Mental Health

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Elevated depressive symptoms were associated with an additional brain age of nearly 3 years, based on data from more than 600 individuals.

Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.

Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.

The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.

In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).

The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.

Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.

The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.

However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.

In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.

The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

Sleep disturbances are consistently high throughout the course of psychosis, with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.

For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles – or bursts of brainwave activity during sleep identified by electroencephalography.

“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, told this news organization.

University of Pittsburgh

‘Window of opportunity’

Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).

Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.

Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5,135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1,575 patients and 977 healthy controls.

The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.

The pooled prevalence of sleep disturbances was 50% across clinical stages (95% confidence interval, 40%-61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.

The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases, 48% of the EP group, and 27% of the CP group.

“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Dr. Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”

He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.

“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Dr. Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
 

Altered sleep architecture

To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.

There was a significant standardized mean difference in pooled cases versus controls (SMD, 1.0; 95% CI, 0.7-1.3; P < .001). Each clinical group showed poorer sleep quality, compared with controls.

When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.

Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.

Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.

The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.

They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
 

‘Robust’ spindle results

As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, –1.06), spindle amplitude (SMD, –1.08), and spindle duration (SMD, −1.21), compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.

Dr. Ferrarelli noted the results for spindle abnormalities were among “the most robust” and show that these abnormalities “tend to get worse over the course of the illness.”

The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Dr. Ferrarelli.

“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.

He noted that spindles may also represent a promising target for treatment interventions and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.

Another way to evoke target-brain activity may be through auditory tones – with a patient listening to a particular sound through headphones while asleep, Dr. Ferrarelli said.
 

Reaffirms previous data

Commenting on the study, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”

That so many at-risk study subjects had a sleep abnormality is not surprising, said Dr. Lieberman, who was not involved with the current research.

“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: How distinctive is this from what occurs in people who don’t develop the illness?”

The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Dr. Lieberman.

“But it’s not clear from these results how one would do that,” he added.

The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.

The study was supported by the National Institute of Mental Health. Dr. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Dr. Lieberman has reported no relevant financial relationships.

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

The drug overdose death rate in the United States climbed 376% from 2001 to 2021, with much of that increase occurring in the last 2 years, according to the National Center for Heath Statistics.

The 376% represents the change in age-adjusted overdose deaths per 100,000 population, which went from 6.9 in 2001 to 32.4 in 2021, as the total number of deaths rose from 19,394 to 106,699 (450%) over that time period, the NCHS said in a recent data brief. That total made 2021 the first year ever with more than 100,000 overdose deaths.

Since the age-adjusted rate stood at 21.6 per 100,000 in 2019, that means 42% of the total increase over 20 years actually occurred in 2020 and 2021. The number of deaths increased by about 36,000 over those 2 years, accounting for 41% of the total annual increase from 2001 to 2021, based on data from the National Vital Statistics System mortality files.

The overdose death rate was significantly higher for males than females for all of the years from 2001 to 2021, with males seeing an increase from 9.0 to 45.1 per 100,000 and females going from 4.6 to 19.6 deaths per 100,000. In the single year from 2020 to 2021, the age-adjusted rate was up by 14% for males and 15% for females, the mortality-file data show.

Analysis by age showed an even larger effect in some groups from 2020 to 2021. Drug overdose deaths jumped 28% among adults aged 65 years and older, more than any other group, and by 21% in those aged 55-64 years, according to the NCHS.

The only age group for which deaths didn’t increase significantly from 2020 to 2021 was 15- to 24-year-olds, whose rate rose by just 3%. The age group with the highest rate in both 2020 and 2021, however, was the 35- to 44-year-olds: 53.9 and 62.0 overdose deaths per 100,000, respectively, for an increase of 15%, the NCHS said in the report.

The drugs now involved in overdose deaths are most often opioids, a change from 2001. That year, opioids were involved in 49% of all overdose deaths, but by 2021 that share had increased to 75%. The trend for opioid-related deaths almost matches that of overall deaths over the 20-year span, and the significantly increasing trend that began for all overdose deaths in 2013 closely follows that of synthetic opioids such as fentanyl and tramadol, the report shows.

Overdose deaths involving cocaine and psychostimulants such as methamphetamine, amphetamine, and methylphenidate also show similar increases. The cocaine-related death rate rose 22% from 2020 to 2021 and is up by 421% since 2012, while the corresponding increases for psychostimulant deaths were 33% and 2,400%, the NCHS said.

The drug overdose death rate in the United States climbed 376% from 2001 to 2021, with much of that increase occurring in the last 2 years, according to the National Center for Heath Statistics.

The 376% represents the change in age-adjusted overdose deaths per 100,000 population, which went from 6.9 in 2001 to 32.4 in 2021, as the total number of deaths rose from 19,394 to 106,699 (450%) over that time period, the NCHS said in a recent data brief. That total made 2021 the first year ever with more than 100,000 overdose deaths.

Since the age-adjusted rate stood at 21.6 per 100,000 in 2019, that means 42% of the total increase over 20 years actually occurred in 2020 and 2021. The number of deaths increased by about 36,000 over those 2 years, accounting for 41% of the total annual increase from 2001 to 2021, based on data from the National Vital Statistics System mortality files.

The overdose death rate was significantly higher for males than females for all of the years from 2001 to 2021, with males seeing an increase from 9.0 to 45.1 per 100,000 and females going from 4.6 to 19.6 deaths per 100,000. In the single year from 2020 to 2021, the age-adjusted rate was up by 14% for males and 15% for females, the mortality-file data show.

Analysis by age showed an even larger effect in some groups from 2020 to 2021. Drug overdose deaths jumped 28% among adults aged 65 years and older, more than any other group, and by 21% in those aged 55-64 years, according to the NCHS.

The only age group for which deaths didn’t increase significantly from 2020 to 2021 was 15- to 24-year-olds, whose rate rose by just 3%. The age group with the highest rate in both 2020 and 2021, however, was the 35- to 44-year-olds: 53.9 and 62.0 overdose deaths per 100,000, respectively, for an increase of 15%, the NCHS said in the report.

The drugs now involved in overdose deaths are most often opioids, a change from 2001. That year, opioids were involved in 49% of all overdose deaths, but by 2021 that share had increased to 75%. The trend for opioid-related deaths almost matches that of overall deaths over the 20-year span, and the significantly increasing trend that began for all overdose deaths in 2013 closely follows that of synthetic opioids such as fentanyl and tramadol, the report shows.

Overdose deaths involving cocaine and psychostimulants such as methamphetamine, amphetamine, and methylphenidate also show similar increases. The cocaine-related death rate rose 22% from 2020 to 2021 and is up by 421% since 2012, while the corresponding increases for psychostimulant deaths were 33% and 2,400%, the NCHS said.

The drug overdose death rate in the United States climbed 376% from 2001 to 2021, with much of that increase occurring in the last 2 years, according to the National Center for Heath Statistics.

The 376% represents the change in age-adjusted overdose deaths per 100,000 population, which went from 6.9 in 2001 to 32.4 in 2021, as the total number of deaths rose from 19,394 to 106,699 (450%) over that time period, the NCHS said in a recent data brief. That total made 2021 the first year ever with more than 100,000 overdose deaths.

Since the age-adjusted rate stood at 21.6 per 100,000 in 2019, that means 42% of the total increase over 20 years actually occurred in 2020 and 2021. The number of deaths increased by about 36,000 over those 2 years, accounting for 41% of the total annual increase from 2001 to 2021, based on data from the National Vital Statistics System mortality files.

The overdose death rate was significantly higher for males than females for all of the years from 2001 to 2021, with males seeing an increase from 9.0 to 45.1 per 100,000 and females going from 4.6 to 19.6 deaths per 100,000. In the single year from 2020 to 2021, the age-adjusted rate was up by 14% for males and 15% for females, the mortality-file data show.

Analysis by age showed an even larger effect in some groups from 2020 to 2021. Drug overdose deaths jumped 28% among adults aged 65 years and older, more than any other group, and by 21% in those aged 55-64 years, according to the NCHS.

The only age group for which deaths didn’t increase significantly from 2020 to 2021 was 15- to 24-year-olds, whose rate rose by just 3%. The age group with the highest rate in both 2020 and 2021, however, was the 35- to 44-year-olds: 53.9 and 62.0 overdose deaths per 100,000, respectively, for an increase of 15%, the NCHS said in the report.

The drugs now involved in overdose deaths are most often opioids, a change from 2001. That year, opioids were involved in 49% of all overdose deaths, but by 2021 that share had increased to 75%. The trend for opioid-related deaths almost matches that of overall deaths over the 20-year span, and the significantly increasing trend that began for all overdose deaths in 2013 closely follows that of synthetic opioids such as fentanyl and tramadol, the report shows.

Overdose deaths involving cocaine and psychostimulants such as methamphetamine, amphetamine, and methylphenidate also show similar increases. The cocaine-related death rate rose 22% from 2020 to 2021 and is up by 421% since 2012, while the corresponding increases for psychostimulant deaths were 33% and 2,400%, the NCHS said.

A specific lipid profile can identify patients with schizophrenia, possibly paving the way for the development of the first clinically useful diagnostic test for a severe psychiatric illness, new research suggests.

Although such a test remains a long way off, investigators said, the identification of the unique lipid signature is a critical first step. However, one expert noted that the lipid signature not accurately differentiating patients with schizophrenia from those with bipolar disorder (BD) and major depressive disorder (MDD) limits the findings’ applicability.

The profile includes 77 lipids identified from a large analysis of many different classes of lipid species. Lipids such as cholesterol and triglycerides made up only a small fraction of the classes assessed.

The investigators noted that some of the lipids in the profile associated with schizophrenia are involved in determining cell membrane structure and fluidity or cell-to-cell messaging, which could be important to synaptic function.

“These 77 lipids jointly constitute a lipidomic profile that discriminated between individuals with schizophrenia and individuals without a mental health diagnosis with very high accuracy,” investigator Eva C. Schulte, MD, PhD, of the Institute of Psychiatric Phenomics and Genomics (IPPG) and the department of psychiatry and psychotherapy at University Hospital of Ludwig-Maximilians-University, Munich, told this news organization.

“Of note, we did not see large profile differences between patients with a first psychotic episode who had only been treated for a few days and individuals on long-term antipsychotic therapy,” Dr. Schulte said.

The findings were published online in JAMA Psychiatry.
 

Detailed analysis

Lipid profiles in patients with psychiatric diagnoses have been reported previously, but those studies were small and did not identify a reliable signature independent of demographic and environmental factors.

For the current study, researchers analyzed blood plasma lipid levels from 980 individuals with severe psychiatric illness and 572 people without mental illness from three cohorts in China, Germany, Austria, and Russia.

The study sample included patients with schizophrenia (n = 478), BD (n = 184), and MDD (n = 256), as well as 104 patients with a first psychotic episode who had no long-term psychopharmacology use.

Results showed 77 lipids in 14 classes were significantly altered between participants with schizophrenia and the healthy control in all three cohorts.

The most prominent alterations at the lipid class level included increases in ceramide, triacylglyceride, and phosphatidylcholine and decreases in acylcarnitine and phosphatidylcholine plasmalogen (P < .05 for each cohort).

Schizophrenia-associated lipid differences were similar between patients with high and low symptom severity (P < .001), suggesting that the lipid alterations might represent a trait of the psychiatric disorder.
 

No medication effect

Most patients in the study received long-term antipsychotic medication, which has been shown previously to affect some plasma lipid compounds.

So, to assess a possible effect of medication, the investigators evaluated 13 patients with schizophrenia who were not medicated for at least 6 months prior to blood sample collection and the cohort of patients with a first psychotic episode who had been medicated for less than 1 week.

Comparison of the lipid intensity differences between the healthy controls group and either participants receiving medication or those who were not medicated revealed highly correlated alterations in both patient groups (P < .001).

“Taken together, these results indicate that the identified schizophrenia-associated alterations cannot be attributed to medication effects,” the investigators wrote.

Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were similar to those of schizophrenia but not identical.

Researchers isolated 97 lipids altered in the MDD cohorts and 47 in the BPD cohorts – with 30 and 28, respectively, overlapping with the schizophrenia-associated features and seven of the lipids found among all three disorders.

Although this was significantly more than expected by chance (P < .001), it was not strong enough to demonstrate a clear association, the investigators wrote.

“The profiles were very successful at differentiating individuals with severe mental health conditions from individuals without a diagnosed mental health condition, but much less so at differentiating between the different diagnostic entities,” coinvestigator Thomas G. Schulze, MD, director of IPPG, said in an interview.

“An important caveat, however, is that the available sample sizes for bipolar disorder and major depressive disorder were smaller than those for schizophrenia, which makes a direct comparison between these difficult,” added Dr. Schulze, clinical professor in psychiatry and behavioral sciences at State University of New York, Syracuse.
 

More work remains

Although the study is thought to be the largest to date to examine lipid profiles associated with serious psychiatric illness, much work remains, Dr. Schulze noted.

“At this time, based on these first results, no clinical diagnostic test can be derived from these results,” he said.

He added that the development of reliable biomarkers based on lipidomic profiles would require large prospective randomized trials, complemented by observational studies assessing full lipidomic profiles across the lifespan.

Researchers also need to better understand the exact mechanism by which lipid alterations are associated with schizophrenia and other illnesses.

Physiologically, the investigated lipids have many additional functions, such as determining cell membrane structure and fluidity or cell-to-cell messaging.

Dr. Schulte noted that several lipid species may be involved in determining mechanisms important to synaptic function, such as cell membrane fluidity and vesicle release.

“As is commonly known, alterations in synaptic function underly many severe psychiatric disorders,” she said. “Changes in lipid species could theoretically be related to these synaptic alterations.”
 

A better marker needed

In a comment, Stephen Strakowski, MD, professor and vice chair of research in the department of psychiatry, Indiana University, Indianapolis and Evansville, noted that while the findings are interesting, they don’t really offer the kind of information clinicians who treat patients with serious mental illness need most.

“Do we need a marker to tell us if someone’s got a major mental illness compared to a healthy person?” asked Dr. Strakowski, who was not part of the study. “The answer to that is no. We already know how to do that.”

A truly useful marker would help clinicians differentiate between schizophrenia, bipolar disorder, major depression, or another serious mental illness, he said.

“That’s the marker that would be most helpful,” he added. “This can’t address that, but perhaps it could be a step to start designing a test for that.”

Dr. Strakowksi noted that the findings do not clarify whether the lipid profile found in patients with schizophrenia predates diagnosis or whether it is a result of the mental illness, an unrelated illness, or another factor that could be critical in treating patients.

However, he was quick to point out the limitations don’t diminish the importance of the study.

“It’s a large dataset that’s cross-national, cross-diagnostic that says there appears to be a signal here that there’s something about lipid profiles that may be independent of treatment that could be worth understanding,” Dr. Strakowksi said.

“It allows us to think about developing different models based on lipid profiles, and that’s important,” he added.

The study was funded by the National Key R&D Program of China, National One Thousand Foreign Experts Plan, Moscow Center for Innovative Technologies in Healthcare, European Union’s Horizon 2020 Research and Innovation Programme, NARSAD Young Investigator Grant, German Research Foundation, German Ministry for Education and Research, the Dr. Lisa Oehler Foundation, and the Munich Clinician Scientist Program. Dr. Schulze and Dr. Schulte reported no relevant financial relationships.

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

A specific lipid profile can identify patients with schizophrenia, possibly paving the way for the development of the first clinically useful diagnostic test for a severe psychiatric illness, new research suggests.

Although such a test remains a long way off, investigators said, the identification of the unique lipid signature is a critical first step. However, one expert noted that the lipid signature not accurately differentiating patients with schizophrenia from those with bipolar disorder (BD) and major depressive disorder (MDD) limits the findings’ applicability.

The profile includes 77 lipids identified from a large analysis of many different classes of lipid species. Lipids such as cholesterol and triglycerides made up only a small fraction of the classes assessed.

The investigators noted that some of the lipids in the profile associated with schizophrenia are involved in determining cell membrane structure and fluidity or cell-to-cell messaging, which could be important to synaptic function.

“These 77 lipids jointly constitute a lipidomic profile that discriminated between individuals with schizophrenia and individuals without a mental health diagnosis with very high accuracy,” investigator Eva C. Schulte, MD, PhD, of the Institute of Psychiatric Phenomics and Genomics (IPPG) and the department of psychiatry and psychotherapy at University Hospital of Ludwig-Maximilians-University, Munich, told this news organization.

“Of note, we did not see large profile differences between patients with a first psychotic episode who had only been treated for a few days and individuals on long-term antipsychotic therapy,” Dr. Schulte said.

The findings were published online in JAMA Psychiatry.
 

Detailed analysis

Lipid profiles in patients with psychiatric diagnoses have been reported previously, but those studies were small and did not identify a reliable signature independent of demographic and environmental factors.

For the current study, researchers analyzed blood plasma lipid levels from 980 individuals with severe psychiatric illness and 572 people without mental illness from three cohorts in China, Germany, Austria, and Russia.

The study sample included patients with schizophrenia (n = 478), BD (n = 184), and MDD (n = 256), as well as 104 patients with a first psychotic episode who had no long-term psychopharmacology use.

Results showed 77 lipids in 14 classes were significantly altered between participants with schizophrenia and the healthy control in all three cohorts.

The most prominent alterations at the lipid class level included increases in ceramide, triacylglyceride, and phosphatidylcholine and decreases in acylcarnitine and phosphatidylcholine plasmalogen (P < .05 for each cohort).

Schizophrenia-associated lipid differences were similar between patients with high and low symptom severity (P < .001), suggesting that the lipid alterations might represent a trait of the psychiatric disorder.
 

No medication effect

Most patients in the study received long-term antipsychotic medication, which has been shown previously to affect some plasma lipid compounds.

So, to assess a possible effect of medication, the investigators evaluated 13 patients with schizophrenia who were not medicated for at least 6 months prior to blood sample collection and the cohort of patients with a first psychotic episode who had been medicated for less than 1 week.

Comparison of the lipid intensity differences between the healthy controls group and either participants receiving medication or those who were not medicated revealed highly correlated alterations in both patient groups (P < .001).

“Taken together, these results indicate that the identified schizophrenia-associated alterations cannot be attributed to medication effects,” the investigators wrote.

Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were similar to those of schizophrenia but not identical.

Researchers isolated 97 lipids altered in the MDD cohorts and 47 in the BPD cohorts – with 30 and 28, respectively, overlapping with the schizophrenia-associated features and seven of the lipids found among all three disorders.

Although this was significantly more than expected by chance (P < .001), it was not strong enough to demonstrate a clear association, the investigators wrote.

“The profiles were very successful at differentiating individuals with severe mental health conditions from individuals without a diagnosed mental health condition, but much less so at differentiating between the different diagnostic entities,” coinvestigator Thomas G. Schulze, MD, director of IPPG, said in an interview.

“An important caveat, however, is that the available sample sizes for bipolar disorder and major depressive disorder were smaller than those for schizophrenia, which makes a direct comparison between these difficult,” added Dr. Schulze, clinical professor in psychiatry and behavioral sciences at State University of New York, Syracuse.
 

More work remains

Although the study is thought to be the largest to date to examine lipid profiles associated with serious psychiatric illness, much work remains, Dr. Schulze noted.

“At this time, based on these first results, no clinical diagnostic test can be derived from these results,” he said.

He added that the development of reliable biomarkers based on lipidomic profiles would require large prospective randomized trials, complemented by observational studies assessing full lipidomic profiles across the lifespan.

Researchers also need to better understand the exact mechanism by which lipid alterations are associated with schizophrenia and other illnesses.

Physiologically, the investigated lipids have many additional functions, such as determining cell membrane structure and fluidity or cell-to-cell messaging.

Dr. Schulte noted that several lipid species may be involved in determining mechanisms important to synaptic function, such as cell membrane fluidity and vesicle release.

“As is commonly known, alterations in synaptic function underly many severe psychiatric disorders,” she said. “Changes in lipid species could theoretically be related to these synaptic alterations.”
 

A better marker needed

In a comment, Stephen Strakowski, MD, professor and vice chair of research in the department of psychiatry, Indiana University, Indianapolis and Evansville, noted that while the findings are interesting, they don’t really offer the kind of information clinicians who treat patients with serious mental illness need most.

“Do we need a marker to tell us if someone’s got a major mental illness compared to a healthy person?” asked Dr. Strakowski, who was not part of the study. “The answer to that is no. We already know how to do that.”

A truly useful marker would help clinicians differentiate between schizophrenia, bipolar disorder, major depression, or another serious mental illness, he said.

“That’s the marker that would be most helpful,” he added. “This can’t address that, but perhaps it could be a step to start designing a test for that.”

Dr. Strakowksi noted that the findings do not clarify whether the lipid profile found in patients with schizophrenia predates diagnosis or whether it is a result of the mental illness, an unrelated illness, or another factor that could be critical in treating patients.

However, he was quick to point out the limitations don’t diminish the importance of the study.

“It’s a large dataset that’s cross-national, cross-diagnostic that says there appears to be a signal here that there’s something about lipid profiles that may be independent of treatment that could be worth understanding,” Dr. Strakowksi said.

“It allows us to think about developing different models based on lipid profiles, and that’s important,” he added.

The study was funded by the National Key R&D Program of China, National One Thousand Foreign Experts Plan, Moscow Center for Innovative Technologies in Healthcare, European Union’s Horizon 2020 Research and Innovation Programme, NARSAD Young Investigator Grant, German Research Foundation, German Ministry for Education and Research, the Dr. Lisa Oehler Foundation, and the Munich Clinician Scientist Program. Dr. Schulze and Dr. Schulte reported no relevant financial relationships.

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

A specific lipid profile can identify patients with schizophrenia, possibly paving the way for the development of the first clinically useful diagnostic test for a severe psychiatric illness, new research suggests.

Although such a test remains a long way off, investigators said, the identification of the unique lipid signature is a critical first step. However, one expert noted that the lipid signature not accurately differentiating patients with schizophrenia from those with bipolar disorder (BD) and major depressive disorder (MDD) limits the findings’ applicability.

The profile includes 77 lipids identified from a large analysis of many different classes of lipid species. Lipids such as cholesterol and triglycerides made up only a small fraction of the classes assessed.

The investigators noted that some of the lipids in the profile associated with schizophrenia are involved in determining cell membrane structure and fluidity or cell-to-cell messaging, which could be important to synaptic function.

“These 77 lipids jointly constitute a lipidomic profile that discriminated between individuals with schizophrenia and individuals without a mental health diagnosis with very high accuracy,” investigator Eva C. Schulte, MD, PhD, of the Institute of Psychiatric Phenomics and Genomics (IPPG) and the department of psychiatry and psychotherapy at University Hospital of Ludwig-Maximilians-University, Munich, told this news organization.

“Of note, we did not see large profile differences between patients with a first psychotic episode who had only been treated for a few days and individuals on long-term antipsychotic therapy,” Dr. Schulte said.

The findings were published online in JAMA Psychiatry.
 

Detailed analysis

Lipid profiles in patients with psychiatric diagnoses have been reported previously, but those studies were small and did not identify a reliable signature independent of demographic and environmental factors.

For the current study, researchers analyzed blood plasma lipid levels from 980 individuals with severe psychiatric illness and 572 people without mental illness from three cohorts in China, Germany, Austria, and Russia.

The study sample included patients with schizophrenia (n = 478), BD (n = 184), and MDD (n = 256), as well as 104 patients with a first psychotic episode who had no long-term psychopharmacology use.

Results showed 77 lipids in 14 classes were significantly altered between participants with schizophrenia and the healthy control in all three cohorts.

The most prominent alterations at the lipid class level included increases in ceramide, triacylglyceride, and phosphatidylcholine and decreases in acylcarnitine and phosphatidylcholine plasmalogen (P < .05 for each cohort).

Schizophrenia-associated lipid differences were similar between patients with high and low symptom severity (P < .001), suggesting that the lipid alterations might represent a trait of the psychiatric disorder.
 

No medication effect

Most patients in the study received long-term antipsychotic medication, which has been shown previously to affect some plasma lipid compounds.

So, to assess a possible effect of medication, the investigators evaluated 13 patients with schizophrenia who were not medicated for at least 6 months prior to blood sample collection and the cohort of patients with a first psychotic episode who had been medicated for less than 1 week.

Comparison of the lipid intensity differences between the healthy controls group and either participants receiving medication or those who were not medicated revealed highly correlated alterations in both patient groups (P < .001).

“Taken together, these results indicate that the identified schizophrenia-associated alterations cannot be attributed to medication effects,” the investigators wrote.

Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were similar to those of schizophrenia but not identical.

Researchers isolated 97 lipids altered in the MDD cohorts and 47 in the BPD cohorts – with 30 and 28, respectively, overlapping with the schizophrenia-associated features and seven of the lipids found among all three disorders.

Although this was significantly more than expected by chance (P < .001), it was not strong enough to demonstrate a clear association, the investigators wrote.

“The profiles were very successful at differentiating individuals with severe mental health conditions from individuals without a diagnosed mental health condition, but much less so at differentiating between the different diagnostic entities,” coinvestigator Thomas G. Schulze, MD, director of IPPG, said in an interview.

“An important caveat, however, is that the available sample sizes for bipolar disorder and major depressive disorder were smaller than those for schizophrenia, which makes a direct comparison between these difficult,” added Dr. Schulze, clinical professor in psychiatry and behavioral sciences at State University of New York, Syracuse.
 

More work remains

Although the study is thought to be the largest to date to examine lipid profiles associated with serious psychiatric illness, much work remains, Dr. Schulze noted.

“At this time, based on these first results, no clinical diagnostic test can be derived from these results,” he said.

He added that the development of reliable biomarkers based on lipidomic profiles would require large prospective randomized trials, complemented by observational studies assessing full lipidomic profiles across the lifespan.

Researchers also need to better understand the exact mechanism by which lipid alterations are associated with schizophrenia and other illnesses.

Physiologically, the investigated lipids have many additional functions, such as determining cell membrane structure and fluidity or cell-to-cell messaging.

Dr. Schulte noted that several lipid species may be involved in determining mechanisms important to synaptic function, such as cell membrane fluidity and vesicle release.

“As is commonly known, alterations in synaptic function underly many severe psychiatric disorders,” she said. “Changes in lipid species could theoretically be related to these synaptic alterations.”
 

A better marker needed

In a comment, Stephen Strakowski, MD, professor and vice chair of research in the department of psychiatry, Indiana University, Indianapolis and Evansville, noted that while the findings are interesting, they don’t really offer the kind of information clinicians who treat patients with serious mental illness need most.

“Do we need a marker to tell us if someone’s got a major mental illness compared to a healthy person?” asked Dr. Strakowski, who was not part of the study. “The answer to that is no. We already know how to do that.”

A truly useful marker would help clinicians differentiate between schizophrenia, bipolar disorder, major depression, or another serious mental illness, he said.

“That’s the marker that would be most helpful,” he added. “This can’t address that, but perhaps it could be a step to start designing a test for that.”

Dr. Strakowksi noted that the findings do not clarify whether the lipid profile found in patients with schizophrenia predates diagnosis or whether it is a result of the mental illness, an unrelated illness, or another factor that could be critical in treating patients.

However, he was quick to point out the limitations don’t diminish the importance of the study.

“It’s a large dataset that’s cross-national, cross-diagnostic that says there appears to be a signal here that there’s something about lipid profiles that may be independent of treatment that could be worth understanding,” Dr. Strakowksi said.

“It allows us to think about developing different models based on lipid profiles, and that’s important,” he added.

The study was funded by the National Key R&D Program of China, National One Thousand Foreign Experts Plan, Moscow Center for Innovative Technologies in Healthcare, European Union’s Horizon 2020 Research and Innovation Programme, NARSAD Young Investigator Grant, German Research Foundation, German Ministry for Education and Research, the Dr. Lisa Oehler Foundation, and the Munich Clinician Scientist Program. Dr. Schulze and Dr. Schulte reported no relevant financial relationships.

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

Brain atrophy patterns are similar in individuals with obesity and those with Alzheimer’s disease (AD), a new study shows.

Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.

However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.

“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”

The study was published in the Journal of Alzheimer’s Disease.
 

Cortical Thinning

The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”

The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.

To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.

Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.

The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.

Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.

“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”

Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
 

Lifestyle habits

Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.

The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.

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

Brain atrophy patterns are similar in individuals with obesity and those with Alzheimer’s disease (AD), a new study shows.

Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.

However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.

“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”

The study was published in the Journal of Alzheimer’s Disease.
 

Cortical Thinning

The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”

The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.

To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.

Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.

The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.

Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.

“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”

Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
 

Lifestyle habits

Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.

The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.

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

Brain atrophy patterns are similar in individuals with obesity and those with Alzheimer’s disease (AD), a new study shows.

Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.

However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.

“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”

The study was published in the Journal of Alzheimer’s Disease.
 

Cortical Thinning

The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”

The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.

To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.

Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.

The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.

Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.

“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”

Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
 

Lifestyle habits

Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.

The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.

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

A network of neural connections is linked to six psychiatric disorders: schizophrenia, bipolar disorder (BD), depression, addiction, obsessive-compulsive disorder (OCD), and anxiety, new research shows.

Investigators used coordinate and lesion network mapping to assess whether there was a shared brain network common to multiple psychiatric disorders. In a meta-analysis of almost 200 studies encompassing more than 15,000 individuals, they found that atrophy coordinates across these six psychiatric conditions all mapped to a common brain network.

Moreover, lesion damage to this network in patients with penetrating head trauma correlated with the number of psychiatric illnesses that the patients were diagnosed with post trauma.

The findings have “bigger-picture potential implications,” lead author Joseph Taylor, MD, PhD, medical director of transcranial magnetic stimulation at Brigham and Women’s Hospital’s Center for Brain Circuit Therapeutics, Boston, told this news organization.

“In psychiatry, we talk about symptoms and define our disorders based on symptom checklists, which are fairly reliable but don’t have neurobiological underpinnings,” said Dr. Taylor, who is also an associate psychiatrist in Brigham’s department of psychiatry.

By contrast, “in neurology, we ask: ‘Where is the lesion?’ Studying brain networks could potentially help us diagnose and treat people with psychiatric illness more effectively, just as we treat neurological disorders,” he added.

The findings were published online in Nature Human Behavior.
 

Beyond symptom checklists

Dr. Taylor noted that, in the field of psychiatry, “we often study disorders in isolation,” such as generalized anxiety disorder and major depressive disorder.

“But what see clinically is that half of patients meet the criteria for more than one psychiatric disorder,” he said. “It can be difficult to diagnose and treat these patients, and there are worse treatment outcomes.”

There is also a “discrepancy” between how these disorders are studied (one at a time) and how patients are treated in clinic, Dr. Taylor noted. And there is increasing evidence that psychiatric disorders may share a common neurobiology.

This “highlights the possibility of potentially developing transdiagnostic treatments based on common neurobiology, not just symptom checklists,” Dr. Taylor said.

Prior work “has attempted to map abnormalities to common brain regions rather than to a common brain network,” the investigators wrote. Moreover, “prior studies have rarely tested specificity by comparing psychiatric disorders to other brain disorders.”

In the current study, the researchers used “morphometric brain lesion datasets coupled with a wiring diagram of the human brain to derive a convergent brain network for psychiatric illness.”

They analyzed four large published datasets. Dataset 1 was sourced from an activation likelihood estimation meta-analysis (ALE) of whole-brain voxel-based studies that compared patients with psychiatric disorders such as schizophrenia, BD, depression, addiction, OCD, and anxiety to healthy controls (n = 193 studies; 15,892 individuals in total).

Dataset 2 was drawn from published neuroimaging studies involving patients with Alzheimer’s disease (AD) and other neurodegenerative conditions (n = 72 studies). They reported coordinates regarding which patients with these disorders had more atrophy compared with control persons.

Dataset 3 was sourced from the Vietnam Head Injury study, which followed veterans with and those without penetrating head injuries (n = 194 veterans with injuries). Dataset 4 was sourced from published neurosurgical ablation coordinates for depression.
 

Shared neurobiology

Upon analyzing dataset 1, the researchers found decreased gray matter in the bilateral anterior insula, dorsal anterior cingulate cortex, dorsomedial prefrontal cortex, thalamus, amygdala, hippocampus, and parietal operculum – findings that are “consistent with prior work.”

However, fewer than 35% of the studies contributed to any single cluster; and no cluster was specific to psychiatric versus neurodegenerative coordinates (drawn from dataset 2).

On the other hand, coordinate network mapping yielded “more statistically robust” (P < .001) results, which were found in 85% of the studies. “Psychiatric atrophy coordinates were functionally connected to the same network of brain regions,” the researchers reported.

This network was defined by two types of connectivity, positive and negative.

“The topography of this transdiagnostic network was independent of the statistical threshold and specific to psychiatric (vs. neurodegenerative) disorders, with the strongest peak occurring in the posterior parietal cortex (Brodmann Area 7) near the intraparietal sulcus,” the investigators wrote.

When lesions from dataset 3 were overlaid onto the ALE map and the transdiagnostic network in order to evaluate whether damage to either map correlated with number of post-lesion psychiatric diagnosis, results showed no evidence of a correlation between psychiatric comorbidity and damage on the ALE map (Pearson r, 0.02; P = .766).

However, when the same approach was applied to the transdiagnostic network, a statistically significant correlation was found between psychiatric comorbidity and lesion damage (Pearson r, –0.21; P = .01). A multiple regression model showed that the transdiagnostic, but not the ALE, network “independently predicted the number of post-lesion psychiatric diagnoses” (P = .003 vs. P = .1), the investigators reported.

All four neurosurgical ablative targets for psychiatric disorders found on analysis of dataset 4 “intersected” and aligned with the transdiagnostic network.

“The study does not immediately impact clinical practice, but it would be helpful for practicing clinicians to know that psychiatric disorders commonly co-occur and might share common neurobiology and a convergent brain network,” Dr. Taylor said.

“Future work based on our findings could potentially influence clinical trials and clinical practice, especially in the area of brain stimulation,” he added.
 

‘Exciting new targets’

In a comment, Desmond Oathes, PhD, associate director, Center for Neuromodulation and Stress, University of Pennsylvania, Philadelphia, said the “next step in the science is to combine individual brain imaging, aka, ‘individualized connectomes,’ with these promising group maps to determine something meaningful at the individual patient level.”

Dr. Oathes, who is also a faculty clinician at the Center for the Treatment and Study of Anxiety and was not involved with the study, noted that an open question is whether the brain volume abnormalities/atrophy “can be changed with treatment and in what direction.”

A “strong take-home message from this paper is that brain volume measures from single coordinates are noisy as measures of psychiatric abnormality, whereas network effects seem to be especially sensitive for capturing these effects,” Dr. Oathes said.

The “abnormal networks across these disorders do not fit easily into well-known networks from healthy participants. However, they map well onto other databases relevant to psychiatric disorders and offer exciting new potential targets for prospective treatment studies,” he added.

The investigators received no specific funding for this work. Dr. Taylor reported no relevant financial relationships. Dr. Oathes reported no relevant financial relationships.

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

A network of neural connections is linked to six psychiatric disorders: schizophrenia, bipolar disorder (BD), depression, addiction, obsessive-compulsive disorder (OCD), and anxiety, new research shows.

Investigators used coordinate and lesion network mapping to assess whether there was a shared brain network common to multiple psychiatric disorders. In a meta-analysis of almost 200 studies encompassing more than 15,000 individuals, they found that atrophy coordinates across these six psychiatric conditions all mapped to a common brain network.

Moreover, lesion damage to this network in patients with penetrating head trauma correlated with the number of psychiatric illnesses that the patients were diagnosed with post trauma.

The findings have “bigger-picture potential implications,” lead author Joseph Taylor, MD, PhD, medical director of transcranial magnetic stimulation at Brigham and Women’s Hospital’s Center for Brain Circuit Therapeutics, Boston, told this news organization.

“In psychiatry, we talk about symptoms and define our disorders based on symptom checklists, which are fairly reliable but don’t have neurobiological underpinnings,” said Dr. Taylor, who is also an associate psychiatrist in Brigham’s department of psychiatry.

By contrast, “in neurology, we ask: ‘Where is the lesion?’ Studying brain networks could potentially help us diagnose and treat people with psychiatric illness more effectively, just as we treat neurological disorders,” he added.

The findings were published online in Nature Human Behavior.
 

Beyond symptom checklists

Dr. Taylor noted that, in the field of psychiatry, “we often study disorders in isolation,” such as generalized anxiety disorder and major depressive disorder.

“But what see clinically is that half of patients meet the criteria for more than one psychiatric disorder,” he said. “It can be difficult to diagnose and treat these patients, and there are worse treatment outcomes.”

There is also a “discrepancy” between how these disorders are studied (one at a time) and how patients are treated in clinic, Dr. Taylor noted. And there is increasing evidence that psychiatric disorders may share a common neurobiology.

This “highlights the possibility of potentially developing transdiagnostic treatments based on common neurobiology, not just symptom checklists,” Dr. Taylor said.

Prior work “has attempted to map abnormalities to common brain regions rather than to a common brain network,” the investigators wrote. Moreover, “prior studies have rarely tested specificity by comparing psychiatric disorders to other brain disorders.”

In the current study, the researchers used “morphometric brain lesion datasets coupled with a wiring diagram of the human brain to derive a convergent brain network for psychiatric illness.”

They analyzed four large published datasets. Dataset 1 was sourced from an activation likelihood estimation meta-analysis (ALE) of whole-brain voxel-based studies that compared patients with psychiatric disorders such as schizophrenia, BD, depression, addiction, OCD, and anxiety to healthy controls (n = 193 studies; 15,892 individuals in total).

Dataset 2 was drawn from published neuroimaging studies involving patients with Alzheimer’s disease (AD) and other neurodegenerative conditions (n = 72 studies). They reported coordinates regarding which patients with these disorders had more atrophy compared with control persons.

Dataset 3 was sourced from the Vietnam Head Injury study, which followed veterans with and those without penetrating head injuries (n = 194 veterans with injuries). Dataset 4 was sourced from published neurosurgical ablation coordinates for depression.
 

Shared neurobiology

Upon analyzing dataset 1, the researchers found decreased gray matter in the bilateral anterior insula, dorsal anterior cingulate cortex, dorsomedial prefrontal cortex, thalamus, amygdala, hippocampus, and parietal operculum – findings that are “consistent with prior work.”

However, fewer than 35% of the studies contributed to any single cluster; and no cluster was specific to psychiatric versus neurodegenerative coordinates (drawn from dataset 2).

On the other hand, coordinate network mapping yielded “more statistically robust” (P < .001) results, which were found in 85% of the studies. “Psychiatric atrophy coordinates were functionally connected to the same network of brain regions,” the researchers reported.

This network was defined by two types of connectivity, positive and negative.

“The topography of this transdiagnostic network was independent of the statistical threshold and specific to psychiatric (vs. neurodegenerative) disorders, with the strongest peak occurring in the posterior parietal cortex (Brodmann Area 7) near the intraparietal sulcus,” the investigators wrote.

When lesions from dataset 3 were overlaid onto the ALE map and the transdiagnostic network in order to evaluate whether damage to either map correlated with number of post-lesion psychiatric diagnosis, results showed no evidence of a correlation between psychiatric comorbidity and damage on the ALE map (Pearson r, 0.02; P = .766).

However, when the same approach was applied to the transdiagnostic network, a statistically significant correlation was found between psychiatric comorbidity and lesion damage (Pearson r, –0.21; P = .01). A multiple regression model showed that the transdiagnostic, but not the ALE, network “independently predicted the number of post-lesion psychiatric diagnoses” (P = .003 vs. P = .1), the investigators reported.

All four neurosurgical ablative targets for psychiatric disorders found on analysis of dataset 4 “intersected” and aligned with the transdiagnostic network.

“The study does not immediately impact clinical practice, but it would be helpful for practicing clinicians to know that psychiatric disorders commonly co-occur and might share common neurobiology and a convergent brain network,” Dr. Taylor said.

“Future work based on our findings could potentially influence clinical trials and clinical practice, especially in the area of brain stimulation,” he added.
 

‘Exciting new targets’

In a comment, Desmond Oathes, PhD, associate director, Center for Neuromodulation and Stress, University of Pennsylvania, Philadelphia, said the “next step in the science is to combine individual brain imaging, aka, ‘individualized connectomes,’ with these promising group maps to determine something meaningful at the individual patient level.”

Dr. Oathes, who is also a faculty clinician at the Center for the Treatment and Study of Anxiety and was not involved with the study, noted that an open question is whether the brain volume abnormalities/atrophy “can be changed with treatment and in what direction.”

A “strong take-home message from this paper is that brain volume measures from single coordinates are noisy as measures of psychiatric abnormality, whereas network effects seem to be especially sensitive for capturing these effects,” Dr. Oathes said.

The “abnormal networks across these disorders do not fit easily into well-known networks from healthy participants. However, they map well onto other databases relevant to psychiatric disorders and offer exciting new potential targets for prospective treatment studies,” he added.

The investigators received no specific funding for this work. Dr. Taylor reported no relevant financial relationships. Dr. Oathes reported no relevant financial relationships.

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

A network of neural connections is linked to six psychiatric disorders: schizophrenia, bipolar disorder (BD), depression, addiction, obsessive-compulsive disorder (OCD), and anxiety, new research shows.

Investigators used coordinate and lesion network mapping to assess whether there was a shared brain network common to multiple psychiatric disorders. In a meta-analysis of almost 200 studies encompassing more than 15,000 individuals, they found that atrophy coordinates across these six psychiatric conditions all mapped to a common brain network.

Moreover, lesion damage to this network in patients with penetrating head trauma correlated with the number of psychiatric illnesses that the patients were diagnosed with post trauma.

The findings have “bigger-picture potential implications,” lead author Joseph Taylor, MD, PhD, medical director of transcranial magnetic stimulation at Brigham and Women’s Hospital’s Center for Brain Circuit Therapeutics, Boston, told this news organization.

“In psychiatry, we talk about symptoms and define our disorders based on symptom checklists, which are fairly reliable but don’t have neurobiological underpinnings,” said Dr. Taylor, who is also an associate psychiatrist in Brigham’s department of psychiatry.

By contrast, “in neurology, we ask: ‘Where is the lesion?’ Studying brain networks could potentially help us diagnose and treat people with psychiatric illness more effectively, just as we treat neurological disorders,” he added.

The findings were published online in Nature Human Behavior.
 

Beyond symptom checklists

Dr. Taylor noted that, in the field of psychiatry, “we often study disorders in isolation,” such as generalized anxiety disorder and major depressive disorder.

“But what see clinically is that half of patients meet the criteria for more than one psychiatric disorder,” he said. “It can be difficult to diagnose and treat these patients, and there are worse treatment outcomes.”

There is also a “discrepancy” between how these disorders are studied (one at a time) and how patients are treated in clinic, Dr. Taylor noted. And there is increasing evidence that psychiatric disorders may share a common neurobiology.

This “highlights the possibility of potentially developing transdiagnostic treatments based on common neurobiology, not just symptom checklists,” Dr. Taylor said.

Prior work “has attempted to map abnormalities to common brain regions rather than to a common brain network,” the investigators wrote. Moreover, “prior studies have rarely tested specificity by comparing psychiatric disorders to other brain disorders.”

In the current study, the researchers used “morphometric brain lesion datasets coupled with a wiring diagram of the human brain to derive a convergent brain network for psychiatric illness.”

They analyzed four large published datasets. Dataset 1 was sourced from an activation likelihood estimation meta-analysis (ALE) of whole-brain voxel-based studies that compared patients with psychiatric disorders such as schizophrenia, BD, depression, addiction, OCD, and anxiety to healthy controls (n = 193 studies; 15,892 individuals in total).

Dataset 2 was drawn from published neuroimaging studies involving patients with Alzheimer’s disease (AD) and other neurodegenerative conditions (n = 72 studies). They reported coordinates regarding which patients with these disorders had more atrophy compared with control persons.

Dataset 3 was sourced from the Vietnam Head Injury study, which followed veterans with and those without penetrating head injuries (n = 194 veterans with injuries). Dataset 4 was sourced from published neurosurgical ablation coordinates for depression.
 

Shared neurobiology

Upon analyzing dataset 1, the researchers found decreased gray matter in the bilateral anterior insula, dorsal anterior cingulate cortex, dorsomedial prefrontal cortex, thalamus, amygdala, hippocampus, and parietal operculum – findings that are “consistent with prior work.”

However, fewer than 35% of the studies contributed to any single cluster; and no cluster was specific to psychiatric versus neurodegenerative coordinates (drawn from dataset 2).

On the other hand, coordinate network mapping yielded “more statistically robust” (P < .001) results, which were found in 85% of the studies. “Psychiatric atrophy coordinates were functionally connected to the same network of brain regions,” the researchers reported.

This network was defined by two types of connectivity, positive and negative.

“The topography of this transdiagnostic network was independent of the statistical threshold and specific to psychiatric (vs. neurodegenerative) disorders, with the strongest peak occurring in the posterior parietal cortex (Brodmann Area 7) near the intraparietal sulcus,” the investigators wrote.

When lesions from dataset 3 were overlaid onto the ALE map and the transdiagnostic network in order to evaluate whether damage to either map correlated with number of post-lesion psychiatric diagnosis, results showed no evidence of a correlation between psychiatric comorbidity and damage on the ALE map (Pearson r, 0.02; P = .766).

However, when the same approach was applied to the transdiagnostic network, a statistically significant correlation was found between psychiatric comorbidity and lesion damage (Pearson r, –0.21; P = .01). A multiple regression model showed that the transdiagnostic, but not the ALE, network “independently predicted the number of post-lesion psychiatric diagnoses” (P = .003 vs. P = .1), the investigators reported.

All four neurosurgical ablative targets for psychiatric disorders found on analysis of dataset 4 “intersected” and aligned with the transdiagnostic network.

“The study does not immediately impact clinical practice, but it would be helpful for practicing clinicians to know that psychiatric disorders commonly co-occur and might share common neurobiology and a convergent brain network,” Dr. Taylor said.

“Future work based on our findings could potentially influence clinical trials and clinical practice, especially in the area of brain stimulation,” he added.
 

‘Exciting new targets’

In a comment, Desmond Oathes, PhD, associate director, Center for Neuromodulation and Stress, University of Pennsylvania, Philadelphia, said the “next step in the science is to combine individual brain imaging, aka, ‘individualized connectomes,’ with these promising group maps to determine something meaningful at the individual patient level.”

Dr. Oathes, who is also a faculty clinician at the Center for the Treatment and Study of Anxiety and was not involved with the study, noted that an open question is whether the brain volume abnormalities/atrophy “can be changed with treatment and in what direction.”

A “strong take-home message from this paper is that brain volume measures from single coordinates are noisy as measures of psychiatric abnormality, whereas network effects seem to be especially sensitive for capturing these effects,” Dr. Oathes said.

The “abnormal networks across these disorders do not fit easily into well-known networks from healthy participants. However, they map well onto other databases relevant to psychiatric disorders and offer exciting new potential targets for prospective treatment studies,” he added.

The investigators received no specific funding for this work. Dr. Taylor reported no relevant financial relationships. Dr. Oathes reported no relevant financial relationships.

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

Adhering to six healthy lifestyle behaviors is linked to slower memory decline in older adults, a large population-based study suggests.

Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.

After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.

“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.

“This study might offer important information to protect older adults against memory decline,” they add.

The study was published online in the BMJ.
 

Preventing memory decline

Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.

Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”

Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.

To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.

The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.

Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.

The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.

“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).

Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.

Important for public health

During the 10-year period, 7,164 participants died, and 3,567 stopped participating.

Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.

Healthy diet had the strongest protective effect on memory.

‘Important, encouraging’ research

In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”

However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”

Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”

In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.

They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.

The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.

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

Adhering to six healthy lifestyle behaviors is linked to slower memory decline in older adults, a large population-based study suggests.

Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.

After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.

“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.

“This study might offer important information to protect older adults against memory decline,” they add.

The study was published online in the BMJ.
 

Preventing memory decline

Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.

Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”

Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.

To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.

The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.

Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.

The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.

“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).

Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.

Important for public health

During the 10-year period, 7,164 participants died, and 3,567 stopped participating.

Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.

Healthy diet had the strongest protective effect on memory.

‘Important, encouraging’ research

In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”

However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”

Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”

In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.

They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.

The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.

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

Adhering to six healthy lifestyle behaviors is linked to slower memory decline in older adults, a large population-based study suggests.

Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.

After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.

“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.

“This study might offer important information to protect older adults against memory decline,” they add.

The study was published online in the BMJ.
 

Preventing memory decline

Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.

Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”

Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.

To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.

The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.

Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.

The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.

“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).

Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.

Important for public health

During the 10-year period, 7,164 participants died, and 3,567 stopped participating.

Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.

Healthy diet had the strongest protective effect on memory.

‘Important, encouraging’ research

In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”

However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”

Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”

In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.

They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.

The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.

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

THE CASE

James B* is a 7-year-old Black child who presented to his primary care physician (PCP) for a well-child visit. During preventive health screening, James’ mother expressed concerns about his behavior, characterizing him as immature, aggressive, destructive, and occasionally self-loathing. She described him as physically uncoordinated, struggling to keep up with his peers in sports, and tiring after 20 minutes of activity. James slept 10 hours nightly but was often restless and snored intermittently. As a second grader, his academic achievement was not progressing, and he had become increasingly inattentive at home and at school. James’ mother offered several examples of his fighting with his siblings, noncompliance with morning routines, and avoidance of learning activities. Additionally, his mother expressed concern that James, as a Black child, might eventually be unfairly labeled as a problem child by his teachers or held back a grade level in school.

Although James did not have a family history of developmental delays or learning disorders, he had not met any milestones on time for gross or fine motor, language, cognitive, and social-emotional skills. James had a history of chronic otitis media, for which pressure equalizer tubes were inserted at age 2 years. He had not had any major physical injuries, psychological trauma, recent life transitions, or adverse childhood events. When asked, James’ mother acknowledged symptoms of maternal depression but alluded to faith-based reasons for not seeking treatment for herself.

James’ physical examination was unremarkable. His height, weight, and vitals were all within normal limits. However, he had some difficulty with verbal articulation and expression and showed signs of a possible vocal tic. Based on James’ presentation, his PCP suspected attention-deficit/hyperactivity disorder (ADHD), as well as neurodevelopmental delays.

The PCP gave James’ mother the Strengths and Difficulties Questionnaire to complete and the Vanderbilt Assessment Scales for her and James’ teacher to fill out independently and return to the clinic. The PCP also instructed James’ mother on how to use a sleep diary to maintain a 1-month log of his sleep patterns and habits. The PCP consulted the integrated behavioral health clinician (IBHC; a clinical social worker embedded in the primary care clinic) and made a warm handoff for the IBHC to further assess James’ maladaptive behaviors and interactions.

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

James is one of more than 6 million children, ages 3 to 17 years, in the United States who live with ADHD.^1,2 ADHD is the most common neurodevelopmental disorder among children, and it affects multiple cognitive and behavioral domains throughout the lifespan.³ Children with ADHD often initially present in primary care settings; thus, PCPs are well positioned to diagnose the disorder and provide longitudinal treatment. This Behavioral Health Consult reviews clinical assessment and practice guidelines, as well as treatment recommendations applicable across different areas of influence—individual, family, community, and systems—for PCPs and IBHCs to use in managing ADHD in children.

ADHD features can vary by age and sex

ADHD is a persistent pattern of inattention or hyperactivity and impulsivity interfering with functioning or development in childhood and functioning later in adulthood. ADHD symptoms manifest prior to age 12 years and must occur in 2 or more settings.⁴ Symptoms should not be better explained by another psychiatric disorder or occur exclusively during the course of another disorder (TABLE 1).⁴

Psychostimulants are preferred for ADHD. However, a variety of medications are available and may prove efficacious as children grow and their symptoms and the capacity to manage them change.

The rate of heritability is high, with significant incidence among first-degree relatives.⁴ Children with ADHD show executive functioning deficits in 1 or more cognitive domains (eg, visuospatial, memory, inhibitions, decision making, and reward regulation).^4,5 The prevalence of ADHD nationally is approximately 9.8% (2.2%, ages 3-5 years; 10%, ages 6-11 years; 13.2%, ages 12-17 years) in children and adolescents; worldwide prevalence is 7.2%.^1,6 It persists among 2.6% to 6.8% of adults worldwide.⁷

Research has shown that boys ages 6 to 11 years are significantly more likely than girls to exhibit attention-getting, externalizing behaviors or conduct problems (eg, hyperactivity, impulsivity, disruption, aggression).^1,6 On the other hand, girls ages 12 to 17 years tend to display internalized (eg, depressed mood, anxiety, low self-esteem) or inattentive behaviors, which clinicians and educators may assess as less severe and warranting fewer supportive measures.¹

The prevalence of ADHD and its associated factors, which evolve through maturation, underscore the importance of persistent, patient-centered, and collaborative PCP and IBHC clinical management.

Continue to: Begin with a screening tool, move to a clinical interview

 

 

Begin with a screening tool, move to a clinical interview

When caregivers express concerns about their child’s behavior, focus, mood, learning, and socialization, consider initiating a multimodal evaluation for ADHD.^5,8 Embarking on an ADHD assessment can require extended or multiple visits to arrive at the diagnosis, followed by still more visits to confirm a course of care and adjust medications. The integrative care approach described in the patient case and elaborated on later in this article can help facilitate assessment and treatment of ADHD.⁹

Signs of ADHD may be observed at initial screening using a tool such as the Ages & Stages Questionnaire (https://agesandstages.com/products-pricing/asq3/) to reveal indications of norm deviations or delays commensurate with ADHD.¹⁰ However, to substantiate the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria for an accurate diagnosis,⁴ the American Academy of Pediatrics (AAP) clinical practice guidelines require a thorough clinical interview, administration of a standardized assessment tool, and review of objective reports in conjunction with a physical examination and psychosocial evaluation.⁶ Standardized meas­ures of psychological, neurocognitive, and academic achievement reported by caregivers and collateral contacts (eg, teachers, counselors, coaches, care providers) are needed to maximize data objectivity and symptom accuracy across settings (TABLE 2^10-17). Additionally, periodic reassessment is recommended to validate changes in diagnostic subtype and treatment plans due to the chronic and dynamic nature of ADHD.

Consider comorbidities and alternate diagnoses

The diagnostic possibility of ADHD should also prompt consideration of other childhood disorders due to the high potential for comorbidities.^4,6 In a 2016 study, approximately 64% of children with ADHD exhibited another developmental or psychiatric disorder at some point. These disorders included oppositional defiant or conduct disorders (52%), anxiety (33%), depression (17%), and autism spectrum disorder (14%), as well as Tourette syndrome, learning or language disorders, motor delays, substance use disorders, sleep-wake disorders, personality disorders, and ­suicidality.¹⁸

Various medical disorders may manifest with similar signs or symptoms to ADHD, such as thyroid disorders, seizure disorders, adverse drug effects, anemia, genetic anomalies, and others.^6,19 Although further research is needed to ascertain potential associations between recurrent otitis media and language delay and later social, cognitive, or attention challenges, early consultation with an otolaryngologist is warranted if such concerns arise in a child’s early years.²⁰ Following the initial assessment, conduct a targeted examination and lab testing to rule out co-occurring conditions or comorbidities.

If there are behavioral concerns or developmental delays associated with tall stature for age or pubertal or testicular development anomalies, consult a geneticist and a developmental pediatrician for targeted testing and neurodevelopmental assessment, respectively. For example, ADHD is a common comorbidity among boys who also have XYY syndrome (Jacobs syndrome). However, due to the variability of symptoms and severity, XYY syndrome often goes undiagnosed, leaving a host of compounding pervasive and developmental problems untreated. Overall, more than two-thirds of patients with ADHD and a co-occurring condition are either inaccurately diagnosed or not referred for additional assessment and adjunct treatment.²¹

Continue to: Risks that arise over time

Risks that arise over time. As ADHD persists, adolescents are at greater risk for psychiatric comorbidities, suicidality, and functional impairments (eg, risky behaviors, occupational problems, truancy, delinquency, and poor self-esteem).^4,8 Adolescents with internalized behaviors are more likely to experience comorbid depressive disorders with increased risk for self-harm.^4,5,8 As adolescents age and their sense of autonomy increases, there is a tendency among those who have received a diagnosis of ADHD to minimize symptoms and decrease the frequency of routine clinic visits along with medication use and treatment compliance.³ Additionally, abuse, misuse, and misappropriation of stimulants among teens and young adults are commonplace.

Wide-scope, multidisciplinary evaluation and close clinical management reduce the potential for imprecise diagnoses, particularly at critical developmental junctures. AAP suggests that PCPs can treat mild and moderate cases of ADHD, but if the treating clinician does not have adequate training, experience, time, or clinical support to manage this condition, early referral is warranted.⁶

A guide to pharmacotherapy

Approximately 77% of children ages 2 to 17 years with a diagnosis of ADHD receive any form of treatment.² Treatment for ADHD can include behavioral therapy and medication.² AAP clinical practice guidelines caution against prescribing medications for children younger than 6 years, relying instead on ­caregiver-, teacher-, or clinician-­administered behavioral strategies and parental training in behavioral modification. For children and adolescents between ages 6 and 18 years, first-line ­treatment includes pharmacotherapy balanced with behavioral therapy, academic modifications, and educational supports (eg, 504 Plan, individualized education plan [IEP]).⁶

Psychostimulants are preferred. These agents (eg, methylphenidate, amphetamine) remain the most efficacious class of medications to reduce hyperactivity and inattentiveness and to improve function. While long-acting psychostimulants are associated with better medication adherence and ­adverse-effect tolerance than are short-acting forms, the latter offer more flexibility in dosing. Start by titrating any stimulant to the lowest effective dose; reassess monthly until potential rebound effects stabilize.

More than twothirds of ADHD patients with a co-occurring condition are either inaccurately diagnosed or not referred for additional assessment and adjunct treatment.

Due to potential adverse effects of this class of medication, screen for any family history or personal risk for structural or electrical cardiac anomalies before starting pharmacotherapy. If any such risks exist, arrange for further cardiac evaluation before initiating medication.⁶ Adverse effects of stimulants include reduced appetite, gastrointestinal symptoms, headaches, anxiousness, parasomnia, tachycardia, and hypertension.

Continue to: Once medication is stabilized...

Once medication is stabilized, monitor treatment 2 to 3 times per year thereafter; watch for longer-term adverse effects such as weight loss, decreased growth rate, and psychiatric comorbidities including the Food and Drug Administration (FDA)’s black box warning of increased risk for suicidality.^5,6,22

Other options. The optimal duration of psychostimulant use remains debatable, as existing evidence does not support its long-term use (10 years) over other interventions, such as nonstimulants and nonmedicinal therapies.²² Although backed by less evidence, additional medications indicated for the treatment of ADHD include: (1) atomoxetine, a selective norepinephrine reuptake inhibitor, and (2) the selective alpha-2 adrenergic agonists, extended-release guanfacine and extended-release clonidine (third-line agent).²²

Adverse effects of these FDA-approved medications are similar to those observed in stimulant medications. Evaluation of cardiac risks is recommended before starting nonstimulant medications. The alpha-2 adrenergic agonists may also be used as adjunct therapies to stimulants. Before stopping an alpha-2 adrenergic agonist, taper the dosage slowly to avoid the risk for rebound hypertension.^6,23 Given the wide variety of medication options and variability of effects, it may be necessary to try different medications as children grow and their symptoms and capacity to manage them change. Additional guidance on FDA-approved medications is available at www.ADHDMedicationGuide.com.

How multilevel care coordination can work

As with other chronic or developmental conditions, the treatment of ADHD requires an interdisciplinary perspective. Continuous, comprehensive case management can help patients overcome obstacles to wellness by balancing the resolution of problems with the development of resilience. Well-documented collaboration of subspecialists, educators, and other stakeholders engaged in ADHD care at multiple levels (individual, family, community, and health care system) increases the likelihood of meaningful, sustainable gains. Using a patient-centered medical home framework, IBHCs or other allied health professionals embedded in, or co-located with, primary care settings can be key to accessing evidence-based treatments that include: psycho-­education and mindfulness-based stress reduction training for caregivers^24,25; occupational,²⁶ cognitive behavioral,²⁷ or family therapies^28,29; neuro-feedback; computer-based attention training; group- or community-based interventions; and academic and social supports.^5,8

Evidence shows that recognition and diagnostic specificity of ADHD and comorbidities— not true prevalence—vary more widely among minority than among nonminority populations.

Treatment approaches that capitalize on children’s neurologic and psychological plasticity and fortify self-efficacy with developmentally appropriate tools empower them to surmount ADHD symptoms over time.²³ Facilitating children’s resilience within a developmental framework and health system’s capacities with socio-culturally relevant approaches, consultation, and research can optimize outcomes and mitigate pervasiveness into adulthood. While the patient is at the center of treatment, it is important to consider the family, school, and communities in which the child lives, learns, and plays. PCPs and IBHCs together can consider a “try and track” method to follow progress, changes, and outcomes over time. With this method, the physician can employ approaches that focus on the patient, caregiver, or the caregiver–child interaction (TABLE 3).

Continue to: Assess patients' needs and the resources available

Assess patients’ needs and the resources available throughout the system of care beyond the primary care setting. Stay abreast of hospital policies, health care insurance coverage, and community- and school-based health programs, and any gaps in adequate and equitable assessment and treatment. For example, while clinical recommendations include psychiatric care, health insurance availability or limits in coverage may dissuade caregivers from seeking help or limit initial or long-term access to resources for help.³⁰ Integrating or advocating for clinic support resources or staffing to assist patients in navigating and mitigating challenges may lessen the management burden and increase the likelihood and longevity of favorable health outcomes.

Steps to ensuring health care equity

Among children of historically marginalized and racial and ethnic minority groups or those of populations affected by health disparities, ADHD symptoms and needs are often masked by structural biases that lead to inequitable care and outcomes, as well as treatment misprioritization or delays.³¹ In particular, evidence has shown that recognition and diagnostic specificity of ADHD and comorbidities, not prevalence, vary more widely among minority than among nonminority populations,³² contributing to the 23% of children with ADHD who receive no treatment at all.²

Understand caregiver concerns. This diagnosis discrepancy is correlated with symptom rating sensitivities (eg, reliability, perception, accuracy) among informants and how caregivers observe, perceive, appreciate, understand, and report behaviors. This discrepancy is also related to cultural belief differences, physician–patient communication variants, and a litany of other socioeconomic determinants.^2,4,31 Caregivers from some cultural, ethnic, or socioeconomic backgrounds may be doubtful of psychiatric assessment, diagnoses, treatment, or medication, and that can impact how children are engaged in clinical and educational settings from the outset.³¹ In the case we described, James’ mother was initially hesitant to explore psychotropic medications and was concerned about stigmatization within the school system. She also seemed to avoid psychiatric treatment for her own depressive symptoms due to cultural and religious beliefs.

Health care provider concerns. Some PCPs may hesitate to explore medications due to limited knowledge and skill in dosing and titrating based on a child’s age, stage, and symptoms, and a perceived lack of competence in managing ADHD. This, too, can indirectly perpetuate existing health disparities. Furthermore, ADHD symptoms may be deemed a secondary or tertiary concern if other complex or urgent medical or undifferentiated developmental problems manifest.

Compounding matters is the limited dissemination of empiric research articles (including randomized controlled trials with representative samples) and limited education on the effectiveness and safety of psychopharmacologic interventions across the lifespan and different cultural and ethnic groups.⁴ Consequently, patients who struggle with unmanaged ADHD symptoms are more likely to have chronic mental health disorders, maladaptive behaviors, and other co-occurring conditions contributing to the complexity of individual needs, health care burdens, or justice system involvement; this is particularly true for those of racial and ethnic minorities.³³

Continue to: Impact of the COVID-19 pandemic

Impact of the COVID-19 pandemic. Patients—particularly those in minority or health disparity populations—who under normal circumstances might have been hesitant to seek help may have felt even more reluctant to do so during the COVID-19 pandemic. We have not yet learned the degree to which limited availability of preventive health care services, decreased routine visits, and fluctuating insurance coverage has impacted the diagnosis, management, or severity of childhood disorders during the past 2 years. Reports of national findings indicate that prolonged periods out of school and reduced daily structure were associated with increased disruptions in mood, sleep, and appetite, particularly among children with pre-existing pathologies. Evidence suggests that school-aged children experienced more anxiety, regressive behaviors, and parasomnias than they did before the pandemic, while adolescents experienced more isolation and depressive symptoms.^34,35

However, there remains a paucity of large-scale or representative studies that use an intersectional lens to examine the influence of COVID-19 on children with ADHD. Therefore, PCPs and IBHCs should refocus attention on possibly undiagnosed, stagnated, or regressed ADHD cases, as well as the adults who care for them. (See “5 ways to overcome Tx barriers and promote health equity.”)

THE CASE

During a follow-up visit 1 month later, the PCP confirmed the clinical impression of ADHD combined presentation with a clinical interview and review of the Strengths and Difficulties Questionnaire completed by James’ mother and the Vanderbilt Assessment Scales completed by James’ mother and teacher. The sleep diary indicated potential problems and apneas worthy of consults for pulmonary function testing, a sleep study, and otolaryngology examination. The PCP informed James’ mother on sleep hygiene strategies and ADHD medication options. She indicated that she wanted to pursue the referrals and behavioral modifications before starting any medication trial.

The PCP referred James to a developmental pediatrician for in-depth assessment of his overall development, learning, and functioning. The developmental pediatrician ultimately confirmed the diagnosis of ADHD, as well as motor and speech delays warranting physical, occupational, and speech therapies. The developmental pediatrician also referred James for targeted genetic testing because she suspected a genetic disorder (eg, XYY syndrome).

The PCP reconnected James and his mother to the IBHC to facilitate subspecialty and school-based care coordination and to provide in-office and home-based interventions. The IBHC assessed James’ emotional dysregulation and impulsivity as adversely impacting his interpersonal relationships and planned to address these issues with behavioral and ­parent–child interaction therapies and skills training during the course of 6 to 12 visits. James’ mother was encouraged to engage his teacher on his academic performance and to initiate a 504 Plan or IEP for in-school accommodations and support. The IBHC aided in tracking his assessments, referrals, follow-ups, access barriers, and treatment goals.

After 6 months, James had made only modest progress, and his mother requested that he begin a trial of medication. Based on his weight, symptoms, behavior patterns, and sleep habits, the PCP prescribed ­extended-release dexmethylphenidate 10 mg each morning, then extended-release clonidine 0.1 mg nightly. With team-based clinical management of pharmacologic, behavioral, physical, speech, and occupational therapies, James’ behavior and sleep improved, and the signs of a vocal tic diminished.

By the next school year, James demonstrated a marked improvement in impulse control, attention, and academic functioning. He followed up with the PCP at least quarterly for reassessment of his symptoms, growth, and experience of adverse effects, and to titrate medications accordingly. James and his mother continued to work closely with the IBHC monthly to engage interventions and to monitor his progress at home and school.

CORRESPONDENCE
Sundania J. W. Wonnum, PhD, LCSW, National Institute on Minority Health and Health Disparities, 6707 Democracy Boulevard, Suite 800, Bethesda, MD 20892; sundania.wonnum@nih.gov

THE CASE

James B* is a 7-year-old Black child who presented to his primary care physician (PCP) for a well-child visit. During preventive health screening, James’ mother expressed concerns about his behavior, characterizing him as immature, aggressive, destructive, and occasionally self-loathing. She described him as physically uncoordinated, struggling to keep up with his peers in sports, and tiring after 20 minutes of activity. James slept 10 hours nightly but was often restless and snored intermittently. As a second grader, his academic achievement was not progressing, and he had become increasingly inattentive at home and at school. James’ mother offered several examples of his fighting with his siblings, noncompliance with morning routines, and avoidance of learning activities. Additionally, his mother expressed concern that James, as a Black child, might eventually be unfairly labeled as a problem child by his teachers or held back a grade level in school.

Although James did not have a family history of developmental delays or learning disorders, he had not met any milestones on time for gross or fine motor, language, cognitive, and social-emotional skills. James had a history of chronic otitis media, for which pressure equalizer tubes were inserted at age 2 years. He had not had any major physical injuries, psychological trauma, recent life transitions, or adverse childhood events. When asked, James’ mother acknowledged symptoms of maternal depression but alluded to faith-based reasons for not seeking treatment for herself.

James’ physical examination was unremarkable. His height, weight, and vitals were all within normal limits. However, he had some difficulty with verbal articulation and expression and showed signs of a possible vocal tic. Based on James’ presentation, his PCP suspected attention-deficit/hyperactivity disorder (ADHD), as well as neurodevelopmental delays.

The PCP gave James’ mother the Strengths and Difficulties Questionnaire to complete and the Vanderbilt Assessment Scales for her and James’ teacher to fill out independently and return to the clinic. The PCP also instructed James’ mother on how to use a sleep diary to maintain a 1-month log of his sleep patterns and habits. The PCP consulted the integrated behavioral health clinician (IBHC; a clinical social worker embedded in the primary care clinic) and made a warm handoff for the IBHC to further assess James’ maladaptive behaviors and interactions.

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

James is one of more than 6 million children, ages 3 to 17 years, in the United States who live with ADHD.^1,2 ADHD is the most common neurodevelopmental disorder among children, and it affects multiple cognitive and behavioral domains throughout the lifespan.³ Children with ADHD often initially present in primary care settings; thus, PCPs are well positioned to diagnose the disorder and provide longitudinal treatment. This Behavioral Health Consult reviews clinical assessment and practice guidelines, as well as treatment recommendations applicable across different areas of influence—individual, family, community, and systems—for PCPs and IBHCs to use in managing ADHD in children.

ADHD features can vary by age and sex

ADHD is a persistent pattern of inattention or hyperactivity and impulsivity interfering with functioning or development in childhood and functioning later in adulthood. ADHD symptoms manifest prior to age 12 years and must occur in 2 or more settings.⁴ Symptoms should not be better explained by another psychiatric disorder or occur exclusively during the course of another disorder (TABLE 1).⁴

Psychostimulants are preferred for ADHD. However, a variety of medications are available and may prove efficacious as children grow and their symptoms and the capacity to manage them change.

The rate of heritability is high, with significant incidence among first-degree relatives.⁴ Children with ADHD show executive functioning deficits in 1 or more cognitive domains (eg, visuospatial, memory, inhibitions, decision making, and reward regulation).^4,5 The prevalence of ADHD nationally is approximately 9.8% (2.2%, ages 3-5 years; 10%, ages 6-11 years; 13.2%, ages 12-17 years) in children and adolescents; worldwide prevalence is 7.2%.^1,6 It persists among 2.6% to 6.8% of adults worldwide.⁷

Research has shown that boys ages 6 to 11 years are significantly more likely than girls to exhibit attention-getting, externalizing behaviors or conduct problems (eg, hyperactivity, impulsivity, disruption, aggression).^1,6 On the other hand, girls ages 12 to 17 years tend to display internalized (eg, depressed mood, anxiety, low self-esteem) or inattentive behaviors, which clinicians and educators may assess as less severe and warranting fewer supportive measures.¹

The prevalence of ADHD and its associated factors, which evolve through maturation, underscore the importance of persistent, patient-centered, and collaborative PCP and IBHC clinical management.

Continue to: Begin with a screening tool, move to a clinical interview

 

 

Begin with a screening tool, move to a clinical interview

When caregivers express concerns about their child’s behavior, focus, mood, learning, and socialization, consider initiating a multimodal evaluation for ADHD.^5,8 Embarking on an ADHD assessment can require extended or multiple visits to arrive at the diagnosis, followed by still more visits to confirm a course of care and adjust medications. The integrative care approach described in the patient case and elaborated on later in this article can help facilitate assessment and treatment of ADHD.⁹

Signs of ADHD may be observed at initial screening using a tool such as the Ages & Stages Questionnaire (https://agesandstages.com/products-pricing/asq3/) to reveal indications of norm deviations or delays commensurate with ADHD.¹⁰ However, to substantiate the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria for an accurate diagnosis,⁴ the American Academy of Pediatrics (AAP) clinical practice guidelines require a thorough clinical interview, administration of a standardized assessment tool, and review of objective reports in conjunction with a physical examination and psychosocial evaluation.⁶ Standardized meas­ures of psychological, neurocognitive, and academic achievement reported by caregivers and collateral contacts (eg, teachers, counselors, coaches, care providers) are needed to maximize data objectivity and symptom accuracy across settings (TABLE 2^10-17). Additionally, periodic reassessment is recommended to validate changes in diagnostic subtype and treatment plans due to the chronic and dynamic nature of ADHD.

Consider comorbidities and alternate diagnoses

The diagnostic possibility of ADHD should also prompt consideration of other childhood disorders due to the high potential for comorbidities.^4,6 In a 2016 study, approximately 64% of children with ADHD exhibited another developmental or psychiatric disorder at some point. These disorders included oppositional defiant or conduct disorders (52%), anxiety (33%), depression (17%), and autism spectrum disorder (14%), as well as Tourette syndrome, learning or language disorders, motor delays, substance use disorders, sleep-wake disorders, personality disorders, and ­suicidality.¹⁸

Various medical disorders may manifest with similar signs or symptoms to ADHD, such as thyroid disorders, seizure disorders, adverse drug effects, anemia, genetic anomalies, and others.^6,19 Although further research is needed to ascertain potential associations between recurrent otitis media and language delay and later social, cognitive, or attention challenges, early consultation with an otolaryngologist is warranted if such concerns arise in a child’s early years.²⁰ Following the initial assessment, conduct a targeted examination and lab testing to rule out co-occurring conditions or comorbidities.

If there are behavioral concerns or developmental delays associated with tall stature for age or pubertal or testicular development anomalies, consult a geneticist and a developmental pediatrician for targeted testing and neurodevelopmental assessment, respectively. For example, ADHD is a common comorbidity among boys who also have XYY syndrome (Jacobs syndrome). However, due to the variability of symptoms and severity, XYY syndrome often goes undiagnosed, leaving a host of compounding pervasive and developmental problems untreated. Overall, more than two-thirds of patients with ADHD and a co-occurring condition are either inaccurately diagnosed or not referred for additional assessment and adjunct treatment.²¹

Continue to: Risks that arise over time

Risks that arise over time. As ADHD persists, adolescents are at greater risk for psychiatric comorbidities, suicidality, and functional impairments (eg, risky behaviors, occupational problems, truancy, delinquency, and poor self-esteem).^4,8 Adolescents with internalized behaviors are more likely to experience comorbid depressive disorders with increased risk for self-harm.^4,5,8 As adolescents age and their sense of autonomy increases, there is a tendency among those who have received a diagnosis of ADHD to minimize symptoms and decrease the frequency of routine clinic visits along with medication use and treatment compliance.³ Additionally, abuse, misuse, and misappropriation of stimulants among teens and young adults are commonplace.

Wide-scope, multidisciplinary evaluation and close clinical management reduce the potential for imprecise diagnoses, particularly at critical developmental junctures. AAP suggests that PCPs can treat mild and moderate cases of ADHD, but if the treating clinician does not have adequate training, experience, time, or clinical support to manage this condition, early referral is warranted.⁶

A guide to pharmacotherapy

Approximately 77% of children ages 2 to 17 years with a diagnosis of ADHD receive any form of treatment.² Treatment for ADHD can include behavioral therapy and medication.² AAP clinical practice guidelines caution against prescribing medications for children younger than 6 years, relying instead on ­caregiver-, teacher-, or clinician-­administered behavioral strategies and parental training in behavioral modification. For children and adolescents between ages 6 and 18 years, first-line ­treatment includes pharmacotherapy balanced with behavioral therapy, academic modifications, and educational supports (eg, 504 Plan, individualized education plan [IEP]).⁶

Psychostimulants are preferred. These agents (eg, methylphenidate, amphetamine) remain the most efficacious class of medications to reduce hyperactivity and inattentiveness and to improve function. While long-acting psychostimulants are associated with better medication adherence and ­adverse-effect tolerance than are short-acting forms, the latter offer more flexibility in dosing. Start by titrating any stimulant to the lowest effective dose; reassess monthly until potential rebound effects stabilize.

More than twothirds of ADHD patients with a co-occurring condition are either inaccurately diagnosed or not referred for additional assessment and adjunct treatment.

Due to potential adverse effects of this class of medication, screen for any family history or personal risk for structural or electrical cardiac anomalies before starting pharmacotherapy. If any such risks exist, arrange for further cardiac evaluation before initiating medication.⁶ Adverse effects of stimulants include reduced appetite, gastrointestinal symptoms, headaches, anxiousness, parasomnia, tachycardia, and hypertension.

Continue to: Once medication is stabilized...

Once medication is stabilized, monitor treatment 2 to 3 times per year thereafter; watch for longer-term adverse effects such as weight loss, decreased growth rate, and psychiatric comorbidities including the Food and Drug Administration (FDA)’s black box warning of increased risk for suicidality.^5,6,22

Other options. The optimal duration of psychostimulant use remains debatable, as existing evidence does not support its long-term use (10 years) over other interventions, such as nonstimulants and nonmedicinal therapies.²² Although backed by less evidence, additional medications indicated for the treatment of ADHD include: (1) atomoxetine, a selective norepinephrine reuptake inhibitor, and (2) the selective alpha-2 adrenergic agonists, extended-release guanfacine and extended-release clonidine (third-line agent).²²

Adverse effects of these FDA-approved medications are similar to those observed in stimulant medications. Evaluation of cardiac risks is recommended before starting nonstimulant medications. The alpha-2 adrenergic agonists may also be used as adjunct therapies to stimulants. Before stopping an alpha-2 adrenergic agonist, taper the dosage slowly to avoid the risk for rebound hypertension.^6,23 Given the wide variety of medication options and variability of effects, it may be necessary to try different medications as children grow and their symptoms and capacity to manage them change. Additional guidance on FDA-approved medications is available at www.ADHDMedicationGuide.com.

How multilevel care coordination can work

As with other chronic or developmental conditions, the treatment of ADHD requires an interdisciplinary perspective. Continuous, comprehensive case management can help patients overcome obstacles to wellness by balancing the resolution of problems with the development of resilience. Well-documented collaboration of subspecialists, educators, and other stakeholders engaged in ADHD care at multiple levels (individual, family, community, and health care system) increases the likelihood of meaningful, sustainable gains. Using a patient-centered medical home framework, IBHCs or other allied health professionals embedded in, or co-located with, primary care settings can be key to accessing evidence-based treatments that include: psycho-­education and mindfulness-based stress reduction training for caregivers^24,25; occupational,²⁶ cognitive behavioral,²⁷ or family therapies^28,29; neuro-feedback; computer-based attention training; group- or community-based interventions; and academic and social supports.^5,8

Evidence shows that recognition and diagnostic specificity of ADHD and comorbidities— not true prevalence—vary more widely among minority than among nonminority populations.

Treatment approaches that capitalize on children’s neurologic and psychological plasticity and fortify self-efficacy with developmentally appropriate tools empower them to surmount ADHD symptoms over time.²³ Facilitating children’s resilience within a developmental framework and health system’s capacities with socio-culturally relevant approaches, consultation, and research can optimize outcomes and mitigate pervasiveness into adulthood. While the patient is at the center of treatment, it is important to consider the family, school, and communities in which the child lives, learns, and plays. PCPs and IBHCs together can consider a “try and track” method to follow progress, changes, and outcomes over time. With this method, the physician can employ approaches that focus on the patient, caregiver, or the caregiver–child interaction (TABLE 3).

Continue to: Assess patients' needs and the resources available

Assess patients’ needs and the resources available throughout the system of care beyond the primary care setting. Stay abreast of hospital policies, health care insurance coverage, and community- and school-based health programs, and any gaps in adequate and equitable assessment and treatment. For example, while clinical recommendations include psychiatric care, health insurance availability or limits in coverage may dissuade caregivers from seeking help or limit initial or long-term access to resources for help.³⁰ Integrating or advocating for clinic support resources or staffing to assist patients in navigating and mitigating challenges may lessen the management burden and increase the likelihood and longevity of favorable health outcomes.

Steps to ensuring health care equity

Among children of historically marginalized and racial and ethnic minority groups or those of populations affected by health disparities, ADHD symptoms and needs are often masked by structural biases that lead to inequitable care and outcomes, as well as treatment misprioritization or delays.³¹ In particular, evidence has shown that recognition and diagnostic specificity of ADHD and comorbidities, not prevalence, vary more widely among minority than among nonminority populations,³² contributing to the 23% of children with ADHD who receive no treatment at all.²

Understand caregiver concerns. This diagnosis discrepancy is correlated with symptom rating sensitivities (eg, reliability, perception, accuracy) among informants and how caregivers observe, perceive, appreciate, understand, and report behaviors. This discrepancy is also related to cultural belief differences, physician–patient communication variants, and a litany of other socioeconomic determinants.^2,4,31 Caregivers from some cultural, ethnic, or socioeconomic backgrounds may be doubtful of psychiatric assessment, diagnoses, treatment, or medication, and that can impact how children are engaged in clinical and educational settings from the outset.³¹ In the case we described, James’ mother was initially hesitant to explore psychotropic medications and was concerned about stigmatization within the school system. She also seemed to avoid psychiatric treatment for her own depressive symptoms due to cultural and religious beliefs.

Health care provider concerns. Some PCPs may hesitate to explore medications due to limited knowledge and skill in dosing and titrating based on a child’s age, stage, and symptoms, and a perceived lack of competence in managing ADHD. This, too, can indirectly perpetuate existing health disparities. Furthermore, ADHD symptoms may be deemed a secondary or tertiary concern if other complex or urgent medical or undifferentiated developmental problems manifest.

Compounding matters is the limited dissemination of empiric research articles (including randomized controlled trials with representative samples) and limited education on the effectiveness and safety of psychopharmacologic interventions across the lifespan and different cultural and ethnic groups.⁴ Consequently, patients who struggle with unmanaged ADHD symptoms are more likely to have chronic mental health disorders, maladaptive behaviors, and other co-occurring conditions contributing to the complexity of individual needs, health care burdens, or justice system involvement; this is particularly true for those of racial and ethnic minorities.³³

Continue to: Impact of the COVID-19 pandemic

Impact of the COVID-19 pandemic. Patients—particularly those in minority or health disparity populations—who under normal circumstances might have been hesitant to seek help may have felt even more reluctant to do so during the COVID-19 pandemic. We have not yet learned the degree to which limited availability of preventive health care services, decreased routine visits, and fluctuating insurance coverage has impacted the diagnosis, management, or severity of childhood disorders during the past 2 years. Reports of national findings indicate that prolonged periods out of school and reduced daily structure were associated with increased disruptions in mood, sleep, and appetite, particularly among children with pre-existing pathologies. Evidence suggests that school-aged children experienced more anxiety, regressive behaviors, and parasomnias than they did before the pandemic, while adolescents experienced more isolation and depressive symptoms.^34,35

However, there remains a paucity of large-scale or representative studies that use an intersectional lens to examine the influence of COVID-19 on children with ADHD. Therefore, PCPs and IBHCs should refocus attention on possibly undiagnosed, stagnated, or regressed ADHD cases, as well as the adults who care for them. (See “5 ways to overcome Tx barriers and promote health equity.”)

THE CASE

During a follow-up visit 1 month later, the PCP confirmed the clinical impression of ADHD combined presentation with a clinical interview and review of the Strengths and Difficulties Questionnaire completed by James’ mother and the Vanderbilt Assessment Scales completed by James’ mother and teacher. The sleep diary indicated potential problems and apneas worthy of consults for pulmonary function testing, a sleep study, and otolaryngology examination. The PCP informed James’ mother on sleep hygiene strategies and ADHD medication options. She indicated that she wanted to pursue the referrals and behavioral modifications before starting any medication trial.

The PCP referred James to a developmental pediatrician for in-depth assessment of his overall development, learning, and functioning. The developmental pediatrician ultimately confirmed the diagnosis of ADHD, as well as motor and speech delays warranting physical, occupational, and speech therapies. The developmental pediatrician also referred James for targeted genetic testing because she suspected a genetic disorder (eg, XYY syndrome).

The PCP reconnected James and his mother to the IBHC to facilitate subspecialty and school-based care coordination and to provide in-office and home-based interventions. The IBHC assessed James’ emotional dysregulation and impulsivity as adversely impacting his interpersonal relationships and planned to address these issues with behavioral and ­parent–child interaction therapies and skills training during the course of 6 to 12 visits. James’ mother was encouraged to engage his teacher on his academic performance and to initiate a 504 Plan or IEP for in-school accommodations and support. The IBHC aided in tracking his assessments, referrals, follow-ups, access barriers, and treatment goals.

After 6 months, James had made only modest progress, and his mother requested that he begin a trial of medication. Based on his weight, symptoms, behavior patterns, and sleep habits, the PCP prescribed ­extended-release dexmethylphenidate 10 mg each morning, then extended-release clonidine 0.1 mg nightly. With team-based clinical management of pharmacologic, behavioral, physical, speech, and occupational therapies, James’ behavior and sleep improved, and the signs of a vocal tic diminished.

By the next school year, James demonstrated a marked improvement in impulse control, attention, and academic functioning. He followed up with the PCP at least quarterly for reassessment of his symptoms, growth, and experience of adverse effects, and to titrate medications accordingly. James and his mother continued to work closely with the IBHC monthly to engage interventions and to monitor his progress at home and school.

CORRESPONDENCE
Sundania J. W. Wonnum, PhD, LCSW, National Institute on Minority Health and Health Disparities, 6707 Democracy Boulevard, Suite 800, Bethesda, MD 20892; sundania.wonnum@nih.gov

THE CASE

James B* is a 7-year-old Black child who presented to his primary care physician (PCP) for a well-child visit. During preventive health screening, James’ mother expressed concerns about his behavior, characterizing him as immature, aggressive, destructive, and occasionally self-loathing. She described him as physically uncoordinated, struggling to keep up with his peers in sports, and tiring after 20 minutes of activity. James slept 10 hours nightly but was often restless and snored intermittently. As a second grader, his academic achievement was not progressing, and he had become increasingly inattentive at home and at school. James’ mother offered several examples of his fighting with his siblings, noncompliance with morning routines, and avoidance of learning activities. Additionally, his mother expressed concern that James, as a Black child, might eventually be unfairly labeled as a problem child by his teachers or held back a grade level in school.

Although James did not have a family history of developmental delays or learning disorders, he had not met any milestones on time for gross or fine motor, language, cognitive, and social-emotional skills. James had a history of chronic otitis media, for which pressure equalizer tubes were inserted at age 2 years. He had not had any major physical injuries, psychological trauma, recent life transitions, or adverse childhood events. When asked, James’ mother acknowledged symptoms of maternal depression but alluded to faith-based reasons for not seeking treatment for herself.

James’ physical examination was unremarkable. His height, weight, and vitals were all within normal limits. However, he had some difficulty with verbal articulation and expression and showed signs of a possible vocal tic. Based on James’ presentation, his PCP suspected attention-deficit/hyperactivity disorder (ADHD), as well as neurodevelopmental delays.

The PCP gave James’ mother the Strengths and Difficulties Questionnaire to complete and the Vanderbilt Assessment Scales for her and James’ teacher to fill out independently and return to the clinic. The PCP also instructed James’ mother on how to use a sleep diary to maintain a 1-month log of his sleep patterns and habits. The PCP consulted the integrated behavioral health clinician (IBHC; a clinical social worker embedded in the primary care clinic) and made a warm handoff for the IBHC to further assess James’ maladaptive behaviors and interactions.

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

James is one of more than 6 million children, ages 3 to 17 years, in the United States who live with ADHD.^1,2 ADHD is the most common neurodevelopmental disorder among children, and it affects multiple cognitive and behavioral domains throughout the lifespan.³ Children with ADHD often initially present in primary care settings; thus, PCPs are well positioned to diagnose the disorder and provide longitudinal treatment. This Behavioral Health Consult reviews clinical assessment and practice guidelines, as well as treatment recommendations applicable across different areas of influence—individual, family, community, and systems—for PCPs and IBHCs to use in managing ADHD in children.

ADHD features can vary by age and sex

ADHD is a persistent pattern of inattention or hyperactivity and impulsivity interfering with functioning or development in childhood and functioning later in adulthood. ADHD symptoms manifest prior to age 12 years and must occur in 2 or more settings.⁴ Symptoms should not be better explained by another psychiatric disorder or occur exclusively during the course of another disorder (TABLE 1).⁴

Psychostimulants are preferred for ADHD. However, a variety of medications are available and may prove efficacious as children grow and their symptoms and the capacity to manage them change.

The rate of heritability is high, with significant incidence among first-degree relatives.⁴ Children with ADHD show executive functioning deficits in 1 or more cognitive domains (eg, visuospatial, memory, inhibitions, decision making, and reward regulation).^4,5 The prevalence of ADHD nationally is approximately 9.8% (2.2%, ages 3-5 years; 10%, ages 6-11 years; 13.2%, ages 12-17 years) in children and adolescents; worldwide prevalence is 7.2%.^1,6 It persists among 2.6% to 6.8% of adults worldwide.⁷

Research has shown that boys ages 6 to 11 years are significantly more likely than girls to exhibit attention-getting, externalizing behaviors or conduct problems (eg, hyperactivity, impulsivity, disruption, aggression).^1,6 On the other hand, girls ages 12 to 17 years tend to display internalized (eg, depressed mood, anxiety, low self-esteem) or inattentive behaviors, which clinicians and educators may assess as less severe and warranting fewer supportive measures.¹

The prevalence of ADHD and its associated factors, which evolve through maturation, underscore the importance of persistent, patient-centered, and collaborative PCP and IBHC clinical management.

Continue to: Begin with a screening tool, move to a clinical interview

 

 

Begin with a screening tool, move to a clinical interview

When caregivers express concerns about their child’s behavior, focus, mood, learning, and socialization, consider initiating a multimodal evaluation for ADHD.^5,8 Embarking on an ADHD assessment can require extended or multiple visits to arrive at the diagnosis, followed by still more visits to confirm a course of care and adjust medications. The integrative care approach described in the patient case and elaborated on later in this article can help facilitate assessment and treatment of ADHD.⁹

Signs of ADHD may be observed at initial screening using a tool such as the Ages & Stages Questionnaire (https://agesandstages.com/products-pricing/asq3/) to reveal indications of norm deviations or delays commensurate with ADHD.¹⁰ However, to substantiate the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria for an accurate diagnosis,⁴ the American Academy of Pediatrics (AAP) clinical practice guidelines require a thorough clinical interview, administration of a standardized assessment tool, and review of objective reports in conjunction with a physical examination and psychosocial evaluation.⁶ Standardized meas­ures of psychological, neurocognitive, and academic achievement reported by caregivers and collateral contacts (eg, teachers, counselors, coaches, care providers) are needed to maximize data objectivity and symptom accuracy across settings (TABLE 2^10-17). Additionally, periodic reassessment is recommended to validate changes in diagnostic subtype and treatment plans due to the chronic and dynamic nature of ADHD.

Consider comorbidities and alternate diagnoses

The diagnostic possibility of ADHD should also prompt consideration of other childhood disorders due to the high potential for comorbidities.^4,6 In a 2016 study, approximately 64% of children with ADHD exhibited another developmental or psychiatric disorder at some point. These disorders included oppositional defiant or conduct disorders (52%), anxiety (33%), depression (17%), and autism spectrum disorder (14%), as well as Tourette syndrome, learning or language disorders, motor delays, substance use disorders, sleep-wake disorders, personality disorders, and ­suicidality.¹⁸

Various medical disorders may manifest with similar signs or symptoms to ADHD, such as thyroid disorders, seizure disorders, adverse drug effects, anemia, genetic anomalies, and others.^6,19 Although further research is needed to ascertain potential associations between recurrent otitis media and language delay and later social, cognitive, or attention challenges, early consultation with an otolaryngologist is warranted if such concerns arise in a child’s early years.²⁰ Following the initial assessment, conduct a targeted examination and lab testing to rule out co-occurring conditions or comorbidities.

If there are behavioral concerns or developmental delays associated with tall stature for age or pubertal or testicular development anomalies, consult a geneticist and a developmental pediatrician for targeted testing and neurodevelopmental assessment, respectively. For example, ADHD is a common comorbidity among boys who also have XYY syndrome (Jacobs syndrome). However, due to the variability of symptoms and severity, XYY syndrome often goes undiagnosed, leaving a host of compounding pervasive and developmental problems untreated. Overall, more than two-thirds of patients with ADHD and a co-occurring condition are either inaccurately diagnosed or not referred for additional assessment and adjunct treatment.²¹

Continue to: Risks that arise over time

Risks that arise over time. As ADHD persists, adolescents are at greater risk for psychiatric comorbidities, suicidality, and functional impairments (eg, risky behaviors, occupational problems, truancy, delinquency, and poor self-esteem).^4,8 Adolescents with internalized behaviors are more likely to experience comorbid depressive disorders with increased risk for self-harm.^4,5,8 As adolescents age and their sense of autonomy increases, there is a tendency among those who have received a diagnosis of ADHD to minimize symptoms and decrease the frequency of routine clinic visits along with medication use and treatment compliance.³ Additionally, abuse, misuse, and misappropriation of stimulants among teens and young adults are commonplace.

Wide-scope, multidisciplinary evaluation and close clinical management reduce the potential for imprecise diagnoses, particularly at critical developmental junctures. AAP suggests that PCPs can treat mild and moderate cases of ADHD, but if the treating clinician does not have adequate training, experience, time, or clinical support to manage this condition, early referral is warranted.⁶

A guide to pharmacotherapy

Approximately 77% of children ages 2 to 17 years with a diagnosis of ADHD receive any form of treatment.² Treatment for ADHD can include behavioral therapy and medication.² AAP clinical practice guidelines caution against prescribing medications for children younger than 6 years, relying instead on ­caregiver-, teacher-, or clinician-­administered behavioral strategies and parental training in behavioral modification. For children and adolescents between ages 6 and 18 years, first-line ­treatment includes pharmacotherapy balanced with behavioral therapy, academic modifications, and educational supports (eg, 504 Plan, individualized education plan [IEP]).⁶

Psychostimulants are preferred. These agents (eg, methylphenidate, amphetamine) remain the most efficacious class of medications to reduce hyperactivity and inattentiveness and to improve function. While long-acting psychostimulants are associated with better medication adherence and ­adverse-effect tolerance than are short-acting forms, the latter offer more flexibility in dosing. Start by titrating any stimulant to the lowest effective dose; reassess monthly until potential rebound effects stabilize.

More than twothirds of ADHD patients with a co-occurring condition are either inaccurately diagnosed or not referred for additional assessment and adjunct treatment.

Due to potential adverse effects of this class of medication, screen for any family history or personal risk for structural or electrical cardiac anomalies before starting pharmacotherapy. If any such risks exist, arrange for further cardiac evaluation before initiating medication.⁶ Adverse effects of stimulants include reduced appetite, gastrointestinal symptoms, headaches, anxiousness, parasomnia, tachycardia, and hypertension.

Continue to: Once medication is stabilized...

Once medication is stabilized, monitor treatment 2 to 3 times per year thereafter; watch for longer-term adverse effects such as weight loss, decreased growth rate, and psychiatric comorbidities including the Food and Drug Administration (FDA)’s black box warning of increased risk for suicidality.^5,6,22

Other options. The optimal duration of psychostimulant use remains debatable, as existing evidence does not support its long-term use (10 years) over other interventions, such as nonstimulants and nonmedicinal therapies.²² Although backed by less evidence, additional medications indicated for the treatment of ADHD include: (1) atomoxetine, a selective norepinephrine reuptake inhibitor, and (2) the selective alpha-2 adrenergic agonists, extended-release guanfacine and extended-release clonidine (third-line agent).²²

Adverse effects of these FDA-approved medications are similar to those observed in stimulant medications. Evaluation of cardiac risks is recommended before starting nonstimulant medications. The alpha-2 adrenergic agonists may also be used as adjunct therapies to stimulants. Before stopping an alpha-2 adrenergic agonist, taper the dosage slowly to avoid the risk for rebound hypertension.^6,23 Given the wide variety of medication options and variability of effects, it may be necessary to try different medications as children grow and their symptoms and capacity to manage them change. Additional guidance on FDA-approved medications is available at www.ADHDMedicationGuide.com.

How multilevel care coordination can work

As with other chronic or developmental conditions, the treatment of ADHD requires an interdisciplinary perspective. Continuous, comprehensive case management can help patients overcome obstacles to wellness by balancing the resolution of problems with the development of resilience. Well-documented collaboration of subspecialists, educators, and other stakeholders engaged in ADHD care at multiple levels (individual, family, community, and health care system) increases the likelihood of meaningful, sustainable gains. Using a patient-centered medical home framework, IBHCs or other allied health professionals embedded in, or co-located with, primary care settings can be key to accessing evidence-based treatments that include: psycho-­education and mindfulness-based stress reduction training for caregivers^24,25; occupational,²⁶ cognitive behavioral,²⁷ or family therapies^28,29; neuro-feedback; computer-based attention training; group- or community-based interventions; and academic and social supports.^5,8

Evidence shows that recognition and diagnostic specificity of ADHD and comorbidities— not true prevalence—vary more widely among minority than among nonminority populations.

Treatment approaches that capitalize on children’s neurologic and psychological plasticity and fortify self-efficacy with developmentally appropriate tools empower them to surmount ADHD symptoms over time.²³ Facilitating children’s resilience within a developmental framework and health system’s capacities with socio-culturally relevant approaches, consultation, and research can optimize outcomes and mitigate pervasiveness into adulthood. While the patient is at the center of treatment, it is important to consider the family, school, and communities in which the child lives, learns, and plays. PCPs and IBHCs together can consider a “try and track” method to follow progress, changes, and outcomes over time. With this method, the physician can employ approaches that focus on the patient, caregiver, or the caregiver–child interaction (TABLE 3).

Continue to: Assess patients' needs and the resources available

Assess patients’ needs and the resources available throughout the system of care beyond the primary care setting. Stay abreast of hospital policies, health care insurance coverage, and community- and school-based health programs, and any gaps in adequate and equitable assessment and treatment. For example, while clinical recommendations include psychiatric care, health insurance availability or limits in coverage may dissuade caregivers from seeking help or limit initial or long-term access to resources for help.³⁰ Integrating or advocating for clinic support resources or staffing to assist patients in navigating and mitigating challenges may lessen the management burden and increase the likelihood and longevity of favorable health outcomes.

Steps to ensuring health care equity

Among children of historically marginalized and racial and ethnic minority groups or those of populations affected by health disparities, ADHD symptoms and needs are often masked by structural biases that lead to inequitable care and outcomes, as well as treatment misprioritization or delays.³¹ In particular, evidence has shown that recognition and diagnostic specificity of ADHD and comorbidities, not prevalence, vary more widely among minority than among nonminority populations,³² contributing to the 23% of children with ADHD who receive no treatment at all.²

Understand caregiver concerns. This diagnosis discrepancy is correlated with symptom rating sensitivities (eg, reliability, perception, accuracy) among informants and how caregivers observe, perceive, appreciate, understand, and report behaviors. This discrepancy is also related to cultural belief differences, physician–patient communication variants, and a litany of other socioeconomic determinants.^2,4,31 Caregivers from some cultural, ethnic, or socioeconomic backgrounds may be doubtful of psychiatric assessment, diagnoses, treatment, or medication, and that can impact how children are engaged in clinical and educational settings from the outset.³¹ In the case we described, James’ mother was initially hesitant to explore psychotropic medications and was concerned about stigmatization within the school system. She also seemed to avoid psychiatric treatment for her own depressive symptoms due to cultural and religious beliefs.

Health care provider concerns. Some PCPs may hesitate to explore medications due to limited knowledge and skill in dosing and titrating based on a child’s age, stage, and symptoms, and a perceived lack of competence in managing ADHD. This, too, can indirectly perpetuate existing health disparities. Furthermore, ADHD symptoms may be deemed a secondary or tertiary concern if other complex or urgent medical or undifferentiated developmental problems manifest.

Compounding matters is the limited dissemination of empiric research articles (including randomized controlled trials with representative samples) and limited education on the effectiveness and safety of psychopharmacologic interventions across the lifespan and different cultural and ethnic groups.⁴ Consequently, patients who struggle with unmanaged ADHD symptoms are more likely to have chronic mental health disorders, maladaptive behaviors, and other co-occurring conditions contributing to the complexity of individual needs, health care burdens, or justice system involvement; this is particularly true for those of racial and ethnic minorities.³³

Continue to: Impact of the COVID-19 pandemic

Impact of the COVID-19 pandemic. Patients—particularly those in minority or health disparity populations—who under normal circumstances might have been hesitant to seek help may have felt even more reluctant to do so during the COVID-19 pandemic. We have not yet learned the degree to which limited availability of preventive health care services, decreased routine visits, and fluctuating insurance coverage has impacted the diagnosis, management, or severity of childhood disorders during the past 2 years. Reports of national findings indicate that prolonged periods out of school and reduced daily structure were associated with increased disruptions in mood, sleep, and appetite, particularly among children with pre-existing pathologies. Evidence suggests that school-aged children experienced more anxiety, regressive behaviors, and parasomnias than they did before the pandemic, while adolescents experienced more isolation and depressive symptoms.^34,35

However, there remains a paucity of large-scale or representative studies that use an intersectional lens to examine the influence of COVID-19 on children with ADHD. Therefore, PCPs and IBHCs should refocus attention on possibly undiagnosed, stagnated, or regressed ADHD cases, as well as the adults who care for them. (See “5 ways to overcome Tx barriers and promote health equity.”)

THE CASE

During a follow-up visit 1 month later, the PCP confirmed the clinical impression of ADHD combined presentation with a clinical interview and review of the Strengths and Difficulties Questionnaire completed by James’ mother and the Vanderbilt Assessment Scales completed by James’ mother and teacher. The sleep diary indicated potential problems and apneas worthy of consults for pulmonary function testing, a sleep study, and otolaryngology examination. The PCP informed James’ mother on sleep hygiene strategies and ADHD medication options. She indicated that she wanted to pursue the referrals and behavioral modifications before starting any medication trial.

The PCP referred James to a developmental pediatrician for in-depth assessment of his overall development, learning, and functioning. The developmental pediatrician ultimately confirmed the diagnosis of ADHD, as well as motor and speech delays warranting physical, occupational, and speech therapies. The developmental pediatrician also referred James for targeted genetic testing because she suspected a genetic disorder (eg, XYY syndrome).

The PCP reconnected James and his mother to the IBHC to facilitate subspecialty and school-based care coordination and to provide in-office and home-based interventions. The IBHC assessed James’ emotional dysregulation and impulsivity as adversely impacting his interpersonal relationships and planned to address these issues with behavioral and ­parent–child interaction therapies and skills training during the course of 6 to 12 visits. James’ mother was encouraged to engage his teacher on his academic performance and to initiate a 504 Plan or IEP for in-school accommodations and support. The IBHC aided in tracking his assessments, referrals, follow-ups, access barriers, and treatment goals.

After 6 months, James had made only modest progress, and his mother requested that he begin a trial of medication. Based on his weight, symptoms, behavior patterns, and sleep habits, the PCP prescribed ­extended-release dexmethylphenidate 10 mg each morning, then extended-release clonidine 0.1 mg nightly. With team-based clinical management of pharmacologic, behavioral, physical, speech, and occupational therapies, James’ behavior and sleep improved, and the signs of a vocal tic diminished.

By the next school year, James demonstrated a marked improvement in impulse control, attention, and academic functioning. He followed up with the PCP at least quarterly for reassessment of his symptoms, growth, and experience of adverse effects, and to titrate medications accordingly. James and his mother continued to work closely with the IBHC monthly to engage interventions and to monitor his progress at home and school.

CORRESPONDENCE
Sundania J. W. Wonnum, PhD, LCSW, National Institute on Minority Health and Health Disparities, 6707 Democracy Boulevard, Suite 800, Bethesda, MD 20892; sundania.wonnum@nih.gov