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‘Concerning’ uptick in pediatric antipsychotic prescribing
“This study demonstrates a concerning trend in antipsychotic prescribing in children and adolescents,” study investigator Matthias Pierce, PhD, senior research fellow at the University of Manchester (England) Center for Women’s Mental Health, who jointly led the study, said in a news release.
“We do not think the changes in prescribing necessarily relate to changes in clinical need; rather, it may be more likely to reflect changes in prescribing practice by clinicians,” Dr. Pierce said.
The study was published online in The Lancet Psychiatry.
Increase in long-term use
Between 2000 and 2019, prescriptions for antipsychotics nearly doubled from 0.06% to 0.11%.
The investigators note that the U.K.’s National Institute for Health and Care Excellence has approved the use of some antipsychotics in patients younger than age 18 with schizophrenia, bipolar disorder, and severely aggressive behavior attributable to conduct disorder.
However, these data suggest antipsychotics are being prescribed for an increasingly broad range of conditions, most commonly autism, but also for attention-deficit/ hyperactivity disorder, tic disorders like Tourrette syndrome, and learning difficulties.
“Broadening use of antipsychotics in developing young people begs questions about their safety over time and demands more research on this topic,” senior author Kathryn Abel, MBBS, PhD, from the University of Manchester said in the news release.
During the study period, antipsychotic prescribing in primary care increased by an average of 3.3% per year and the rate of first prescriptions increased by 2.2% per year.
The data also suggest that more children and adolescents are taking these powerful drugs for longer periods of time. The proportion receiving antipsychotics for at least 6 months after an initial prescription rose from 41.9% in 2000 to 62.8% in 2018.
Prescribing inequities
From 2009 onwards, more than 90% of prescriptions were for atypical antipsychotics.
Over time, risperidone dominated, with more than 60% of all prescriptions, followed by aripiprazole, quetiapine, olanzapine, and haloperidol as the most prescribed antipsychotics.
Boys and older children aged 15-18 years were most likely to receive an antipsychotic. However, the increasing trends were evident in all groups.
The data also point to inequities in prescribing as a result of deprivation levels, with typical antipsychotics prescribed more frequently in more deprived areas over time.
Dr. Pierce said he hopes this study will “help clinicians to evaluate the prescribing of antipsychotics to children more fully and will encourage them to consider better access to alternatives.”
Dr. Abel noted that antipsychotic medications “continue to have a valuable role in the treatment of serious mental illness. These findings represent a descriptive account of antipsychotic prescribing to children and adolescents in the U.K. today and provide a window onto current practice.”
Findings are no surprise
Emily Simonoff, MD, professor of child and adolescent psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, offered perspective on the study in a statement from the U.K. nonprofit Science Media Centre.
“To clinicians, it will not be surprising that the authors demonstrate an increase in rates of prescriptions over that time period, as there has been a steadily emerging evidence base for the benefits of this group of medication for a range of different indications, which has been further supported by new licensing indications and recommendations from NICE,” Dr. Simonoff said.
For example, “there is good evidence for their benefits for other conditions such as irritability in autism spectrum disorder.
“However, it should also be noted that NICE recommendations for their use in many conditions is as part of a multimodal treatment plan, for example including psychological or behavioral interventions. It’s unclear from the study whether such recommendations were being followed or medication was being used on its own,” she added.
Dr. Simonoff also said it’s “reassuring” that prescribing rates remain very low in the youngest children and notes that the authors “rightly highlight the need for high-quality, longer-term studies on efficacy and, most importantly, adverse effects. This should be a research priority.”
The study had no funding. The authors report no relevant financial relationships. Dr. Simonoff is a member of the NICE guideline development group for the management of autism and has published on the efficacy of antipsychotic medication for irritability in autism.
A version of this article first appeared on Medscape.com.
“This study demonstrates a concerning trend in antipsychotic prescribing in children and adolescents,” study investigator Matthias Pierce, PhD, senior research fellow at the University of Manchester (England) Center for Women’s Mental Health, who jointly led the study, said in a news release.
“We do not think the changes in prescribing necessarily relate to changes in clinical need; rather, it may be more likely to reflect changes in prescribing practice by clinicians,” Dr. Pierce said.
The study was published online in The Lancet Psychiatry.
Increase in long-term use
Between 2000 and 2019, prescriptions for antipsychotics nearly doubled from 0.06% to 0.11%.
The investigators note that the U.K.’s National Institute for Health and Care Excellence has approved the use of some antipsychotics in patients younger than age 18 with schizophrenia, bipolar disorder, and severely aggressive behavior attributable to conduct disorder.
However, these data suggest antipsychotics are being prescribed for an increasingly broad range of conditions, most commonly autism, but also for attention-deficit/ hyperactivity disorder, tic disorders like Tourrette syndrome, and learning difficulties.
“Broadening use of antipsychotics in developing young people begs questions about their safety over time and demands more research on this topic,” senior author Kathryn Abel, MBBS, PhD, from the University of Manchester said in the news release.
During the study period, antipsychotic prescribing in primary care increased by an average of 3.3% per year and the rate of first prescriptions increased by 2.2% per year.
The data also suggest that more children and adolescents are taking these powerful drugs for longer periods of time. The proportion receiving antipsychotics for at least 6 months after an initial prescription rose from 41.9% in 2000 to 62.8% in 2018.
Prescribing inequities
From 2009 onwards, more than 90% of prescriptions were for atypical antipsychotics.
Over time, risperidone dominated, with more than 60% of all prescriptions, followed by aripiprazole, quetiapine, olanzapine, and haloperidol as the most prescribed antipsychotics.
Boys and older children aged 15-18 years were most likely to receive an antipsychotic. However, the increasing trends were evident in all groups.
The data also point to inequities in prescribing as a result of deprivation levels, with typical antipsychotics prescribed more frequently in more deprived areas over time.
Dr. Pierce said he hopes this study will “help clinicians to evaluate the prescribing of antipsychotics to children more fully and will encourage them to consider better access to alternatives.”
Dr. Abel noted that antipsychotic medications “continue to have a valuable role in the treatment of serious mental illness. These findings represent a descriptive account of antipsychotic prescribing to children and adolescents in the U.K. today and provide a window onto current practice.”
Findings are no surprise
Emily Simonoff, MD, professor of child and adolescent psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, offered perspective on the study in a statement from the U.K. nonprofit Science Media Centre.
“To clinicians, it will not be surprising that the authors demonstrate an increase in rates of prescriptions over that time period, as there has been a steadily emerging evidence base for the benefits of this group of medication for a range of different indications, which has been further supported by new licensing indications and recommendations from NICE,” Dr. Simonoff said.
For example, “there is good evidence for their benefits for other conditions such as irritability in autism spectrum disorder.
“However, it should also be noted that NICE recommendations for their use in many conditions is as part of a multimodal treatment plan, for example including psychological or behavioral interventions. It’s unclear from the study whether such recommendations were being followed or medication was being used on its own,” she added.
Dr. Simonoff also said it’s “reassuring” that prescribing rates remain very low in the youngest children and notes that the authors “rightly highlight the need for high-quality, longer-term studies on efficacy and, most importantly, adverse effects. This should be a research priority.”
The study had no funding. The authors report no relevant financial relationships. Dr. Simonoff is a member of the NICE guideline development group for the management of autism and has published on the efficacy of antipsychotic medication for irritability in autism.
A version of this article first appeared on Medscape.com.
“This study demonstrates a concerning trend in antipsychotic prescribing in children and adolescents,” study investigator Matthias Pierce, PhD, senior research fellow at the University of Manchester (England) Center for Women’s Mental Health, who jointly led the study, said in a news release.
“We do not think the changes in prescribing necessarily relate to changes in clinical need; rather, it may be more likely to reflect changes in prescribing practice by clinicians,” Dr. Pierce said.
The study was published online in The Lancet Psychiatry.
Increase in long-term use
Between 2000 and 2019, prescriptions for antipsychotics nearly doubled from 0.06% to 0.11%.
The investigators note that the U.K.’s National Institute for Health and Care Excellence has approved the use of some antipsychotics in patients younger than age 18 with schizophrenia, bipolar disorder, and severely aggressive behavior attributable to conduct disorder.
However, these data suggest antipsychotics are being prescribed for an increasingly broad range of conditions, most commonly autism, but also for attention-deficit/ hyperactivity disorder, tic disorders like Tourrette syndrome, and learning difficulties.
“Broadening use of antipsychotics in developing young people begs questions about their safety over time and demands more research on this topic,” senior author Kathryn Abel, MBBS, PhD, from the University of Manchester said in the news release.
During the study period, antipsychotic prescribing in primary care increased by an average of 3.3% per year and the rate of first prescriptions increased by 2.2% per year.
The data also suggest that more children and adolescents are taking these powerful drugs for longer periods of time. The proportion receiving antipsychotics for at least 6 months after an initial prescription rose from 41.9% in 2000 to 62.8% in 2018.
Prescribing inequities
From 2009 onwards, more than 90% of prescriptions were for atypical antipsychotics.
Over time, risperidone dominated, with more than 60% of all prescriptions, followed by aripiprazole, quetiapine, olanzapine, and haloperidol as the most prescribed antipsychotics.
Boys and older children aged 15-18 years were most likely to receive an antipsychotic. However, the increasing trends were evident in all groups.
The data also point to inequities in prescribing as a result of deprivation levels, with typical antipsychotics prescribed more frequently in more deprived areas over time.
Dr. Pierce said he hopes this study will “help clinicians to evaluate the prescribing of antipsychotics to children more fully and will encourage them to consider better access to alternatives.”
Dr. Abel noted that antipsychotic medications “continue to have a valuable role in the treatment of serious mental illness. These findings represent a descriptive account of antipsychotic prescribing to children and adolescents in the U.K. today and provide a window onto current practice.”
Findings are no surprise
Emily Simonoff, MD, professor of child and adolescent psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, offered perspective on the study in a statement from the U.K. nonprofit Science Media Centre.
“To clinicians, it will not be surprising that the authors demonstrate an increase in rates of prescriptions over that time period, as there has been a steadily emerging evidence base for the benefits of this group of medication for a range of different indications, which has been further supported by new licensing indications and recommendations from NICE,” Dr. Simonoff said.
For example, “there is good evidence for their benefits for other conditions such as irritability in autism spectrum disorder.
“However, it should also be noted that NICE recommendations for their use in many conditions is as part of a multimodal treatment plan, for example including psychological or behavioral interventions. It’s unclear from the study whether such recommendations were being followed or medication was being used on its own,” she added.
Dr. Simonoff also said it’s “reassuring” that prescribing rates remain very low in the youngest children and notes that the authors “rightly highlight the need for high-quality, longer-term studies on efficacy and, most importantly, adverse effects. This should be a research priority.”
The study had no funding. The authors report no relevant financial relationships. Dr. Simonoff is a member of the NICE guideline development group for the management of autism and has published on the efficacy of antipsychotic medication for irritability in autism.
A version of this article first appeared on Medscape.com.
FROM THE LANCET PSYCHIATRY
Kids with concussions may benefit from early return to school
The timing for return to school after a concussion has been the subject of guidelines, but data on how the timing of school returns affects later symptom burdens are limited, Christopher G. Vaughan, PhD, of Children’s National Hospital, Rockville, Md., and colleagues wrote.
Examining how the timing of return to school (RTS) affects later symptoms is needed to inform early postinjury management, they said.
In the new study published in JAMA Network Open, the researchers identified 1,630 children and teens aged 5-18 years who were treated for concussions at nine Canadian pediatric EDs. The primary outcome was symptom burden at 14 days post concussion, based on the Post-Concussion Symptom Inventory (PCSI). Early RTS was defined as missing fewer than 3 days of school post concussion.
Overall, the mean number of missed school days was 3.74 (excluding weekends). When divided by age, the mean number of missed days was 2.61 for children aged 5-7 years, 3.26 for those aged 8-12 years, and 4.71 for those aged 13-18 years.
Slightly more than half (53.7%) of the participants had an early RTS of 2 missed days or fewer. Later RTS was most common in the oldest age group, followed by the middle and younger age groups.
The researchers used a propensity score–matched analysis to determine associations. At 14 days, an early RTS was associated with reduced symptoms among 8- to 12-year-olds and 13- to 18-year-olds, though not in the youngest patients aged 5-7 years. In addition, the researchers created quantiles based on initial symptom ratings.
For the youngest age group, the association between early RTS and reduced symptoms at day 14 was higher among those with lower initial symptoms.
For the two older groups, the association was higher for those with higher initial symptoms (based on the PCSI).
The findings that earlier RTS was associated with a lower symptom burden at day 14 for those with higher levels of symptoms at baseline was surprising, but the mechanisms of the timing and effect of RTS requires more study, the researchers wrote in their discussion.
The effect of early RTS on symptoms may be in part related to factors such as “the benefits of socialization, reduced stress from not missing too much school, maintaining or returning to a normal sleep-wake schedule, and returning to light to moderate physical activity (gym class and recreational activities),” the researchers noted.
Another study related to recovery and concussion recently appeared in Neurology. In that study, the authors found that those athletes who took a longer time to recover from a sports-related concussion could still return to play with additional time off, but the methods and populations differed from the current study, which focused on RTS rather than returning to play.
The current study findings were limited by several factors including the lack of randomization for RTS timing and a lack of data on the variety of potential supports and accommodations students received, the researchers noted.
However, the results were strengthened by the large size and diverse nature of the concussions, and the roughly equal representation of boys and girls, they said.
Although randomized trials are needed to determine the best timing for RTS, the current study suggests that RTS within 2 days of a concussion is associated with improved symptoms, “and may directly or indirectly promote faster recovery,” they concluded.
Early return remains feasible for most children and teens
“Return to school can be a complicated issue for children and teens with concussions,” said Caitlyn Mooney, MD, a pediatrician and specialist in sports medicine at the University of Texas Health Science Center, San Antonio, said in an interview. Although much research has focused on diagnosis and return to sport after a concussion, there has been less focus on returning to school and learning. Various issues post concussion can make schooling difficult, and students may experience trouble with vision, concentration, sleep, headaches, and more.
Despite this knowledge, studies that specifically address recommended school protocols are limited, Dr. Mooney said. “Additionally, all concussions are different; while some students will need minimal help to return and succeed in school, others may need individualized learning plans and accommodations for school.” A return to school ideally would be a team-based approach with input from the parent, patient, physician, and educators.
“The theory of cognitive rest stems from the idea that a concussion causes metabolic dysfunction in the brain, and that increasing the metabolic demands of the brain can result in symptoms and a delayed return to school,” said Dr. Mooney.
Evidence suggests that those who start resting early after a concussion improve more quickly, “but there has been ongoing discussion over the years of what is the correct balance of cognitive rest to returning to modified activity,” she said. “This has led to the current general recommendation of rest for 24-48 hours followed by a gradual return to school as tolerated.”
Although the current study is large, it is limited by the lack of randomization, Dr. Mooney noted, therefore conclusions cannot be made that the cause of the improved symptoms is a quicker return to school.
However, the results support data from previous studies, in that both of the older age groups showed less disease burden at 14 days after an earlier return to school, she said.
“With prolonged absences, adolescents get isolated at home away from friends, and they may have increased mood symptoms. Additionally, I have found a high number of my patients who do not go to school as quickly have more sleep disturbance, which seems to increase symptoms such as difficulty concentrating or headaches,” she said. “It seems like the students do benefit from a routine schedule even if they have to have some accommodations at school, especially older students who may have more stress about missing school and falling behind on schoolwork.”
The message for pediatricians is that return to school should be individualized, Dr. Mooney said.
Although the current study does not dictate the optimal return to school, the results support those of previous studies in showing that, after 1-2 days of rest, an early return does not harm children and teens and may improve symptoms in many cases, she said. “In my experience, sometimes schools find it easier to keep the student at home rather than manage rest or special accommodations,” but the current study suggests that delaying return to school may not be the right choice for many patients.
“I hope this study empowers clinicians to advocate for these students, that the right place for them is in the classroom even with rest, extra time, or other accommodations,” said Dr. Mooney.
“Each concussion should be evaluated and treated individually; there will likely be a few who may need to stay home for a longer period of time, but this study suggests that the majority of students will suffer no ill effects from returning to the normal routine after a 2-day rest,” she noted.
The study was supported by the Canadian Institutes for Health Research. Dr. Vaughan and several coauthors disclosed being authors of the Postconcussion Symptom Inventory outside of the current study. Dr. Mooney had no financial conflicts to disclose.
The timing for return to school after a concussion has been the subject of guidelines, but data on how the timing of school returns affects later symptom burdens are limited, Christopher G. Vaughan, PhD, of Children’s National Hospital, Rockville, Md., and colleagues wrote.
Examining how the timing of return to school (RTS) affects later symptoms is needed to inform early postinjury management, they said.
In the new study published in JAMA Network Open, the researchers identified 1,630 children and teens aged 5-18 years who were treated for concussions at nine Canadian pediatric EDs. The primary outcome was symptom burden at 14 days post concussion, based on the Post-Concussion Symptom Inventory (PCSI). Early RTS was defined as missing fewer than 3 days of school post concussion.
Overall, the mean number of missed school days was 3.74 (excluding weekends). When divided by age, the mean number of missed days was 2.61 for children aged 5-7 years, 3.26 for those aged 8-12 years, and 4.71 for those aged 13-18 years.
Slightly more than half (53.7%) of the participants had an early RTS of 2 missed days or fewer. Later RTS was most common in the oldest age group, followed by the middle and younger age groups.
The researchers used a propensity score–matched analysis to determine associations. At 14 days, an early RTS was associated with reduced symptoms among 8- to 12-year-olds and 13- to 18-year-olds, though not in the youngest patients aged 5-7 years. In addition, the researchers created quantiles based on initial symptom ratings.
For the youngest age group, the association between early RTS and reduced symptoms at day 14 was higher among those with lower initial symptoms.
For the two older groups, the association was higher for those with higher initial symptoms (based on the PCSI).
The findings that earlier RTS was associated with a lower symptom burden at day 14 for those with higher levels of symptoms at baseline was surprising, but the mechanisms of the timing and effect of RTS requires more study, the researchers wrote in their discussion.
The effect of early RTS on symptoms may be in part related to factors such as “the benefits of socialization, reduced stress from not missing too much school, maintaining or returning to a normal sleep-wake schedule, and returning to light to moderate physical activity (gym class and recreational activities),” the researchers noted.
Another study related to recovery and concussion recently appeared in Neurology. In that study, the authors found that those athletes who took a longer time to recover from a sports-related concussion could still return to play with additional time off, but the methods and populations differed from the current study, which focused on RTS rather than returning to play.
The current study findings were limited by several factors including the lack of randomization for RTS timing and a lack of data on the variety of potential supports and accommodations students received, the researchers noted.
However, the results were strengthened by the large size and diverse nature of the concussions, and the roughly equal representation of boys and girls, they said.
Although randomized trials are needed to determine the best timing for RTS, the current study suggests that RTS within 2 days of a concussion is associated with improved symptoms, “and may directly or indirectly promote faster recovery,” they concluded.
Early return remains feasible for most children and teens
“Return to school can be a complicated issue for children and teens with concussions,” said Caitlyn Mooney, MD, a pediatrician and specialist in sports medicine at the University of Texas Health Science Center, San Antonio, said in an interview. Although much research has focused on diagnosis and return to sport after a concussion, there has been less focus on returning to school and learning. Various issues post concussion can make schooling difficult, and students may experience trouble with vision, concentration, sleep, headaches, and more.
Despite this knowledge, studies that specifically address recommended school protocols are limited, Dr. Mooney said. “Additionally, all concussions are different; while some students will need minimal help to return and succeed in school, others may need individualized learning plans and accommodations for school.” A return to school ideally would be a team-based approach with input from the parent, patient, physician, and educators.
“The theory of cognitive rest stems from the idea that a concussion causes metabolic dysfunction in the brain, and that increasing the metabolic demands of the brain can result in symptoms and a delayed return to school,” said Dr. Mooney.
Evidence suggests that those who start resting early after a concussion improve more quickly, “but there has been ongoing discussion over the years of what is the correct balance of cognitive rest to returning to modified activity,” she said. “This has led to the current general recommendation of rest for 24-48 hours followed by a gradual return to school as tolerated.”
Although the current study is large, it is limited by the lack of randomization, Dr. Mooney noted, therefore conclusions cannot be made that the cause of the improved symptoms is a quicker return to school.
However, the results support data from previous studies, in that both of the older age groups showed less disease burden at 14 days after an earlier return to school, she said.
“With prolonged absences, adolescents get isolated at home away from friends, and they may have increased mood symptoms. Additionally, I have found a high number of my patients who do not go to school as quickly have more sleep disturbance, which seems to increase symptoms such as difficulty concentrating or headaches,” she said. “It seems like the students do benefit from a routine schedule even if they have to have some accommodations at school, especially older students who may have more stress about missing school and falling behind on schoolwork.”
The message for pediatricians is that return to school should be individualized, Dr. Mooney said.
Although the current study does not dictate the optimal return to school, the results support those of previous studies in showing that, after 1-2 days of rest, an early return does not harm children and teens and may improve symptoms in many cases, she said. “In my experience, sometimes schools find it easier to keep the student at home rather than manage rest or special accommodations,” but the current study suggests that delaying return to school may not be the right choice for many patients.
“I hope this study empowers clinicians to advocate for these students, that the right place for them is in the classroom even with rest, extra time, or other accommodations,” said Dr. Mooney.
“Each concussion should be evaluated and treated individually; there will likely be a few who may need to stay home for a longer period of time, but this study suggests that the majority of students will suffer no ill effects from returning to the normal routine after a 2-day rest,” she noted.
The study was supported by the Canadian Institutes for Health Research. Dr. Vaughan and several coauthors disclosed being authors of the Postconcussion Symptom Inventory outside of the current study. Dr. Mooney had no financial conflicts to disclose.
The timing for return to school after a concussion has been the subject of guidelines, but data on how the timing of school returns affects later symptom burdens are limited, Christopher G. Vaughan, PhD, of Children’s National Hospital, Rockville, Md., and colleagues wrote.
Examining how the timing of return to school (RTS) affects later symptoms is needed to inform early postinjury management, they said.
In the new study published in JAMA Network Open, the researchers identified 1,630 children and teens aged 5-18 years who were treated for concussions at nine Canadian pediatric EDs. The primary outcome was symptom burden at 14 days post concussion, based on the Post-Concussion Symptom Inventory (PCSI). Early RTS was defined as missing fewer than 3 days of school post concussion.
Overall, the mean number of missed school days was 3.74 (excluding weekends). When divided by age, the mean number of missed days was 2.61 for children aged 5-7 years, 3.26 for those aged 8-12 years, and 4.71 for those aged 13-18 years.
Slightly more than half (53.7%) of the participants had an early RTS of 2 missed days or fewer. Later RTS was most common in the oldest age group, followed by the middle and younger age groups.
The researchers used a propensity score–matched analysis to determine associations. At 14 days, an early RTS was associated with reduced symptoms among 8- to 12-year-olds and 13- to 18-year-olds, though not in the youngest patients aged 5-7 years. In addition, the researchers created quantiles based on initial symptom ratings.
For the youngest age group, the association between early RTS and reduced symptoms at day 14 was higher among those with lower initial symptoms.
For the two older groups, the association was higher for those with higher initial symptoms (based on the PCSI).
The findings that earlier RTS was associated with a lower symptom burden at day 14 for those with higher levels of symptoms at baseline was surprising, but the mechanisms of the timing and effect of RTS requires more study, the researchers wrote in their discussion.
The effect of early RTS on symptoms may be in part related to factors such as “the benefits of socialization, reduced stress from not missing too much school, maintaining or returning to a normal sleep-wake schedule, and returning to light to moderate physical activity (gym class and recreational activities),” the researchers noted.
Another study related to recovery and concussion recently appeared in Neurology. In that study, the authors found that those athletes who took a longer time to recover from a sports-related concussion could still return to play with additional time off, but the methods and populations differed from the current study, which focused on RTS rather than returning to play.
The current study findings were limited by several factors including the lack of randomization for RTS timing and a lack of data on the variety of potential supports and accommodations students received, the researchers noted.
However, the results were strengthened by the large size and diverse nature of the concussions, and the roughly equal representation of boys and girls, they said.
Although randomized trials are needed to determine the best timing for RTS, the current study suggests that RTS within 2 days of a concussion is associated with improved symptoms, “and may directly or indirectly promote faster recovery,” they concluded.
Early return remains feasible for most children and teens
“Return to school can be a complicated issue for children and teens with concussions,” said Caitlyn Mooney, MD, a pediatrician and specialist in sports medicine at the University of Texas Health Science Center, San Antonio, said in an interview. Although much research has focused on diagnosis and return to sport after a concussion, there has been less focus on returning to school and learning. Various issues post concussion can make schooling difficult, and students may experience trouble with vision, concentration, sleep, headaches, and more.
Despite this knowledge, studies that specifically address recommended school protocols are limited, Dr. Mooney said. “Additionally, all concussions are different; while some students will need minimal help to return and succeed in school, others may need individualized learning plans and accommodations for school.” A return to school ideally would be a team-based approach with input from the parent, patient, physician, and educators.
“The theory of cognitive rest stems from the idea that a concussion causes metabolic dysfunction in the brain, and that increasing the metabolic demands of the brain can result in symptoms and a delayed return to school,” said Dr. Mooney.
Evidence suggests that those who start resting early after a concussion improve more quickly, “but there has been ongoing discussion over the years of what is the correct balance of cognitive rest to returning to modified activity,” she said. “This has led to the current general recommendation of rest for 24-48 hours followed by a gradual return to school as tolerated.”
Although the current study is large, it is limited by the lack of randomization, Dr. Mooney noted, therefore conclusions cannot be made that the cause of the improved symptoms is a quicker return to school.
However, the results support data from previous studies, in that both of the older age groups showed less disease burden at 14 days after an earlier return to school, she said.
“With prolonged absences, adolescents get isolated at home away from friends, and they may have increased mood symptoms. Additionally, I have found a high number of my patients who do not go to school as quickly have more sleep disturbance, which seems to increase symptoms such as difficulty concentrating or headaches,” she said. “It seems like the students do benefit from a routine schedule even if they have to have some accommodations at school, especially older students who may have more stress about missing school and falling behind on schoolwork.”
The message for pediatricians is that return to school should be individualized, Dr. Mooney said.
Although the current study does not dictate the optimal return to school, the results support those of previous studies in showing that, after 1-2 days of rest, an early return does not harm children and teens and may improve symptoms in many cases, she said. “In my experience, sometimes schools find it easier to keep the student at home rather than manage rest or special accommodations,” but the current study suggests that delaying return to school may not be the right choice for many patients.
“I hope this study empowers clinicians to advocate for these students, that the right place for them is in the classroom even with rest, extra time, or other accommodations,” said Dr. Mooney.
“Each concussion should be evaluated and treated individually; there will likely be a few who may need to stay home for a longer period of time, but this study suggests that the majority of students will suffer no ill effects from returning to the normal routine after a 2-day rest,” she noted.
The study was supported by the Canadian Institutes for Health Research. Dr. Vaughan and several coauthors disclosed being authors of the Postconcussion Symptom Inventory outside of the current study. Dr. Mooney had no financial conflicts to disclose.
FROM JAMA NETWORK OPEN
Emotional eating tied to risk of diastolic dysfunction
Eating in response to stress – known as emotional eating – was significantly associated with several markers of long-term cardiovascular damage, based on data from 1,109 individuals.
“We know diet plays a huge role in cardiovascular disease, but we have focused a lot of work on what you eat, not on what makes you eat” – the current study did exactly that, Martha Gulati, MD, who wasn’t involved in the study, said in an interview.
“Emotional eaters consume food to satisfy their brains rather than their stomachs,” study investigator Nicolas Girerd, MD, of the National Institute of Health and Medical Research (INSERM) and a cardiologist at the University Hospital of Nancy (France), wrote in a press release accompanying the study.
Diet plays a role in the development of cardiovascular disease (CVD), but the impact of eating behavior on long-term cardiovascular health remains unclear, wrote Dr. Girerd and colleagues. Previous research has yielded three common psychological dimensions for eating behavior: emotional eating, restrained eating, and external eating.
Both emotional eating and restrained eating have been linked to cardiovascular disease risk, the researchers noted. “Because of previous findings, we hypothesized that [emotional and/or restrained dimensions of eating behavior] are positively associated with cardiovascular damages, as well as with CV risk factors, such as metabolic syndrome,” they wrote.
In a study published in the European Journal of Preventive Cardiology, the researchers reviewed data from 916 adults and 193 adolescents who were participants in the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux), a longitudinal familial cohort in France. Cardiovascular data were collected at four medical visits as part of a full clinical examination between 1993 and 2016, with one visit every 5-10 years. Roughly one-third (31.0%) of the adults were overweight, 7.9% were obese, and 2.7% were underweight. The median age of the adults at the second visit was 44.7 years; the median age of the adolescent group was 15.2 years.
The primary outcome of cardiovascular damage was measured at the fourth visit. Eating behavior was assessed during the second visit using the Dutch Eating Behaviour Questionnaire (DEBQ), and participants were identified as emotional eaters, restrained eaters, or external eaters.
Among the adults, emotional eating was associated with a 38% increased risk of diastolic dysfunction (odds ratio, 1.38; P = .02), over an average follow-up of 13 years, and this association was mediated by stress in 32% of cases. Emotional eating also was positively linked with a higher carotid-femoral pulse-wave velocity (cfPWV-beta), indicative of increased arterial stiffness. However, none of the three dimensions of eating behavior was associated with cardiovascular damage among the adolescents. In addition, none of the eating-behavior dimensions was tied to metabolic syndrome in the adult group (this association was not measured in the adolescents).
Energy intake had no apparent impact on any associations between eating behavior and CVD measures, Dr. Girerd said in the press release. “We might expect that emotional eaters would consume high-calorie foods, which would in turn lead to cardiovascular problems, but this was not the case. One explanation is that we measured average calorie intake and emotional eaters may binge when stressed and then eat less at other times,” and that the resulting “yo-yo” pattern might negatively affect the heart and blood vessels more than stable food intake, he said.
The study findings were limited by several factors, including the observational design that prevented conclusions of causality, the researchers noted. Other limitations included the use of a nonvalidated scale to measure stress, the lack of data on physical activity, and the use of a mainly healthy population in a limited geographic area, which may limit generalizability, they said.
More research is needed in other contexts and larger cohorts, but the results were strengthened by the large study population and the complete data on eating behaviors and detailed health information, they wrote. The results support previous studies and suggest that patients with emotional eating behavior could benefit from emotion regulation skills training, including cognitive, behavioral, psychological, and interpersonal therapies used in other areas, and from pharmacological treatments, the researchers concluded.
The current study offers a unique and important perspective on the relationship between diet and cardiovascular disease, Dr. Gulati, director of preventive cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, told this news organization.
“Examining eating behavior and its relationship with cardiovascular effects in healthy individuals in this prospective way is quite interesting,” said Dr. Gulati, who was not involved in the study.
The researchers examined healthy people at baseline, inquired about their eating habits, and found that emotional eaters “have evidence of cardiovascular changes when compared with the other groups of eaters, after controlling for other risk factors that are associated with cardiovascular disease when following them for 13 years,” said Dr. Gulati, who was recently named Anita Dann Friedman Endowed Chair in Women’s Cardiovascular Medicine and Research at Cedars-Sinai. “This same finding wasn’t seen in adolescents, but this is probably because they are younger, and the effects aren’t seen. That is reassuring, because it means that the more we address eating behaviors, the more likely we are to reduce their effects to the heart,” she noted.
“This study is important because usually, as cardiologists or anyone in medicine, how we assess diet is by assessment of what food people eat; we don’t usually ask about what triggers them to eat,” Dr. Gulati said. “Eating behaviors based on their triggers ultimately affect food choice and food quantity, and help us understand weight changes during a lifetime,” she said.
“I think we don’t have the data to know that an eating behavior would be able to affect cardiac function,” said Dr. Gulati, “but I think we all might hypothesize that emotional eating may be associated with abnormal diastolic function simply through eating high-density food and weight gain.”
The current study did not show a relationship between eating behavior and metabolic syndrome, in contrast with prior studies, Dr. Gulati noted. However, “the authors report that the association between eating behaviors and diastolic dysfunction was mediated through the stress level,” Dr. Gulati said. “It is important to note that this European population was healthy at baseline, and also relatively healthy 13 years later, which makes these findings even more profound.”
Dr. Gulati said that she agrees with the study authors on the need to assess diet and eating behaviors when assessing cardiovascular risk in patient. “Diet assessment as part of prevention is central, but we should ask not only ‘what do you eat,’ but also ‘what makes you eat,’ ” she said.
More research is needed in other populations, Dr. Gulati added. The current study population was healthy at baseline and follow-up. Studies are needed in cohorts in the United States and in the developing world to see how the results might differ; as well as in rural America or in “food deserts” where food choices are limited.
Another research topic is the interplay between eating behaviors and social determinants of health, in terms of their effect on cardiovascular function, Dr. Gulati said, “and it will be valuable to follow this cohort further to see how these eating behaviors and these intermediate measures translate into cardiovascular outcomes.” Future studies should also examine whether the changes in cardiac function are reversible by interventions to modify eating behavior, particularly emotional eating, she said.
Supporters of the study included the Regional University Hospital Center of Nancy, the French Ministry of Solidarity and Health, and a public grant overseen by the French National Research Agency. The researchers had no financial conflicts to disclose.
Dr. Gulati, who serves on the editorial advisory board of MDedge Cardiology, had no financial conflicts to disclose.
Eating in response to stress – known as emotional eating – was significantly associated with several markers of long-term cardiovascular damage, based on data from 1,109 individuals.
“We know diet plays a huge role in cardiovascular disease, but we have focused a lot of work on what you eat, not on what makes you eat” – the current study did exactly that, Martha Gulati, MD, who wasn’t involved in the study, said in an interview.
“Emotional eaters consume food to satisfy their brains rather than their stomachs,” study investigator Nicolas Girerd, MD, of the National Institute of Health and Medical Research (INSERM) and a cardiologist at the University Hospital of Nancy (France), wrote in a press release accompanying the study.
Diet plays a role in the development of cardiovascular disease (CVD), but the impact of eating behavior on long-term cardiovascular health remains unclear, wrote Dr. Girerd and colleagues. Previous research has yielded three common psychological dimensions for eating behavior: emotional eating, restrained eating, and external eating.
Both emotional eating and restrained eating have been linked to cardiovascular disease risk, the researchers noted. “Because of previous findings, we hypothesized that [emotional and/or restrained dimensions of eating behavior] are positively associated with cardiovascular damages, as well as with CV risk factors, such as metabolic syndrome,” they wrote.
In a study published in the European Journal of Preventive Cardiology, the researchers reviewed data from 916 adults and 193 adolescents who were participants in the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux), a longitudinal familial cohort in France. Cardiovascular data were collected at four medical visits as part of a full clinical examination between 1993 and 2016, with one visit every 5-10 years. Roughly one-third (31.0%) of the adults were overweight, 7.9% were obese, and 2.7% were underweight. The median age of the adults at the second visit was 44.7 years; the median age of the adolescent group was 15.2 years.
The primary outcome of cardiovascular damage was measured at the fourth visit. Eating behavior was assessed during the second visit using the Dutch Eating Behaviour Questionnaire (DEBQ), and participants were identified as emotional eaters, restrained eaters, or external eaters.
Among the adults, emotional eating was associated with a 38% increased risk of diastolic dysfunction (odds ratio, 1.38; P = .02), over an average follow-up of 13 years, and this association was mediated by stress in 32% of cases. Emotional eating also was positively linked with a higher carotid-femoral pulse-wave velocity (cfPWV-beta), indicative of increased arterial stiffness. However, none of the three dimensions of eating behavior was associated with cardiovascular damage among the adolescents. In addition, none of the eating-behavior dimensions was tied to metabolic syndrome in the adult group (this association was not measured in the adolescents).
Energy intake had no apparent impact on any associations between eating behavior and CVD measures, Dr. Girerd said in the press release. “We might expect that emotional eaters would consume high-calorie foods, which would in turn lead to cardiovascular problems, but this was not the case. One explanation is that we measured average calorie intake and emotional eaters may binge when stressed and then eat less at other times,” and that the resulting “yo-yo” pattern might negatively affect the heart and blood vessels more than stable food intake, he said.
The study findings were limited by several factors, including the observational design that prevented conclusions of causality, the researchers noted. Other limitations included the use of a nonvalidated scale to measure stress, the lack of data on physical activity, and the use of a mainly healthy population in a limited geographic area, which may limit generalizability, they said.
More research is needed in other contexts and larger cohorts, but the results were strengthened by the large study population and the complete data on eating behaviors and detailed health information, they wrote. The results support previous studies and suggest that patients with emotional eating behavior could benefit from emotion regulation skills training, including cognitive, behavioral, psychological, and interpersonal therapies used in other areas, and from pharmacological treatments, the researchers concluded.
The current study offers a unique and important perspective on the relationship between diet and cardiovascular disease, Dr. Gulati, director of preventive cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, told this news organization.
“Examining eating behavior and its relationship with cardiovascular effects in healthy individuals in this prospective way is quite interesting,” said Dr. Gulati, who was not involved in the study.
The researchers examined healthy people at baseline, inquired about their eating habits, and found that emotional eaters “have evidence of cardiovascular changes when compared with the other groups of eaters, after controlling for other risk factors that are associated with cardiovascular disease when following them for 13 years,” said Dr. Gulati, who was recently named Anita Dann Friedman Endowed Chair in Women’s Cardiovascular Medicine and Research at Cedars-Sinai. “This same finding wasn’t seen in adolescents, but this is probably because they are younger, and the effects aren’t seen. That is reassuring, because it means that the more we address eating behaviors, the more likely we are to reduce their effects to the heart,” she noted.
“This study is important because usually, as cardiologists or anyone in medicine, how we assess diet is by assessment of what food people eat; we don’t usually ask about what triggers them to eat,” Dr. Gulati said. “Eating behaviors based on their triggers ultimately affect food choice and food quantity, and help us understand weight changes during a lifetime,” she said.
“I think we don’t have the data to know that an eating behavior would be able to affect cardiac function,” said Dr. Gulati, “but I think we all might hypothesize that emotional eating may be associated with abnormal diastolic function simply through eating high-density food and weight gain.”
The current study did not show a relationship between eating behavior and metabolic syndrome, in contrast with prior studies, Dr. Gulati noted. However, “the authors report that the association between eating behaviors and diastolic dysfunction was mediated through the stress level,” Dr. Gulati said. “It is important to note that this European population was healthy at baseline, and also relatively healthy 13 years later, which makes these findings even more profound.”
Dr. Gulati said that she agrees with the study authors on the need to assess diet and eating behaviors when assessing cardiovascular risk in patient. “Diet assessment as part of prevention is central, but we should ask not only ‘what do you eat,’ but also ‘what makes you eat,’ ” she said.
More research is needed in other populations, Dr. Gulati added. The current study population was healthy at baseline and follow-up. Studies are needed in cohorts in the United States and in the developing world to see how the results might differ; as well as in rural America or in “food deserts” where food choices are limited.
Another research topic is the interplay between eating behaviors and social determinants of health, in terms of their effect on cardiovascular function, Dr. Gulati said, “and it will be valuable to follow this cohort further to see how these eating behaviors and these intermediate measures translate into cardiovascular outcomes.” Future studies should also examine whether the changes in cardiac function are reversible by interventions to modify eating behavior, particularly emotional eating, she said.
Supporters of the study included the Regional University Hospital Center of Nancy, the French Ministry of Solidarity and Health, and a public grant overseen by the French National Research Agency. The researchers had no financial conflicts to disclose.
Dr. Gulati, who serves on the editorial advisory board of MDedge Cardiology, had no financial conflicts to disclose.
Eating in response to stress – known as emotional eating – was significantly associated with several markers of long-term cardiovascular damage, based on data from 1,109 individuals.
“We know diet plays a huge role in cardiovascular disease, but we have focused a lot of work on what you eat, not on what makes you eat” – the current study did exactly that, Martha Gulati, MD, who wasn’t involved in the study, said in an interview.
“Emotional eaters consume food to satisfy their brains rather than their stomachs,” study investigator Nicolas Girerd, MD, of the National Institute of Health and Medical Research (INSERM) and a cardiologist at the University Hospital of Nancy (France), wrote in a press release accompanying the study.
Diet plays a role in the development of cardiovascular disease (CVD), but the impact of eating behavior on long-term cardiovascular health remains unclear, wrote Dr. Girerd and colleagues. Previous research has yielded three common psychological dimensions for eating behavior: emotional eating, restrained eating, and external eating.
Both emotional eating and restrained eating have been linked to cardiovascular disease risk, the researchers noted. “Because of previous findings, we hypothesized that [emotional and/or restrained dimensions of eating behavior] are positively associated with cardiovascular damages, as well as with CV risk factors, such as metabolic syndrome,” they wrote.
In a study published in the European Journal of Preventive Cardiology, the researchers reviewed data from 916 adults and 193 adolescents who were participants in the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux), a longitudinal familial cohort in France. Cardiovascular data were collected at four medical visits as part of a full clinical examination between 1993 and 2016, with one visit every 5-10 years. Roughly one-third (31.0%) of the adults were overweight, 7.9% were obese, and 2.7% were underweight. The median age of the adults at the second visit was 44.7 years; the median age of the adolescent group was 15.2 years.
The primary outcome of cardiovascular damage was measured at the fourth visit. Eating behavior was assessed during the second visit using the Dutch Eating Behaviour Questionnaire (DEBQ), and participants were identified as emotional eaters, restrained eaters, or external eaters.
Among the adults, emotional eating was associated with a 38% increased risk of diastolic dysfunction (odds ratio, 1.38; P = .02), over an average follow-up of 13 years, and this association was mediated by stress in 32% of cases. Emotional eating also was positively linked with a higher carotid-femoral pulse-wave velocity (cfPWV-beta), indicative of increased arterial stiffness. However, none of the three dimensions of eating behavior was associated with cardiovascular damage among the adolescents. In addition, none of the eating-behavior dimensions was tied to metabolic syndrome in the adult group (this association was not measured in the adolescents).
Energy intake had no apparent impact on any associations between eating behavior and CVD measures, Dr. Girerd said in the press release. “We might expect that emotional eaters would consume high-calorie foods, which would in turn lead to cardiovascular problems, but this was not the case. One explanation is that we measured average calorie intake and emotional eaters may binge when stressed and then eat less at other times,” and that the resulting “yo-yo” pattern might negatively affect the heart and blood vessels more than stable food intake, he said.
The study findings were limited by several factors, including the observational design that prevented conclusions of causality, the researchers noted. Other limitations included the use of a nonvalidated scale to measure stress, the lack of data on physical activity, and the use of a mainly healthy population in a limited geographic area, which may limit generalizability, they said.
More research is needed in other contexts and larger cohorts, but the results were strengthened by the large study population and the complete data on eating behaviors and detailed health information, they wrote. The results support previous studies and suggest that patients with emotional eating behavior could benefit from emotion regulation skills training, including cognitive, behavioral, psychological, and interpersonal therapies used in other areas, and from pharmacological treatments, the researchers concluded.
The current study offers a unique and important perspective on the relationship between diet and cardiovascular disease, Dr. Gulati, director of preventive cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, told this news organization.
“Examining eating behavior and its relationship with cardiovascular effects in healthy individuals in this prospective way is quite interesting,” said Dr. Gulati, who was not involved in the study.
The researchers examined healthy people at baseline, inquired about their eating habits, and found that emotional eaters “have evidence of cardiovascular changes when compared with the other groups of eaters, after controlling for other risk factors that are associated with cardiovascular disease when following them for 13 years,” said Dr. Gulati, who was recently named Anita Dann Friedman Endowed Chair in Women’s Cardiovascular Medicine and Research at Cedars-Sinai. “This same finding wasn’t seen in adolescents, but this is probably because they are younger, and the effects aren’t seen. That is reassuring, because it means that the more we address eating behaviors, the more likely we are to reduce their effects to the heart,” she noted.
“This study is important because usually, as cardiologists or anyone in medicine, how we assess diet is by assessment of what food people eat; we don’t usually ask about what triggers them to eat,” Dr. Gulati said. “Eating behaviors based on their triggers ultimately affect food choice and food quantity, and help us understand weight changes during a lifetime,” she said.
“I think we don’t have the data to know that an eating behavior would be able to affect cardiac function,” said Dr. Gulati, “but I think we all might hypothesize that emotional eating may be associated with abnormal diastolic function simply through eating high-density food and weight gain.”
The current study did not show a relationship between eating behavior and metabolic syndrome, in contrast with prior studies, Dr. Gulati noted. However, “the authors report that the association between eating behaviors and diastolic dysfunction was mediated through the stress level,” Dr. Gulati said. “It is important to note that this European population was healthy at baseline, and also relatively healthy 13 years later, which makes these findings even more profound.”
Dr. Gulati said that she agrees with the study authors on the need to assess diet and eating behaviors when assessing cardiovascular risk in patient. “Diet assessment as part of prevention is central, but we should ask not only ‘what do you eat,’ but also ‘what makes you eat,’ ” she said.
More research is needed in other populations, Dr. Gulati added. The current study population was healthy at baseline and follow-up. Studies are needed in cohorts in the United States and in the developing world to see how the results might differ; as well as in rural America or in “food deserts” where food choices are limited.
Another research topic is the interplay between eating behaviors and social determinants of health, in terms of their effect on cardiovascular function, Dr. Gulati said, “and it will be valuable to follow this cohort further to see how these eating behaviors and these intermediate measures translate into cardiovascular outcomes.” Future studies should also examine whether the changes in cardiac function are reversible by interventions to modify eating behavior, particularly emotional eating, she said.
Supporters of the study included the Regional University Hospital Center of Nancy, the French Ministry of Solidarity and Health, and a public grant overseen by the French National Research Agency. The researchers had no financial conflicts to disclose.
Dr. Gulati, who serves on the editorial advisory board of MDedge Cardiology, had no financial conflicts to disclose.
FROM THE EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
More support for MDMA-assisted psychotherapy for PTSD
The MAPP2 study is the second randomized, double-blind, placebo-controlled study to demonstrate the safety and efficacy of MDMA-assisted therapy for PTSD.
The investigators confirm results of the MAPP1 study, which were published in Nature Medicine. Patients who received MDMA-assisted psychotherapy in MAPP1 demonstrated greater improvement in PTSD symptoms, mood, and empathy, compared with participants who received psychotherapy with placebo.
The design of the MAPP2 study was similar to that of MAPP1, and its results were similar, the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS), which sponsored MAPP1 and MAPP2, said in a news release.
No specific results from MAPP2 were provided at this time. The full data from MAPP2 are expected to be published in a peer-reviewed journal later this year, and a new drug application to the U.S. Food and Drug Administration will follow.
The FDA granted breakthrough therapy designation to MDMA as an adjunct to psychotherapy for adults with PTSD in 2017.
MAPS was founded in 1986 to fund and facilitate research into the potential of psychedelic-assisted therapies; to educate the public about psychedelics for medical, social, and spiritual use; and to advocate for drug policy reform.
“When I first articulated a plan to legitimize a psychedelic-assisted therapy through FDA approval, many people said it was impossible,” Rick Doblin, PhD, founder and executive director of MAPS, said in the news release.
“Thirty-seven years later, we are on the precipice of bringing a novel therapy to the millions of Americans living with PTSD who haven’t found relief through current treatments,” said Dr. Doblin.
“The impossible became possible through the bravery of clinical trial participants, the compassion of mental health practitioners, and the generosity of thousands of donors. Today, we can imagine that MDMA-assisted therapy for PTSD may soon be available and accessible to all who could benefit,” Dr. Doblin added.
According to MAPS, phase 2 trials are being planned or conducted regarding the efficacy of MDMA-assisted therapies for substance use disorder and eating disorders, as well as couples therapy and group therapy among veterans.
Currently, no psychedelic-assisted therapy has been approved by the FDA or other regulatory authorities.
A version of this article first appeared on Medscape.com.
The MAPP2 study is the second randomized, double-blind, placebo-controlled study to demonstrate the safety and efficacy of MDMA-assisted therapy for PTSD.
The investigators confirm results of the MAPP1 study, which were published in Nature Medicine. Patients who received MDMA-assisted psychotherapy in MAPP1 demonstrated greater improvement in PTSD symptoms, mood, and empathy, compared with participants who received psychotherapy with placebo.
The design of the MAPP2 study was similar to that of MAPP1, and its results were similar, the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS), which sponsored MAPP1 and MAPP2, said in a news release.
No specific results from MAPP2 were provided at this time. The full data from MAPP2 are expected to be published in a peer-reviewed journal later this year, and a new drug application to the U.S. Food and Drug Administration will follow.
The FDA granted breakthrough therapy designation to MDMA as an adjunct to psychotherapy for adults with PTSD in 2017.
MAPS was founded in 1986 to fund and facilitate research into the potential of psychedelic-assisted therapies; to educate the public about psychedelics for medical, social, and spiritual use; and to advocate for drug policy reform.
“When I first articulated a plan to legitimize a psychedelic-assisted therapy through FDA approval, many people said it was impossible,” Rick Doblin, PhD, founder and executive director of MAPS, said in the news release.
“Thirty-seven years later, we are on the precipice of bringing a novel therapy to the millions of Americans living with PTSD who haven’t found relief through current treatments,” said Dr. Doblin.
“The impossible became possible through the bravery of clinical trial participants, the compassion of mental health practitioners, and the generosity of thousands of donors. Today, we can imagine that MDMA-assisted therapy for PTSD may soon be available and accessible to all who could benefit,” Dr. Doblin added.
According to MAPS, phase 2 trials are being planned or conducted regarding the efficacy of MDMA-assisted therapies for substance use disorder and eating disorders, as well as couples therapy and group therapy among veterans.
Currently, no psychedelic-assisted therapy has been approved by the FDA or other regulatory authorities.
A version of this article first appeared on Medscape.com.
The MAPP2 study is the second randomized, double-blind, placebo-controlled study to demonstrate the safety and efficacy of MDMA-assisted therapy for PTSD.
The investigators confirm results of the MAPP1 study, which were published in Nature Medicine. Patients who received MDMA-assisted psychotherapy in MAPP1 demonstrated greater improvement in PTSD symptoms, mood, and empathy, compared with participants who received psychotherapy with placebo.
The design of the MAPP2 study was similar to that of MAPP1, and its results were similar, the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS), which sponsored MAPP1 and MAPP2, said in a news release.
No specific results from MAPP2 were provided at this time. The full data from MAPP2 are expected to be published in a peer-reviewed journal later this year, and a new drug application to the U.S. Food and Drug Administration will follow.
The FDA granted breakthrough therapy designation to MDMA as an adjunct to psychotherapy for adults with PTSD in 2017.
MAPS was founded in 1986 to fund and facilitate research into the potential of psychedelic-assisted therapies; to educate the public about psychedelics for medical, social, and spiritual use; and to advocate for drug policy reform.
“When I first articulated a plan to legitimize a psychedelic-assisted therapy through FDA approval, many people said it was impossible,” Rick Doblin, PhD, founder and executive director of MAPS, said in the news release.
“Thirty-seven years later, we are on the precipice of bringing a novel therapy to the millions of Americans living with PTSD who haven’t found relief through current treatments,” said Dr. Doblin.
“The impossible became possible through the bravery of clinical trial participants, the compassion of mental health practitioners, and the generosity of thousands of donors. Today, we can imagine that MDMA-assisted therapy for PTSD may soon be available and accessible to all who could benefit,” Dr. Doblin added.
According to MAPS, phase 2 trials are being planned or conducted regarding the efficacy of MDMA-assisted therapies for substance use disorder and eating disorders, as well as couples therapy and group therapy among veterans.
Currently, no psychedelic-assisted therapy has been approved by the FDA or other regulatory authorities.
A version of this article first appeared on Medscape.com.
HRT may prevent Alzheimer’s in high-risk women
new research suggests.
Results from a cohort study of almost 1,200 women showed that use of HRT was associated with higher delayed memory scores and larger entorhinal and hippocampal brain volumes – areas that are affected early by Alzheimer’s disease (AD) pathology.
HRT was also found to be most effective, as seen by larger hippocampal volume, when introduced during early perimenopause.
“Clinicians are very much aware of the susceptibility of women to cognitive disturbances during menopause,” lead author Rasha Saleh, MD, senior research associate, University of East Anglia (England), said in an interview.
“Identifying the at-risk APOE4 women and early HRT introduction can be of benefit. Confirming our findings in a clinical trial would be the next step forward,” Dr. Saleh said.
The findings were published online in Alzheimer’s Research and Therapy.
Personalized approaches
Dr. Saleh noted that estrogen receptors are localized in various areas of the brain, including cognition-related areas. Estrogen regulates such things as neuroinflammatory status, glucose utilization, and lipid metabolism.
“The decline of estrogen during menopause can lead to disturbance in these functions, which can accelerate AD-related pathology,” she said.
HRT during the menopausal transition and afterward is “being considered as a strategy to mitigate cognitive decline,” the investigators wrote. Early observational studies have suggested that oral estrogen “may be protective against dementia,” but results of clinical trials have been inconsistent, and some have even shown “harmful effects.”
The current researchers were “interested in the personalized approaches in the prevention of AD,” Dr. Saleh said. Preclinical and pilot data from her group have shown that women with APOE4 have “better cognitive test scores with nutritional and hormonal interventions.”
This led Dr. Saleh to hypothesize that HRT would be of more cognitive benefit for those with versus without APOE4, particularly when introduced early during the menopausal transition.
To investigate this hypothesis, the researchers analyzed baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort. This project was initiated in 2015 with the aim of developing longitudinal models over the entire course of AD prior to dementia clinical diagnosis.
Participants were recruited from 10 European countries. All were required to be at least 50 years old, to have not been diagnosed with dementia at baseline, and to have no medical or psychiatric illness that could potentially exclude them from further research.
The current study included 1,178 women (mean age, 65.1 years), who were divided by genotype into non-APOE4 and APOE4 groups. HRT treatment for current or previous users included estrogen alone or estrogen plus progestogens via oral or transdermal administration routes, and at different doses.
The four tests used to assess cognition were the Mini-Mental State Examination dot counting to evaluate verbal working memory, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score, the Four Mountain Test, and the supermarket trolley virtual reality test.
Brain MRI data were collected. The researchers focused on the medial temporal lobe as the “main brain region regulating cognition and memory processing.” This lobe includes the hippocampus, the parahippocampus, the entorhinal cortex, and the amygdala.
‘Critical window’
The researchers found a “trend” toward an APOE-HRT interaction (P-interaction = .097) for the total RBANS score. In particular, it was significant for the RBANS delayed memory index, where scores were consistently higher for women with APOE4 who had received HRT, compared with all other groups (P-interaction = .009).
Within-genotype group comparisons showed that HRT users had a higher RBANS total scale score and delayed memory index (P = .045 and P = .002, respectively), but only among APOE4 carriers. Effect size analyses showed a large effect of HRT use on the Four Mountain Test score and the supermarket trolley virtual reality test score (Cohen’s d = 0.988 and 1.2, respectively).
“This large effect was found only in APOE4 carriers,” the investigators noted.
Similarly, a moderate to large effect of HRT on the left entorhinal volume was observed in APOE4 carriers (Cohen’s d = 0.63).
In members of the APOE4 group who received HRT, the left entorhinal and left and right amygdala volumes were larger, compared with both no-APOE4 and non-HRT users (P-interaction = .002, .003, and .005, respectively). Similar trends were observed for the right entorhinal volume (P = .074).
In addition, among HRT users, the left entorhinal volume was larger (P = .03); the right and left anterior cingulate gyrus volumes were smaller (P = .003 and .062, respectively); and the left superior frontal gyrus volume was larger (P = .009) in comparison with women who did not receive HRT, independently of their APOE genotype.
Early use of HRT among APOE4 carriers was associated with larger right and left hippocampal volume (P = .035 and P = .028, respectively) – an association not found in non-APOE4 carriers. The association was also not significant when participants were not stratified by APOE genotype.
“The key important point here is the timing, or the ‘critical window,’ when HRT can be of most benefit,” Dr. Saleh said. “This is most beneficial when introduced early, before the neuropathology becomes irreversible.”
Study limitations include its cross-sectional design, which precludes the establishment of a causal relationship, and the fact that information regarding the type and dose of estrogen was not available for all participants.
HRT is not without risk, Dr. Saleh noted. She recommended that clinicians “carry out various screening tests to make sure that a woman is eligible for HRT and not at risk of hypercoagulability, for instance.”
Risk-benefit ratio
In a comment, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, called the study “exactly the kind of work that needs to be done.”
Dr. Fillit, who was not involved with the current research, is a clinical professor of geriatric medicine, palliative care medicine, and neuroscience at Mount Sinai Hospital, New York.
He compared the process with that of osteoporosis. “We know that if women are treated [with HRT] at the time of the menopause, you can prevent the rapid bone loss that occurs with rapid estrogen loss. But if you wait 5, 10 years out, once the bone loss has occurred, the HRT doesn’t really have any impact on osteoporosis risk because the horse is already out of the barn,” he said.
Although HRT carries risks, “they can clearly be managed; and if it’s proven that estrogen or hormone replacement around the time of the menopause can be protective [against AD], the risk-benefit ratio of HRT could be in favor of treatment,” Dr. Fillit added.
The study was conducted as part of the Medical Research Council NuBrain Consortium. The investigators and Dr. Fillit reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Results from a cohort study of almost 1,200 women showed that use of HRT was associated with higher delayed memory scores and larger entorhinal and hippocampal brain volumes – areas that are affected early by Alzheimer’s disease (AD) pathology.
HRT was also found to be most effective, as seen by larger hippocampal volume, when introduced during early perimenopause.
“Clinicians are very much aware of the susceptibility of women to cognitive disturbances during menopause,” lead author Rasha Saleh, MD, senior research associate, University of East Anglia (England), said in an interview.
“Identifying the at-risk APOE4 women and early HRT introduction can be of benefit. Confirming our findings in a clinical trial would be the next step forward,” Dr. Saleh said.
The findings were published online in Alzheimer’s Research and Therapy.
Personalized approaches
Dr. Saleh noted that estrogen receptors are localized in various areas of the brain, including cognition-related areas. Estrogen regulates such things as neuroinflammatory status, glucose utilization, and lipid metabolism.
“The decline of estrogen during menopause can lead to disturbance in these functions, which can accelerate AD-related pathology,” she said.
HRT during the menopausal transition and afterward is “being considered as a strategy to mitigate cognitive decline,” the investigators wrote. Early observational studies have suggested that oral estrogen “may be protective against dementia,” but results of clinical trials have been inconsistent, and some have even shown “harmful effects.”
The current researchers were “interested in the personalized approaches in the prevention of AD,” Dr. Saleh said. Preclinical and pilot data from her group have shown that women with APOE4 have “better cognitive test scores with nutritional and hormonal interventions.”
This led Dr. Saleh to hypothesize that HRT would be of more cognitive benefit for those with versus without APOE4, particularly when introduced early during the menopausal transition.
To investigate this hypothesis, the researchers analyzed baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort. This project was initiated in 2015 with the aim of developing longitudinal models over the entire course of AD prior to dementia clinical diagnosis.
Participants were recruited from 10 European countries. All were required to be at least 50 years old, to have not been diagnosed with dementia at baseline, and to have no medical or psychiatric illness that could potentially exclude them from further research.
The current study included 1,178 women (mean age, 65.1 years), who were divided by genotype into non-APOE4 and APOE4 groups. HRT treatment for current or previous users included estrogen alone or estrogen plus progestogens via oral or transdermal administration routes, and at different doses.
The four tests used to assess cognition were the Mini-Mental State Examination dot counting to evaluate verbal working memory, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score, the Four Mountain Test, and the supermarket trolley virtual reality test.
Brain MRI data were collected. The researchers focused on the medial temporal lobe as the “main brain region regulating cognition and memory processing.” This lobe includes the hippocampus, the parahippocampus, the entorhinal cortex, and the amygdala.
‘Critical window’
The researchers found a “trend” toward an APOE-HRT interaction (P-interaction = .097) for the total RBANS score. In particular, it was significant for the RBANS delayed memory index, where scores were consistently higher for women with APOE4 who had received HRT, compared with all other groups (P-interaction = .009).
Within-genotype group comparisons showed that HRT users had a higher RBANS total scale score and delayed memory index (P = .045 and P = .002, respectively), but only among APOE4 carriers. Effect size analyses showed a large effect of HRT use on the Four Mountain Test score and the supermarket trolley virtual reality test score (Cohen’s d = 0.988 and 1.2, respectively).
“This large effect was found only in APOE4 carriers,” the investigators noted.
Similarly, a moderate to large effect of HRT on the left entorhinal volume was observed in APOE4 carriers (Cohen’s d = 0.63).
In members of the APOE4 group who received HRT, the left entorhinal and left and right amygdala volumes were larger, compared with both no-APOE4 and non-HRT users (P-interaction = .002, .003, and .005, respectively). Similar trends were observed for the right entorhinal volume (P = .074).
In addition, among HRT users, the left entorhinal volume was larger (P = .03); the right and left anterior cingulate gyrus volumes were smaller (P = .003 and .062, respectively); and the left superior frontal gyrus volume was larger (P = .009) in comparison with women who did not receive HRT, independently of their APOE genotype.
Early use of HRT among APOE4 carriers was associated with larger right and left hippocampal volume (P = .035 and P = .028, respectively) – an association not found in non-APOE4 carriers. The association was also not significant when participants were not stratified by APOE genotype.
“The key important point here is the timing, or the ‘critical window,’ when HRT can be of most benefit,” Dr. Saleh said. “This is most beneficial when introduced early, before the neuropathology becomes irreversible.”
Study limitations include its cross-sectional design, which precludes the establishment of a causal relationship, and the fact that information regarding the type and dose of estrogen was not available for all participants.
HRT is not without risk, Dr. Saleh noted. She recommended that clinicians “carry out various screening tests to make sure that a woman is eligible for HRT and not at risk of hypercoagulability, for instance.”
Risk-benefit ratio
In a comment, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, called the study “exactly the kind of work that needs to be done.”
Dr. Fillit, who was not involved with the current research, is a clinical professor of geriatric medicine, palliative care medicine, and neuroscience at Mount Sinai Hospital, New York.
He compared the process with that of osteoporosis. “We know that if women are treated [with HRT] at the time of the menopause, you can prevent the rapid bone loss that occurs with rapid estrogen loss. But if you wait 5, 10 years out, once the bone loss has occurred, the HRT doesn’t really have any impact on osteoporosis risk because the horse is already out of the barn,” he said.
Although HRT carries risks, “they can clearly be managed; and if it’s proven that estrogen or hormone replacement around the time of the menopause can be protective [against AD], the risk-benefit ratio of HRT could be in favor of treatment,” Dr. Fillit added.
The study was conducted as part of the Medical Research Council NuBrain Consortium. The investigators and Dr. Fillit reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Results from a cohort study of almost 1,200 women showed that use of HRT was associated with higher delayed memory scores and larger entorhinal and hippocampal brain volumes – areas that are affected early by Alzheimer’s disease (AD) pathology.
HRT was also found to be most effective, as seen by larger hippocampal volume, when introduced during early perimenopause.
“Clinicians are very much aware of the susceptibility of women to cognitive disturbances during menopause,” lead author Rasha Saleh, MD, senior research associate, University of East Anglia (England), said in an interview.
“Identifying the at-risk APOE4 women and early HRT introduction can be of benefit. Confirming our findings in a clinical trial would be the next step forward,” Dr. Saleh said.
The findings were published online in Alzheimer’s Research and Therapy.
Personalized approaches
Dr. Saleh noted that estrogen receptors are localized in various areas of the brain, including cognition-related areas. Estrogen regulates such things as neuroinflammatory status, glucose utilization, and lipid metabolism.
“The decline of estrogen during menopause can lead to disturbance in these functions, which can accelerate AD-related pathology,” she said.
HRT during the menopausal transition and afterward is “being considered as a strategy to mitigate cognitive decline,” the investigators wrote. Early observational studies have suggested that oral estrogen “may be protective against dementia,” but results of clinical trials have been inconsistent, and some have even shown “harmful effects.”
The current researchers were “interested in the personalized approaches in the prevention of AD,” Dr. Saleh said. Preclinical and pilot data from her group have shown that women with APOE4 have “better cognitive test scores with nutritional and hormonal interventions.”
This led Dr. Saleh to hypothesize that HRT would be of more cognitive benefit for those with versus without APOE4, particularly when introduced early during the menopausal transition.
To investigate this hypothesis, the researchers analyzed baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort. This project was initiated in 2015 with the aim of developing longitudinal models over the entire course of AD prior to dementia clinical diagnosis.
Participants were recruited from 10 European countries. All were required to be at least 50 years old, to have not been diagnosed with dementia at baseline, and to have no medical or psychiatric illness that could potentially exclude them from further research.
The current study included 1,178 women (mean age, 65.1 years), who were divided by genotype into non-APOE4 and APOE4 groups. HRT treatment for current or previous users included estrogen alone or estrogen plus progestogens via oral or transdermal administration routes, and at different doses.
The four tests used to assess cognition were the Mini-Mental State Examination dot counting to evaluate verbal working memory, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score, the Four Mountain Test, and the supermarket trolley virtual reality test.
Brain MRI data were collected. The researchers focused on the medial temporal lobe as the “main brain region regulating cognition and memory processing.” This lobe includes the hippocampus, the parahippocampus, the entorhinal cortex, and the amygdala.
‘Critical window’
The researchers found a “trend” toward an APOE-HRT interaction (P-interaction = .097) for the total RBANS score. In particular, it was significant for the RBANS delayed memory index, where scores were consistently higher for women with APOE4 who had received HRT, compared with all other groups (P-interaction = .009).
Within-genotype group comparisons showed that HRT users had a higher RBANS total scale score and delayed memory index (P = .045 and P = .002, respectively), but only among APOE4 carriers. Effect size analyses showed a large effect of HRT use on the Four Mountain Test score and the supermarket trolley virtual reality test score (Cohen’s d = 0.988 and 1.2, respectively).
“This large effect was found only in APOE4 carriers,” the investigators noted.
Similarly, a moderate to large effect of HRT on the left entorhinal volume was observed in APOE4 carriers (Cohen’s d = 0.63).
In members of the APOE4 group who received HRT, the left entorhinal and left and right amygdala volumes were larger, compared with both no-APOE4 and non-HRT users (P-interaction = .002, .003, and .005, respectively). Similar trends were observed for the right entorhinal volume (P = .074).
In addition, among HRT users, the left entorhinal volume was larger (P = .03); the right and left anterior cingulate gyrus volumes were smaller (P = .003 and .062, respectively); and the left superior frontal gyrus volume was larger (P = .009) in comparison with women who did not receive HRT, independently of their APOE genotype.
Early use of HRT among APOE4 carriers was associated with larger right and left hippocampal volume (P = .035 and P = .028, respectively) – an association not found in non-APOE4 carriers. The association was also not significant when participants were not stratified by APOE genotype.
“The key important point here is the timing, or the ‘critical window,’ when HRT can be of most benefit,” Dr. Saleh said. “This is most beneficial when introduced early, before the neuropathology becomes irreversible.”
Study limitations include its cross-sectional design, which precludes the establishment of a causal relationship, and the fact that information regarding the type and dose of estrogen was not available for all participants.
HRT is not without risk, Dr. Saleh noted. She recommended that clinicians “carry out various screening tests to make sure that a woman is eligible for HRT and not at risk of hypercoagulability, for instance.”
Risk-benefit ratio
In a comment, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, called the study “exactly the kind of work that needs to be done.”
Dr. Fillit, who was not involved with the current research, is a clinical professor of geriatric medicine, palliative care medicine, and neuroscience at Mount Sinai Hospital, New York.
He compared the process with that of osteoporosis. “We know that if women are treated [with HRT] at the time of the menopause, you can prevent the rapid bone loss that occurs with rapid estrogen loss. But if you wait 5, 10 years out, once the bone loss has occurred, the HRT doesn’t really have any impact on osteoporosis risk because the horse is already out of the barn,” he said.
Although HRT carries risks, “they can clearly be managed; and if it’s proven that estrogen or hormone replacement around the time of the menopause can be protective [against AD], the risk-benefit ratio of HRT could be in favor of treatment,” Dr. Fillit added.
The study was conducted as part of the Medical Research Council NuBrain Consortium. The investigators and Dr. Fillit reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ALZHEIMER’S RESEARCH AND THERAPY
The Respect for Marriage Act: How this law supports the health and well-being of LGBTQ+ youth
Childhood and adolescence are periods of life with rapid growth and development in which the psychosocial factors of one’s environment can have a profound effect on health. There is increasing evidence that adverse childhood experiences (ACEs) can have significant negative effects on long-term health with effects persisting into subsequent generations.1 Youth themselves, however, often do not have the voice, ability, or political power to advocate for safe and more supportive environments that are essential to their well-being. Thus, advocacy has been central to the profession of pediatrics since its inception, where providers can partner with their patients, families, and communities to push for changes in the environments in which youth live and grow.2
LGBTQ+ youth are known to be at increased risk for ACEs because of the stress that comes from being part of a minority group and the discrimination they experience by their families, communities, and society at large. These factors within their environments have been shown to be associated with increased rates of anxiety, depression, substance use, sexually transmitted infections, and homelessness.3 As with other health outcomes that have been linked to the social determinants of health, these disparities are not inevitable and could be greatly improved upon through advocacy and changes in the environments of LGBTQ+ youth.
Marriage equality (the recognition that same-sex couples have the same legal right to marry as opposite-sex couples) has been shown to be not only a political issue, but one that affects health. The debates surrounding marriage equality have contributed to minority stress by questioning the validity of same-sex relationships and assigning them less value relative to opposite-sex relationships.4 In 1996, the U.S. Congress passed the Defense of Marriage Act (DOMA), which federally defined marriage as being legally recognized only between opposite-sex couples.
Individual states then continued the marriage equality debate by passing individual state laws either allowing or prohibiting same-sex marriage. During this time, it was shown that, in states where same-sex marriage was legally prohibited, LGBTQ+ adults reported significantly higher rates of generalized anxiety disorder, alcohol use disorder, any mood disorder, and psychiatric comorbidity when compared with states without a legal ban on same-sex marriage.5
Using data from the Youth Risk Behavior Surveillance System, it was shown that state policies recognizing same-sex marriage were associated with a 7% relative reduction in suicide attempts reported by adolescent sexual minority students compared with before these policies.6 It was also shown that children with same-sex parents were overall less likely to have private health insurance, but this disparity was improved in states that legally recognized same-sex marriage and allowed second-parent adoptions.7
In 2013, the U.S. Supreme Court ruled that DOMA was unconstitutional, requiring the federal government to legally recognize same-sex marriages for the purposes of federal benefits. In 2015, the U.S. Supreme Court further ruled that same-sex couples are guaranteed the fundamental right to marry, requiring that all states issue marriage licenses to same-sex couples. These rulings were associated with a decrease in reported levels of stigma over time and increased reported levels of family support, particularly for those in same-sex relationships.8
The Respect for Marriage Act (RFMA) was passed by the U.S. Congress and signed into law by President Biden on Dec. 13, 2022. This law officially repeals DOMA and requires all states and the federal government to recognize same-sex marriages performed in any U.S. state or territory.9
If the U.S. Supreme Court were to overturn the 2015 marriage equality decision, individual state laws ensuring or banning same-sex marriage would again be in effect. However, the RFMA ensures that all states continue to recognize same-sex marriages performed in any U.S. state or territory (even if that state itself bans same-sex marriage). While we do not yet have any studies or data regarding the effect of the RFMA on public health, we can expect positive effects by drawing on the previous evidence on the effect of marriage equality and its effect on the health and well-being of LGBTQ+ individuals. By establishing marriage equality in the United States, our government institutions are affirming the relationships and identities of those in same-sex relationships, with the potential effect of helping to destigmatize the LGBTQ+ community.
Since 2002, the American Academy of Pediatrics has recommended that pediatricians “support the right of every child and family to the financial, psychological, and legal security that results from having legally recognized parents who are committed to each other and to the welfare of their children,” acknowledging that “legislative initiatives assuring legal status equivalent to marriage for gay and lesbian partners … can also attend to providing security and permanence for the children of those partnerships.”10 While changes in legal marriage equality are likely to have a positive effect on those within the LGBTQ+ community, it should also be understood that this will not solve all of the psychosocial effects and resultant health disparities that these children face.
A recent scoping review highlights that, as the result of marriage equality progress, sexual minority adults have reported increased social acceptance and reduced stigma across individual, community, and societal levels, but that sexual minority stigma continues to persist across all levels.11
As pediatricians, we can continue to support LGBTQ+ patients and parents by providing care in a safe and affirming environment in which families understand and embrace the healthy development of gender identity and sexuality in an open and destigmatized manner. Delivering care using this approach in and of itself can be seen as advocacy to promote health and well-being within minoritized populations. Pediatricians are also encouraged to become engaged in local and national advocacy initiatives to have a broader effect in the fight for health equity in minority populations, including LGBTQ+ families and youth.
Pediatricians should work with their patients, families, and communities to advocate for structural change needed to address the social determinants of health for optimal growth and development.
Dr. Warus is an adolescent medicine physician who specializes in care for transgender and gender-nonconforming youth, and LGBTQ health for youth at Children’s Hospital of Los Angeles. He is an assistant professor of pediatrics at University of Southern California, Los Angeles.
Resources
Bright Futures – Promoting Healthy Development of Sexuality and Gender Identity (Implementation Tip Sheet): https://downloads.aap.org/AAP/PDF/BF_HealthySexualityGenderIdentity_Tipsheet.pdf
Bright Futures – Implementing Social Determinants of Health Into Health Supervision Visits (Implementation Tip Sheet): https://downloads.aap.org/AAP/PDF/Bright%20Futures/BF_IntegrateSDoH_Tipsheet.pdf?_ga=2.214227031.1330574154.1673910248-58875083.1673910248
American Academy of Pediatrics – Advocacy Website: https://www.aap.org/en/advocacy/
References
1. Hughes K et al. Lancet Public Health. 2017;2(8):e356-66.
2. Camero K and Javier JR. Pediatr Clin N Am. 2023;70:43-51.
3. Lund EM and Burgess CM. Prim Care Clin Office Pract. 2021;48:179-89.
4. Buffie WC. Am J Public Health. 2011;101(6):986-90.
5. Hatzenbuehler ML et al. Am J Public Health. 2010;100:452-9.
6. Raifman J et al. JAMA Pediatr. 2017;171(4):350-6.
7. Gonzales G and Blewett LA. Pediatrics. 2013;132(4):703-11.
8. Ogolsky BG et al. J Fam Psychol. 2019;33(4):422-32.
9. Library of Congress. H.R.8404 – 117th Congress (2021-2022): Respect for Marriage Act. 2022 Dec 13. www.congress.gov/bill/117th-congress/house-bill/8404/text.
10. Perrin EC and Committee on Psychosocial Aspects of Child and Family Health. Pediatrics. 2002;109(2):341-4.
11. Drabble LA et al. PLoS ONE. 2021;16(5):e0249125.
Childhood and adolescence are periods of life with rapid growth and development in which the psychosocial factors of one’s environment can have a profound effect on health. There is increasing evidence that adverse childhood experiences (ACEs) can have significant negative effects on long-term health with effects persisting into subsequent generations.1 Youth themselves, however, often do not have the voice, ability, or political power to advocate for safe and more supportive environments that are essential to their well-being. Thus, advocacy has been central to the profession of pediatrics since its inception, where providers can partner with their patients, families, and communities to push for changes in the environments in which youth live and grow.2
LGBTQ+ youth are known to be at increased risk for ACEs because of the stress that comes from being part of a minority group and the discrimination they experience by their families, communities, and society at large. These factors within their environments have been shown to be associated with increased rates of anxiety, depression, substance use, sexually transmitted infections, and homelessness.3 As with other health outcomes that have been linked to the social determinants of health, these disparities are not inevitable and could be greatly improved upon through advocacy and changes in the environments of LGBTQ+ youth.
Marriage equality (the recognition that same-sex couples have the same legal right to marry as opposite-sex couples) has been shown to be not only a political issue, but one that affects health. The debates surrounding marriage equality have contributed to minority stress by questioning the validity of same-sex relationships and assigning them less value relative to opposite-sex relationships.4 In 1996, the U.S. Congress passed the Defense of Marriage Act (DOMA), which federally defined marriage as being legally recognized only between opposite-sex couples.
Individual states then continued the marriage equality debate by passing individual state laws either allowing or prohibiting same-sex marriage. During this time, it was shown that, in states where same-sex marriage was legally prohibited, LGBTQ+ adults reported significantly higher rates of generalized anxiety disorder, alcohol use disorder, any mood disorder, and psychiatric comorbidity when compared with states without a legal ban on same-sex marriage.5
Using data from the Youth Risk Behavior Surveillance System, it was shown that state policies recognizing same-sex marriage were associated with a 7% relative reduction in suicide attempts reported by adolescent sexual minority students compared with before these policies.6 It was also shown that children with same-sex parents were overall less likely to have private health insurance, but this disparity was improved in states that legally recognized same-sex marriage and allowed second-parent adoptions.7
In 2013, the U.S. Supreme Court ruled that DOMA was unconstitutional, requiring the federal government to legally recognize same-sex marriages for the purposes of federal benefits. In 2015, the U.S. Supreme Court further ruled that same-sex couples are guaranteed the fundamental right to marry, requiring that all states issue marriage licenses to same-sex couples. These rulings were associated with a decrease in reported levels of stigma over time and increased reported levels of family support, particularly for those in same-sex relationships.8
The Respect for Marriage Act (RFMA) was passed by the U.S. Congress and signed into law by President Biden on Dec. 13, 2022. This law officially repeals DOMA and requires all states and the federal government to recognize same-sex marriages performed in any U.S. state or territory.9
If the U.S. Supreme Court were to overturn the 2015 marriage equality decision, individual state laws ensuring or banning same-sex marriage would again be in effect. However, the RFMA ensures that all states continue to recognize same-sex marriages performed in any U.S. state or territory (even if that state itself bans same-sex marriage). While we do not yet have any studies or data regarding the effect of the RFMA on public health, we can expect positive effects by drawing on the previous evidence on the effect of marriage equality and its effect on the health and well-being of LGBTQ+ individuals. By establishing marriage equality in the United States, our government institutions are affirming the relationships and identities of those in same-sex relationships, with the potential effect of helping to destigmatize the LGBTQ+ community.
Since 2002, the American Academy of Pediatrics has recommended that pediatricians “support the right of every child and family to the financial, psychological, and legal security that results from having legally recognized parents who are committed to each other and to the welfare of their children,” acknowledging that “legislative initiatives assuring legal status equivalent to marriage for gay and lesbian partners … can also attend to providing security and permanence for the children of those partnerships.”10 While changes in legal marriage equality are likely to have a positive effect on those within the LGBTQ+ community, it should also be understood that this will not solve all of the psychosocial effects and resultant health disparities that these children face.
A recent scoping review highlights that, as the result of marriage equality progress, sexual minority adults have reported increased social acceptance and reduced stigma across individual, community, and societal levels, but that sexual minority stigma continues to persist across all levels.11
As pediatricians, we can continue to support LGBTQ+ patients and parents by providing care in a safe and affirming environment in which families understand and embrace the healthy development of gender identity and sexuality in an open and destigmatized manner. Delivering care using this approach in and of itself can be seen as advocacy to promote health and well-being within minoritized populations. Pediatricians are also encouraged to become engaged in local and national advocacy initiatives to have a broader effect in the fight for health equity in minority populations, including LGBTQ+ families and youth.
Pediatricians should work with their patients, families, and communities to advocate for structural change needed to address the social determinants of health for optimal growth and development.
Dr. Warus is an adolescent medicine physician who specializes in care for transgender and gender-nonconforming youth, and LGBTQ health for youth at Children’s Hospital of Los Angeles. He is an assistant professor of pediatrics at University of Southern California, Los Angeles.
Resources
Bright Futures – Promoting Healthy Development of Sexuality and Gender Identity (Implementation Tip Sheet): https://downloads.aap.org/AAP/PDF/BF_HealthySexualityGenderIdentity_Tipsheet.pdf
Bright Futures – Implementing Social Determinants of Health Into Health Supervision Visits (Implementation Tip Sheet): https://downloads.aap.org/AAP/PDF/Bright%20Futures/BF_IntegrateSDoH_Tipsheet.pdf?_ga=2.214227031.1330574154.1673910248-58875083.1673910248
American Academy of Pediatrics – Advocacy Website: https://www.aap.org/en/advocacy/
References
1. Hughes K et al. Lancet Public Health. 2017;2(8):e356-66.
2. Camero K and Javier JR. Pediatr Clin N Am. 2023;70:43-51.
3. Lund EM and Burgess CM. Prim Care Clin Office Pract. 2021;48:179-89.
4. Buffie WC. Am J Public Health. 2011;101(6):986-90.
5. Hatzenbuehler ML et al. Am J Public Health. 2010;100:452-9.
6. Raifman J et al. JAMA Pediatr. 2017;171(4):350-6.
7. Gonzales G and Blewett LA. Pediatrics. 2013;132(4):703-11.
8. Ogolsky BG et al. J Fam Psychol. 2019;33(4):422-32.
9. Library of Congress. H.R.8404 – 117th Congress (2021-2022): Respect for Marriage Act. 2022 Dec 13. www.congress.gov/bill/117th-congress/house-bill/8404/text.
10. Perrin EC and Committee on Psychosocial Aspects of Child and Family Health. Pediatrics. 2002;109(2):341-4.
11. Drabble LA et al. PLoS ONE. 2021;16(5):e0249125.
Childhood and adolescence are periods of life with rapid growth and development in which the psychosocial factors of one’s environment can have a profound effect on health. There is increasing evidence that adverse childhood experiences (ACEs) can have significant negative effects on long-term health with effects persisting into subsequent generations.1 Youth themselves, however, often do not have the voice, ability, or political power to advocate for safe and more supportive environments that are essential to their well-being. Thus, advocacy has been central to the profession of pediatrics since its inception, where providers can partner with their patients, families, and communities to push for changes in the environments in which youth live and grow.2
LGBTQ+ youth are known to be at increased risk for ACEs because of the stress that comes from being part of a minority group and the discrimination they experience by their families, communities, and society at large. These factors within their environments have been shown to be associated with increased rates of anxiety, depression, substance use, sexually transmitted infections, and homelessness.3 As with other health outcomes that have been linked to the social determinants of health, these disparities are not inevitable and could be greatly improved upon through advocacy and changes in the environments of LGBTQ+ youth.
Marriage equality (the recognition that same-sex couples have the same legal right to marry as opposite-sex couples) has been shown to be not only a political issue, but one that affects health. The debates surrounding marriage equality have contributed to minority stress by questioning the validity of same-sex relationships and assigning them less value relative to opposite-sex relationships.4 In 1996, the U.S. Congress passed the Defense of Marriage Act (DOMA), which federally defined marriage as being legally recognized only between opposite-sex couples.
Individual states then continued the marriage equality debate by passing individual state laws either allowing or prohibiting same-sex marriage. During this time, it was shown that, in states where same-sex marriage was legally prohibited, LGBTQ+ adults reported significantly higher rates of generalized anxiety disorder, alcohol use disorder, any mood disorder, and psychiatric comorbidity when compared with states without a legal ban on same-sex marriage.5
Using data from the Youth Risk Behavior Surveillance System, it was shown that state policies recognizing same-sex marriage were associated with a 7% relative reduction in suicide attempts reported by adolescent sexual minority students compared with before these policies.6 It was also shown that children with same-sex parents were overall less likely to have private health insurance, but this disparity was improved in states that legally recognized same-sex marriage and allowed second-parent adoptions.7
In 2013, the U.S. Supreme Court ruled that DOMA was unconstitutional, requiring the federal government to legally recognize same-sex marriages for the purposes of federal benefits. In 2015, the U.S. Supreme Court further ruled that same-sex couples are guaranteed the fundamental right to marry, requiring that all states issue marriage licenses to same-sex couples. These rulings were associated with a decrease in reported levels of stigma over time and increased reported levels of family support, particularly for those in same-sex relationships.8
The Respect for Marriage Act (RFMA) was passed by the U.S. Congress and signed into law by President Biden on Dec. 13, 2022. This law officially repeals DOMA and requires all states and the federal government to recognize same-sex marriages performed in any U.S. state or territory.9
If the U.S. Supreme Court were to overturn the 2015 marriage equality decision, individual state laws ensuring or banning same-sex marriage would again be in effect. However, the RFMA ensures that all states continue to recognize same-sex marriages performed in any U.S. state or territory (even if that state itself bans same-sex marriage). While we do not yet have any studies or data regarding the effect of the RFMA on public health, we can expect positive effects by drawing on the previous evidence on the effect of marriage equality and its effect on the health and well-being of LGBTQ+ individuals. By establishing marriage equality in the United States, our government institutions are affirming the relationships and identities of those in same-sex relationships, with the potential effect of helping to destigmatize the LGBTQ+ community.
Since 2002, the American Academy of Pediatrics has recommended that pediatricians “support the right of every child and family to the financial, psychological, and legal security that results from having legally recognized parents who are committed to each other and to the welfare of their children,” acknowledging that “legislative initiatives assuring legal status equivalent to marriage for gay and lesbian partners … can also attend to providing security and permanence for the children of those partnerships.”10 While changes in legal marriage equality are likely to have a positive effect on those within the LGBTQ+ community, it should also be understood that this will not solve all of the psychosocial effects and resultant health disparities that these children face.
A recent scoping review highlights that, as the result of marriage equality progress, sexual minority adults have reported increased social acceptance and reduced stigma across individual, community, and societal levels, but that sexual minority stigma continues to persist across all levels.11
As pediatricians, we can continue to support LGBTQ+ patients and parents by providing care in a safe and affirming environment in which families understand and embrace the healthy development of gender identity and sexuality in an open and destigmatized manner. Delivering care using this approach in and of itself can be seen as advocacy to promote health and well-being within minoritized populations. Pediatricians are also encouraged to become engaged in local and national advocacy initiatives to have a broader effect in the fight for health equity in minority populations, including LGBTQ+ families and youth.
Pediatricians should work with their patients, families, and communities to advocate for structural change needed to address the social determinants of health for optimal growth and development.
Dr. Warus is an adolescent medicine physician who specializes in care for transgender and gender-nonconforming youth, and LGBTQ health for youth at Children’s Hospital of Los Angeles. He is an assistant professor of pediatrics at University of Southern California, Los Angeles.
Resources
Bright Futures – Promoting Healthy Development of Sexuality and Gender Identity (Implementation Tip Sheet): https://downloads.aap.org/AAP/PDF/BF_HealthySexualityGenderIdentity_Tipsheet.pdf
Bright Futures – Implementing Social Determinants of Health Into Health Supervision Visits (Implementation Tip Sheet): https://downloads.aap.org/AAP/PDF/Bright%20Futures/BF_IntegrateSDoH_Tipsheet.pdf?_ga=2.214227031.1330574154.1673910248-58875083.1673910248
American Academy of Pediatrics – Advocacy Website: https://www.aap.org/en/advocacy/
References
1. Hughes K et al. Lancet Public Health. 2017;2(8):e356-66.
2. Camero K and Javier JR. Pediatr Clin N Am. 2023;70:43-51.
3. Lund EM and Burgess CM. Prim Care Clin Office Pract. 2021;48:179-89.
4. Buffie WC. Am J Public Health. 2011;101(6):986-90.
5. Hatzenbuehler ML et al. Am J Public Health. 2010;100:452-9.
6. Raifman J et al. JAMA Pediatr. 2017;171(4):350-6.
7. Gonzales G and Blewett LA. Pediatrics. 2013;132(4):703-11.
8. Ogolsky BG et al. J Fam Psychol. 2019;33(4):422-32.
9. Library of Congress. H.R.8404 – 117th Congress (2021-2022): Respect for Marriage Act. 2022 Dec 13. www.congress.gov/bill/117th-congress/house-bill/8404/text.
10. Perrin EC and Committee on Psychosocial Aspects of Child and Family Health. Pediatrics. 2002;109(2):341-4.
11. Drabble LA et al. PLoS ONE. 2021;16(5):e0249125.
Can 6 minutes of intense cycling put the brakes on Alzheimer’s?
new research suggests.
In a small study of healthy adults, 6 minutes of high-intensity cycling increased circulating levels of brain-derived neurotrophic factor (BDNF) to a significantly greater extent than prolonged light cycling or fasting.
However, the data do not suggest that 6 minutes of high-intensity exercise “wards off dementia,” cautioned lead investigator Travis Gibbons, MSc, PhD candidate in environmental physiology at the University of Otago (New Zealand), Dunedin, and now postdoctoral fellow at the University of British Columbia – Okanagan, Kelowna.
“Like all science, this is just a small piece that supports a potential mechanistic role for how exercise might improve brain health,” Dr. Gibbons told this news organization.
The findings were published online in the Journal of Physiology.
Targeting BDNF
Both intermittent fasting and exercise have previously been shown to have potent neuroprotective effects; and an acute upregulation of BDNF appears to be a common mechanistic link.
To tease apart the influence of fasting and exercise on BDNF production, Dr. Gibbons and colleagues studied 12 aerobically fit, healthy men (n = 6) and women (n = 6) aged 20-40 years.
In a study that employed a repeated-measures crossover design, they assessed circulating BDNF levels after a 20-hour fast, prolonged (90-min) light cycling, short (6-min) high-intensity cycling, and combined fasting and exercise.
Six minutes of high-intensity exercise appeared to be the most efficient way to increase BDNF.
Fasting for 20 hours led to a ninefold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest or during exercise.
Six minutes of high-intensity exercise increased every metric of circulating BDNF four to five times more than prolonged low-intensity exercise.
In addition, the increase in plasma-derived BDNF correlated with a sixfold increase in circulating lactate irrespective of feeding or fasting state.
Lactate delivery?
“My leading theory is that, during and following intense exercise, lactate produced by muscles is delivered and consumed by the brain,” Dr. Gibbons noted.
“It takes high-intensity exercise to provoke this ‘cerebral substrate switch’ from glucose to lactate. Critically, this cerebral substrate switch has been shown to contribute to the early processes that upregulate BDNF production in the brain,” he said.
However, “Whether this translates to ‘warding off dementia’ is not clear,” Dr. Gibbons added.
The study also suggests that increases in plasma volume and platelet concentration appear to play a role in concentrating BDNF in the circulation during exercise.
The investigators note that BDNF and other neurotrophic-based pharmaceutical therapies have shown “great promise” in slowing and even arresting neurodegenerative processes in animals, but attempts to harness the protective power of BDNF in human neurodegeneration have thus far failed.
“Whether episodically upregulating BDNF production with intense exercise is an effective strategy to curb age-related cognitive decline in humans is unknown, but animal models indicate that it is and that BDNF plays a primary role,” the researchers write.
Funding for the study was provided by the Healthcare Otago Charitable Trust. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
In a small study of healthy adults, 6 minutes of high-intensity cycling increased circulating levels of brain-derived neurotrophic factor (BDNF) to a significantly greater extent than prolonged light cycling or fasting.
However, the data do not suggest that 6 minutes of high-intensity exercise “wards off dementia,” cautioned lead investigator Travis Gibbons, MSc, PhD candidate in environmental physiology at the University of Otago (New Zealand), Dunedin, and now postdoctoral fellow at the University of British Columbia – Okanagan, Kelowna.
“Like all science, this is just a small piece that supports a potential mechanistic role for how exercise might improve brain health,” Dr. Gibbons told this news organization.
The findings were published online in the Journal of Physiology.
Targeting BDNF
Both intermittent fasting and exercise have previously been shown to have potent neuroprotective effects; and an acute upregulation of BDNF appears to be a common mechanistic link.
To tease apart the influence of fasting and exercise on BDNF production, Dr. Gibbons and colleagues studied 12 aerobically fit, healthy men (n = 6) and women (n = 6) aged 20-40 years.
In a study that employed a repeated-measures crossover design, they assessed circulating BDNF levels after a 20-hour fast, prolonged (90-min) light cycling, short (6-min) high-intensity cycling, and combined fasting and exercise.
Six minutes of high-intensity exercise appeared to be the most efficient way to increase BDNF.
Fasting for 20 hours led to a ninefold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest or during exercise.
Six minutes of high-intensity exercise increased every metric of circulating BDNF four to five times more than prolonged low-intensity exercise.
In addition, the increase in plasma-derived BDNF correlated with a sixfold increase in circulating lactate irrespective of feeding or fasting state.
Lactate delivery?
“My leading theory is that, during and following intense exercise, lactate produced by muscles is delivered and consumed by the brain,” Dr. Gibbons noted.
“It takes high-intensity exercise to provoke this ‘cerebral substrate switch’ from glucose to lactate. Critically, this cerebral substrate switch has been shown to contribute to the early processes that upregulate BDNF production in the brain,” he said.
However, “Whether this translates to ‘warding off dementia’ is not clear,” Dr. Gibbons added.
The study also suggests that increases in plasma volume and platelet concentration appear to play a role in concentrating BDNF in the circulation during exercise.
The investigators note that BDNF and other neurotrophic-based pharmaceutical therapies have shown “great promise” in slowing and even arresting neurodegenerative processes in animals, but attempts to harness the protective power of BDNF in human neurodegeneration have thus far failed.
“Whether episodically upregulating BDNF production with intense exercise is an effective strategy to curb age-related cognitive decline in humans is unknown, but animal models indicate that it is and that BDNF plays a primary role,” the researchers write.
Funding for the study was provided by the Healthcare Otago Charitable Trust. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
In a small study of healthy adults, 6 minutes of high-intensity cycling increased circulating levels of brain-derived neurotrophic factor (BDNF) to a significantly greater extent than prolonged light cycling or fasting.
However, the data do not suggest that 6 minutes of high-intensity exercise “wards off dementia,” cautioned lead investigator Travis Gibbons, MSc, PhD candidate in environmental physiology at the University of Otago (New Zealand), Dunedin, and now postdoctoral fellow at the University of British Columbia – Okanagan, Kelowna.
“Like all science, this is just a small piece that supports a potential mechanistic role for how exercise might improve brain health,” Dr. Gibbons told this news organization.
The findings were published online in the Journal of Physiology.
Targeting BDNF
Both intermittent fasting and exercise have previously been shown to have potent neuroprotective effects; and an acute upregulation of BDNF appears to be a common mechanistic link.
To tease apart the influence of fasting and exercise on BDNF production, Dr. Gibbons and colleagues studied 12 aerobically fit, healthy men (n = 6) and women (n = 6) aged 20-40 years.
In a study that employed a repeated-measures crossover design, they assessed circulating BDNF levels after a 20-hour fast, prolonged (90-min) light cycling, short (6-min) high-intensity cycling, and combined fasting and exercise.
Six minutes of high-intensity exercise appeared to be the most efficient way to increase BDNF.
Fasting for 20 hours led to a ninefold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest or during exercise.
Six minutes of high-intensity exercise increased every metric of circulating BDNF four to five times more than prolonged low-intensity exercise.
In addition, the increase in plasma-derived BDNF correlated with a sixfold increase in circulating lactate irrespective of feeding or fasting state.
Lactate delivery?
“My leading theory is that, during and following intense exercise, lactate produced by muscles is delivered and consumed by the brain,” Dr. Gibbons noted.
“It takes high-intensity exercise to provoke this ‘cerebral substrate switch’ from glucose to lactate. Critically, this cerebral substrate switch has been shown to contribute to the early processes that upregulate BDNF production in the brain,” he said.
However, “Whether this translates to ‘warding off dementia’ is not clear,” Dr. Gibbons added.
The study also suggests that increases in plasma volume and platelet concentration appear to play a role in concentrating BDNF in the circulation during exercise.
The investigators note that BDNF and other neurotrophic-based pharmaceutical therapies have shown “great promise” in slowing and even arresting neurodegenerative processes in animals, but attempts to harness the protective power of BDNF in human neurodegeneration have thus far failed.
“Whether episodically upregulating BDNF production with intense exercise is an effective strategy to curb age-related cognitive decline in humans is unknown, but animal models indicate that it is and that BDNF plays a primary role,” the researchers write.
Funding for the study was provided by the Healthcare Otago Charitable Trust. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF PHYSIOLOGY
Low serum LDH shows potential as depression biomarker
The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.
Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.
“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.
In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).
The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.
The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.
In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.
Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.
The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.
The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.
The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.
Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.
“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.
In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).
The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.
The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.
In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.
Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.
The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.
The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.
The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.
Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.
“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.
In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).
The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.
The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.
In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.
Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.
The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.
The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.
FROM GENERAL HOSPITAL PSYCHIATRY
Mood disorder? Assessment in primary care
The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?
Case
Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.
Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.
Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.
To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
Case discussion
First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.
Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.
Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3
In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
Case, continued
When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5
With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.
At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
Case discussion, continued
The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9
Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.
Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.
A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.
There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13
Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14
You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
Case, continued
Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16
You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17
While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.
Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
References
1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.
2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.
4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.
5. The CRAFFT tool.
6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).
7. Child Mania Rating Scale, Parent Version (CMRS-P).
8. https://www.moodtracker.com.
9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.
10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.
11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.
13. www.cabsresearch.pitt.edu/bpriskcalculator/.
14. Parent Version of the Young Mania Rating Scale (PYMRS).
15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.
16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.
17. https://www.ipsrt.org/.
The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?
Case
Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.
Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.
Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.
To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
Case discussion
First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.
Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.
Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3
In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
Case, continued
When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5
With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.
At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
Case discussion, continued
The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9
Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.
Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.
A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.
There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13
Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14
You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
Case, continued
Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16
You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17
While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.
Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
References
1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.
2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.
4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.
5. The CRAFFT tool.
6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).
7. Child Mania Rating Scale, Parent Version (CMRS-P).
8. https://www.moodtracker.com.
9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.
10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.
11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.
13. www.cabsresearch.pitt.edu/bpriskcalculator/.
14. Parent Version of the Young Mania Rating Scale (PYMRS).
15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.
16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.
17. https://www.ipsrt.org/.
The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?
Case
Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.
Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.
Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.
To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
Case discussion
First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.
Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.
Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3
In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
Case, continued
When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5
With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.
At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
Case discussion, continued
The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9
Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.
Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.
A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.
There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13
Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14
You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
Case, continued
Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16
You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17
While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.
Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
References
1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.
2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.
4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.
5. The CRAFFT tool.
6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).
7. Child Mania Rating Scale, Parent Version (CMRS-P).
8. https://www.moodtracker.com.
9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.
10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.
11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.
13. www.cabsresearch.pitt.edu/bpriskcalculator/.
14. Parent Version of the Young Mania Rating Scale (PYMRS).
15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.
16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.
17. https://www.ipsrt.org/.
The pediatrician’s office may be the first setting for a child to present with mood symptoms.
Self-management app may boost quality of life
In a randomized clinical trial of usual care plus the experimental smartphone-based intervention known as LiveWell vs. usual care alone, participants in the smartphone group who were categorized as low-risk or in asymptomatic recovery at baseline also showed reduced manic symptom severity.
The results suggest that “apps for individuals with bipolar disorder will likely be useful for some people in managing medication use, sleep duration, routine, and monitoring for and managing signs and symptoms” of the disorder, coinvestigator Evan H. Goulding, MD, PhD, assistant professor of psychiatry and behavioral sciences, Northwestern University, Chicago, told this news organization.
Use of the app may also “lead to decreased recurrence of mood episodes, impact overall depressive and manic symptom levels, and improve some aspects of quality of life,” Dr. Goulding added.
The findings were published online in JAMA Psychiatry.
Daily check-ins
The researchers randomly assigned 205 patients with BD to receive either usual care (n = 81; 56% women; mean age, 39 years) or usual care plus the smartphone-based self-management intervention LiveWell (n = 124; 65% women; mean age, 43 years) between March 2017 and April 2020. To be included, participants could not be experiencing a current mood episode or suicidal ideation.
The smartphone intervention included a daily check-in to monitor medication adherence, sleep, and wellness levels; coach visits to support adherence to the app; six phone calls over 16 weeks; and support from mental health professionals whenever needed. Participants in this group were asked to engage their mental health providers in the intervention as well.
Each participant in the control group had a visit with a coach who facilitated self-management support.
Investigators assessed all participants every 8 weeks until week 48 to gather information on mood symptoms and severity over the past 2 weeks and on quality of life.
The patients were also stratified into high- and low-risk relapse groups. The low-risk group was in asymptomatic recovery, meaning that they experienced two or fewer moderate symptoms of mania or depression in the previous 8 weeks. In addition, they had no moderate symptoms of mania or depression at study enrollment.
Patients in the high-risk group were recovering from an episode of mania or depression. They also had two or fewer moderate symptoms, but for 8 weeks or less.
Low-risk group fares better
Results showed that the smartphone intervention was significantly associated with a reduction in depressive symptoms vs. usual care (P = .02), as well as improvement in one aspect of the World Health Organization Quality of Life Assessment that measures social relationships (P = .02).
When the investigators stratified participants into risk groups, they found that for those in the low-risk group the smartphone-based intervention was associated with lower episode-relapse rates, lower mean percentage time symptomatic, and decreased manic symptom severity.
Mean estimated relapse rates by 48 weeks for the low-risk group were 12% for those in the intervention group and 37.2% for those in the control group. No differences were noted for the high-risk group.
Low-risk patients in the intervention group also had lower mean percentage-time symptomatic (17.9%) than those in the control group (26.1%) (Cohen d = .31).
“Our results are consistent with literature emphasizing the identification and facilitation of management plans for early warning signs of mood episodes and using these plans as an important self-management technique for avoiding relapse,” Dr. Goulding said.
Study limitations included low engagement by mental health professionals and low data generalizability to other populations, as the sample was mostly White (84% of the app group and 81% of the control group).
“There is a fairly large literature on risk factors, longitudinal trajectories, and stages of diseases that suggest we should already be able to predict relapse risk for individuals,” Dr. Goulding said.
“However, moving from overall risk to individual risk is trickier and will require larger datasets with longer follow-up to better understand what types of help should be delivered when and to whom,” he added.
‘Requires commitment’
John Torous, MD, director of the division of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, noted that mental health apps such as LiveWell require “time and energy devoted by both the patient and their clinician for maximal efficacy, which requires commitment from and training for both parties as well.
“But with such an investment in people, there is good evidence apps can help people with bipolar disorder even during the more severe periods of the illness,” added Dr. Torous, who was not involved with the research.
The study was funded by the National Institute of Mental Health.
Dr. Goulding reports having received honoraria from Otsuka. Dr. Torous has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a randomized clinical trial of usual care plus the experimental smartphone-based intervention known as LiveWell vs. usual care alone, participants in the smartphone group who were categorized as low-risk or in asymptomatic recovery at baseline also showed reduced manic symptom severity.
The results suggest that “apps for individuals with bipolar disorder will likely be useful for some people in managing medication use, sleep duration, routine, and monitoring for and managing signs and symptoms” of the disorder, coinvestigator Evan H. Goulding, MD, PhD, assistant professor of psychiatry and behavioral sciences, Northwestern University, Chicago, told this news organization.
Use of the app may also “lead to decreased recurrence of mood episodes, impact overall depressive and manic symptom levels, and improve some aspects of quality of life,” Dr. Goulding added.
The findings were published online in JAMA Psychiatry.
Daily check-ins
The researchers randomly assigned 205 patients with BD to receive either usual care (n = 81; 56% women; mean age, 39 years) or usual care plus the smartphone-based self-management intervention LiveWell (n = 124; 65% women; mean age, 43 years) between March 2017 and April 2020. To be included, participants could not be experiencing a current mood episode or suicidal ideation.
The smartphone intervention included a daily check-in to monitor medication adherence, sleep, and wellness levels; coach visits to support adherence to the app; six phone calls over 16 weeks; and support from mental health professionals whenever needed. Participants in this group were asked to engage their mental health providers in the intervention as well.
Each participant in the control group had a visit with a coach who facilitated self-management support.
Investigators assessed all participants every 8 weeks until week 48 to gather information on mood symptoms and severity over the past 2 weeks and on quality of life.
The patients were also stratified into high- and low-risk relapse groups. The low-risk group was in asymptomatic recovery, meaning that they experienced two or fewer moderate symptoms of mania or depression in the previous 8 weeks. In addition, they had no moderate symptoms of mania or depression at study enrollment.
Patients in the high-risk group were recovering from an episode of mania or depression. They also had two or fewer moderate symptoms, but for 8 weeks or less.
Low-risk group fares better
Results showed that the smartphone intervention was significantly associated with a reduction in depressive symptoms vs. usual care (P = .02), as well as improvement in one aspect of the World Health Organization Quality of Life Assessment that measures social relationships (P = .02).
When the investigators stratified participants into risk groups, they found that for those in the low-risk group the smartphone-based intervention was associated with lower episode-relapse rates, lower mean percentage time symptomatic, and decreased manic symptom severity.
Mean estimated relapse rates by 48 weeks for the low-risk group were 12% for those in the intervention group and 37.2% for those in the control group. No differences were noted for the high-risk group.
Low-risk patients in the intervention group also had lower mean percentage-time symptomatic (17.9%) than those in the control group (26.1%) (Cohen d = .31).
“Our results are consistent with literature emphasizing the identification and facilitation of management plans for early warning signs of mood episodes and using these plans as an important self-management technique for avoiding relapse,” Dr. Goulding said.
Study limitations included low engagement by mental health professionals and low data generalizability to other populations, as the sample was mostly White (84% of the app group and 81% of the control group).
“There is a fairly large literature on risk factors, longitudinal trajectories, and stages of diseases that suggest we should already be able to predict relapse risk for individuals,” Dr. Goulding said.
“However, moving from overall risk to individual risk is trickier and will require larger datasets with longer follow-up to better understand what types of help should be delivered when and to whom,” he added.
‘Requires commitment’
John Torous, MD, director of the division of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, noted that mental health apps such as LiveWell require “time and energy devoted by both the patient and their clinician for maximal efficacy, which requires commitment from and training for both parties as well.
“But with such an investment in people, there is good evidence apps can help people with bipolar disorder even during the more severe periods of the illness,” added Dr. Torous, who was not involved with the research.
The study was funded by the National Institute of Mental Health.
Dr. Goulding reports having received honoraria from Otsuka. Dr. Torous has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a randomized clinical trial of usual care plus the experimental smartphone-based intervention known as LiveWell vs. usual care alone, participants in the smartphone group who were categorized as low-risk or in asymptomatic recovery at baseline also showed reduced manic symptom severity.
The results suggest that “apps for individuals with bipolar disorder will likely be useful for some people in managing medication use, sleep duration, routine, and monitoring for and managing signs and symptoms” of the disorder, coinvestigator Evan H. Goulding, MD, PhD, assistant professor of psychiatry and behavioral sciences, Northwestern University, Chicago, told this news organization.
Use of the app may also “lead to decreased recurrence of mood episodes, impact overall depressive and manic symptom levels, and improve some aspects of quality of life,” Dr. Goulding added.
The findings were published online in JAMA Psychiatry.
Daily check-ins
The researchers randomly assigned 205 patients with BD to receive either usual care (n = 81; 56% women; mean age, 39 years) or usual care plus the smartphone-based self-management intervention LiveWell (n = 124; 65% women; mean age, 43 years) between March 2017 and April 2020. To be included, participants could not be experiencing a current mood episode or suicidal ideation.
The smartphone intervention included a daily check-in to monitor medication adherence, sleep, and wellness levels; coach visits to support adherence to the app; six phone calls over 16 weeks; and support from mental health professionals whenever needed. Participants in this group were asked to engage their mental health providers in the intervention as well.
Each participant in the control group had a visit with a coach who facilitated self-management support.
Investigators assessed all participants every 8 weeks until week 48 to gather information on mood symptoms and severity over the past 2 weeks and on quality of life.
The patients were also stratified into high- and low-risk relapse groups. The low-risk group was in asymptomatic recovery, meaning that they experienced two or fewer moderate symptoms of mania or depression in the previous 8 weeks. In addition, they had no moderate symptoms of mania or depression at study enrollment.
Patients in the high-risk group were recovering from an episode of mania or depression. They also had two or fewer moderate symptoms, but for 8 weeks or less.
Low-risk group fares better
Results showed that the smartphone intervention was significantly associated with a reduction in depressive symptoms vs. usual care (P = .02), as well as improvement in one aspect of the World Health Organization Quality of Life Assessment that measures social relationships (P = .02).
When the investigators stratified participants into risk groups, they found that for those in the low-risk group the smartphone-based intervention was associated with lower episode-relapse rates, lower mean percentage time symptomatic, and decreased manic symptom severity.
Mean estimated relapse rates by 48 weeks for the low-risk group were 12% for those in the intervention group and 37.2% for those in the control group. No differences were noted for the high-risk group.
Low-risk patients in the intervention group also had lower mean percentage-time symptomatic (17.9%) than those in the control group (26.1%) (Cohen d = .31).
“Our results are consistent with literature emphasizing the identification and facilitation of management plans for early warning signs of mood episodes and using these plans as an important self-management technique for avoiding relapse,” Dr. Goulding said.
Study limitations included low engagement by mental health professionals and low data generalizability to other populations, as the sample was mostly White (84% of the app group and 81% of the control group).
“There is a fairly large literature on risk factors, longitudinal trajectories, and stages of diseases that suggest we should already be able to predict relapse risk for individuals,” Dr. Goulding said.
“However, moving from overall risk to individual risk is trickier and will require larger datasets with longer follow-up to better understand what types of help should be delivered when and to whom,” he added.
‘Requires commitment’
John Torous, MD, director of the division of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, noted that mental health apps such as LiveWell require “time and energy devoted by both the patient and their clinician for maximal efficacy, which requires commitment from and training for both parties as well.
“But with such an investment in people, there is good evidence apps can help people with bipolar disorder even during the more severe periods of the illness,” added Dr. Torous, who was not involved with the research.
The study was funded by the National Institute of Mental Health.
Dr. Goulding reports having received honoraria from Otsuka. Dr. Torous has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY