments.
 

Only a first step

In an accompanying editorial, John Walkup, MD, with Ann and Robert H. Lurie Children’s Hospital, Chicago, and coauthors made the point that, for the potential of screening for pediatric anxiety disorders to be fully realized, research focused on the process of screening from evaluation to treatment needs to be a priority.

“Perhaps most critical is developing a smart and sophisticated process of screening aligned with evidence-based treatment strategies that brings added value to routine pediatric medical care and that improves physical and mental health outcomes for children and adolescents,” they wrote.

Members of the USPSTF disclosed no relevant financial relationships. Dr. Walkup reported serving as an unpaid member of the scientific council of the Anxiety and Depression Association of America, receiving royalties for anxiety-related continuing medical education activities from Wolters Kluwer and honoraria for anxiety presentations from the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics.

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

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

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

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

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

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

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