Mental Health

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Brain imaging combined with artificial intelligence has identified six distinct “biotypes” of depression and anxiety that may lead to more personalized and effective treatment.

This research has “immediate clinical implications,” study investigator Leanne Williams, PhD, director of the Stanford Medicine Center for Precision Mental Health and Wellness, told this news organization.

“At Stanford, we have started translating the imaging technology into use in a new precision mental health clinic. The technology is being actively developed for wider use in clinical settings, and we hope to make it accessible to more clinicians and patients,” Dr. Williams said.

The study was published online in Nature Medicine.

 

No More Trial and Error?

Depression is a highly heterogeneous disease, with individual patients having different symptoms and treatment responses. About 30% of patients with major depression are resistant to treatment, and about half of patients with generalized anxiety disorder do not respond to first-line treatment.

“The dominant ‘one-size-fits-all’ diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive, and frustrating, with 30%-40% of patients not achieving remission after trying one treatment,” the authors noted.

“The goal of our work is figuring out how we can get it right the first time,” Dr. Williams said in a news release, and that requires a better understanding of the neurobiology of depression.

To that end, 801 adults diagnosed with depression and anxiety underwent functional MRI to measure brain activity at rest and when engaged in tasks designed to test cognitive and emotional functioning.

Researchers probed six brain circuits previously associated with depression: the default mode circuit, salience circuit, attention circuit, negative affect circuit, positive affect circuit, and the cognitive control circuit.

Using a machine learning technique known as cluster analysis to group the patients’ brain images, they identified six clinically distinct biotypes of depression and anxiety defined by specific profiles of dysfunction within both task-free and task-evoked brain circuits.

“Importantly for clinical translation, these biotypes predict response to different pharmacological and behavioral interventions,” investigators wrote.

For example, patients with a biotype characterized by overactivity in cognitive regions of the brain experienced the best response to the antidepressant venlafaxine, compared with patients with other biotypes.

Patients with a different biotype, characterized by higher at-rest levels of activity in three regions associated with depression and problem-solving, responded better to behavioral therapy.

In addition, those with a third biotype, who had lower levels of activity at rest in the brain circuit that controls attention, were less apt to see improvement of their symptoms with behavioral therapy than those with other biotypes. The various biotypes also correlated with differences in symptoms and task performance.

For example, individuals with overactive cognitive regions of the brain had higher levels of anhedonia than those with other biotypes, and they also performed worse on tasks measuring executive function. Those with the biotype that responded best to behavioral therapy also made errors on executive function tasks but performed well on cognitive tasks.
 

A Work in Progress

The findings provide a deeper understanding of the neurobiological underpinnings of depression and anxiety and could lead to improved diagnostic accuracy and more tailored treatment approaches, the researchers noted.

Naming the biotypes is a work in progress, Dr. Williams said.

“We have thought a lot about the naming. In the Nature Medicine paper, we use a technical convention to name the biotypes based on which brain circuit problems define each of them,” she explained.

“For example, the first biotype is called DC+SC+AC+ because it is defined by connectivity increases [C+] on three resting circuits — default mode [D], salience [S], and frontoparietal attention [A]. We are working with collaborators to generate biotype names that could be convergent across findings and labs. In the near future, we anticipate generating more descriptive medical names that clinicians could refer to alongside the technical names,” Dr. Williams said.

Commenting on the research for this news organization, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai, New York, called it “super exciting.”

“The work from this research group is an excellent example of where precision psychiatry research is right now, particularly with regard to the use of brain imaging to personalize treatment, and this paper gives us a glimpse of where we could be in the not-too-distant future,” Dr. Murrough said.

However, he cautioned that at this point, “we’re far from realizing the dream of precision psychiatry. We just don’t have robust evidence that brain imaging markers can really guide clinical decision-making currently.”

Funding for the study was provided by the National Institutes of Health and by Brain Resource Ltd. Dr. Williams declared US patent applications numbered 10/034,645 and 15/820,338: “Systems and methods for detecting complex networks in MRI data.” Dr. Murrough had no relevant disclosures.

A version of this article appeared on Medscape.com.

Brain imaging combined with artificial intelligence has identified six distinct “biotypes” of depression and anxiety that may lead to more personalized and effective treatment.

This research has “immediate clinical implications,” study investigator Leanne Williams, PhD, director of the Stanford Medicine Center for Precision Mental Health and Wellness, told this news organization.

“At Stanford, we have started translating the imaging technology into use in a new precision mental health clinic. The technology is being actively developed for wider use in clinical settings, and we hope to make it accessible to more clinicians and patients,” Dr. Williams said.

The study was published online in Nature Medicine.

 

No More Trial and Error?

Depression is a highly heterogeneous disease, with individual patients having different symptoms and treatment responses. About 30% of patients with major depression are resistant to treatment, and about half of patients with generalized anxiety disorder do not respond to first-line treatment.

“The dominant ‘one-size-fits-all’ diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive, and frustrating, with 30%-40% of patients not achieving remission after trying one treatment,” the authors noted.

“The goal of our work is figuring out how we can get it right the first time,” Dr. Williams said in a news release, and that requires a better understanding of the neurobiology of depression.

To that end, 801 adults diagnosed with depression and anxiety underwent functional MRI to measure brain activity at rest and when engaged in tasks designed to test cognitive and emotional functioning.

Researchers probed six brain circuits previously associated with depression: the default mode circuit, salience circuit, attention circuit, negative affect circuit, positive affect circuit, and the cognitive control circuit.

Using a machine learning technique known as cluster analysis to group the patients’ brain images, they identified six clinically distinct biotypes of depression and anxiety defined by specific profiles of dysfunction within both task-free and task-evoked brain circuits.

“Importantly for clinical translation, these biotypes predict response to different pharmacological and behavioral interventions,” investigators wrote.

For example, patients with a biotype characterized by overactivity in cognitive regions of the brain experienced the best response to the antidepressant venlafaxine, compared with patients with other biotypes.

Patients with a different biotype, characterized by higher at-rest levels of activity in three regions associated with depression and problem-solving, responded better to behavioral therapy.

In addition, those with a third biotype, who had lower levels of activity at rest in the brain circuit that controls attention, were less apt to see improvement of their symptoms with behavioral therapy than those with other biotypes. The various biotypes also correlated with differences in symptoms and task performance.

For example, individuals with overactive cognitive regions of the brain had higher levels of anhedonia than those with other biotypes, and they also performed worse on tasks measuring executive function. Those with the biotype that responded best to behavioral therapy also made errors on executive function tasks but performed well on cognitive tasks.
 

A Work in Progress

The findings provide a deeper understanding of the neurobiological underpinnings of depression and anxiety and could lead to improved diagnostic accuracy and more tailored treatment approaches, the researchers noted.

Naming the biotypes is a work in progress, Dr. Williams said.

“We have thought a lot about the naming. In the Nature Medicine paper, we use a technical convention to name the biotypes based on which brain circuit problems define each of them,” she explained.

“For example, the first biotype is called DC+SC+AC+ because it is defined by connectivity increases [C+] on three resting circuits — default mode [D], salience [S], and frontoparietal attention [A]. We are working with collaborators to generate biotype names that could be convergent across findings and labs. In the near future, we anticipate generating more descriptive medical names that clinicians could refer to alongside the technical names,” Dr. Williams said.

Commenting on the research for this news organization, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai, New York, called it “super exciting.”

“The work from this research group is an excellent example of where precision psychiatry research is right now, particularly with regard to the use of brain imaging to personalize treatment, and this paper gives us a glimpse of where we could be in the not-too-distant future,” Dr. Murrough said.

However, he cautioned that at this point, “we’re far from realizing the dream of precision psychiatry. We just don’t have robust evidence that brain imaging markers can really guide clinical decision-making currently.”

Funding for the study was provided by the National Institutes of Health and by Brain Resource Ltd. Dr. Williams declared US patent applications numbered 10/034,645 and 15/820,338: “Systems and methods for detecting complex networks in MRI data.” Dr. Murrough had no relevant disclosures.

A version of this article appeared on Medscape.com.

Brain imaging combined with artificial intelligence has identified six distinct “biotypes” of depression and anxiety that may lead to more personalized and effective treatment.

This research has “immediate clinical implications,” study investigator Leanne Williams, PhD, director of the Stanford Medicine Center for Precision Mental Health and Wellness, told this news organization.

“At Stanford, we have started translating the imaging technology into use in a new precision mental health clinic. The technology is being actively developed for wider use in clinical settings, and we hope to make it accessible to more clinicians and patients,” Dr. Williams said.

The study was published online in Nature Medicine.

 

No More Trial and Error?

Depression is a highly heterogeneous disease, with individual patients having different symptoms and treatment responses. About 30% of patients with major depression are resistant to treatment, and about half of patients with generalized anxiety disorder do not respond to first-line treatment.

“The dominant ‘one-size-fits-all’ diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive, and frustrating, with 30%-40% of patients not achieving remission after trying one treatment,” the authors noted.

“The goal of our work is figuring out how we can get it right the first time,” Dr. Williams said in a news release, and that requires a better understanding of the neurobiology of depression.

To that end, 801 adults diagnosed with depression and anxiety underwent functional MRI to measure brain activity at rest and when engaged in tasks designed to test cognitive and emotional functioning.

Researchers probed six brain circuits previously associated with depression: the default mode circuit, salience circuit, attention circuit, negative affect circuit, positive affect circuit, and the cognitive control circuit.

Using a machine learning technique known as cluster analysis to group the patients’ brain images, they identified six clinically distinct biotypes of depression and anxiety defined by specific profiles of dysfunction within both task-free and task-evoked brain circuits.

“Importantly for clinical translation, these biotypes predict response to different pharmacological and behavioral interventions,” investigators wrote.

For example, patients with a biotype characterized by overactivity in cognitive regions of the brain experienced the best response to the antidepressant venlafaxine, compared with patients with other biotypes.

Patients with a different biotype, characterized by higher at-rest levels of activity in three regions associated with depression and problem-solving, responded better to behavioral therapy.

In addition, those with a third biotype, who had lower levels of activity at rest in the brain circuit that controls attention, were less apt to see improvement of their symptoms with behavioral therapy than those with other biotypes. The various biotypes also correlated with differences in symptoms and task performance.

For example, individuals with overactive cognitive regions of the brain had higher levels of anhedonia than those with other biotypes, and they also performed worse on tasks measuring executive function. Those with the biotype that responded best to behavioral therapy also made errors on executive function tasks but performed well on cognitive tasks.
 

A Work in Progress

The findings provide a deeper understanding of the neurobiological underpinnings of depression and anxiety and could lead to improved diagnostic accuracy and more tailored treatment approaches, the researchers noted.

Naming the biotypes is a work in progress, Dr. Williams said.

“We have thought a lot about the naming. In the Nature Medicine paper, we use a technical convention to name the biotypes based on which brain circuit problems define each of them,” she explained.

“For example, the first biotype is called DC+SC+AC+ because it is defined by connectivity increases [C+] on three resting circuits — default mode [D], salience [S], and frontoparietal attention [A]. We are working with collaborators to generate biotype names that could be convergent across findings and labs. In the near future, we anticipate generating more descriptive medical names that clinicians could refer to alongside the technical names,” Dr. Williams said.

Commenting on the research for this news organization, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai, New York, called it “super exciting.”

“The work from this research group is an excellent example of where precision psychiatry research is right now, particularly with regard to the use of brain imaging to personalize treatment, and this paper gives us a glimpse of where we could be in the not-too-distant future,” Dr. Murrough said.

However, he cautioned that at this point, “we’re far from realizing the dream of precision psychiatry. We just don’t have robust evidence that brain imaging markers can really guide clinical decision-making currently.”

Funding for the study was provided by the National Institutes of Health and by Brain Resource Ltd. Dr. Williams declared US patent applications numbered 10/034,645 and 15/820,338: “Systems and methods for detecting complex networks in MRI data.” Dr. Murrough had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

Among the more unheralded examples of collateral damage of the COVID epidemic is chronic absenteeism. A recent NPR/Ipsos poll found that parents ranked chronic absenteeism last in a list of 12 school-related concerns. Only 5% listed it first.

This is surprising and concerning, given that prior to the pandemic the rate of chronic absenteeism nationwide was 15%, but during the 2021-22 school year this doubled to 30% and it has not declined. In fact, in some states the chronic absenteeism rate is 40%. In 2020 8 million students were chronically absent. This number is now over 14 million. Chronic absenteeism is a metric defined as a student absent for 15 days or more, which comes out to around 10% of the school year. Chronic absenteeism has been used as a predictor of the student dropout rate.

The initial contribution of the pandemic is easily explained, as parents were understandably concerned about sending their children into an environment that might cause disease, or at least bring the disease home to a more vulnerable family member. The reasons behind the trend’s persistence are a bit more complicated.

Family schedules initially disrupted by the pandemic have settled back into a pattern that may make it more difficult for a child to get to school. Day care and work schedules may have changed, but not yet readjusted to sync with the school schedule.

In the simplest terms, children and their families may have simply fallen out of the habit of going to school. For children (and maybe their parents) who had always struggled with an unresolved separation anxiety, the time at home — or at least not in school — came as a relief. Which, in turn, meant that any gains in dealing with the anxiety have been undone. The child who was already struggling academically or socially found being at home much less challenging. It’s not surprising that he/she might resist climbing back in the academic saddle.

It is very likely that a significant contributor to the persistent trend in chronic absenteeism is what social scientists call “norm erosion.” Not just children, but families may have developed an attitude that time spent in school just isn’t as valuable as they once believed, or were at least told that it was. There seems to be more parents questioning what their children are being taught in school. The home schooling movement existed before the pandemic. Its roots may be growing under the surface in the form of general skepticism about the importance of school in the bigger scheme of things. The home schooling movement was ready to blossom when the COVID pandemic triggered school closures. We hoped and dreamed that remote learning would be just as good as in-person school. We now realize that, in most cases, that was wishful thinking.

It feels as though a “Perfect Attendance Record” may have lost the cachet it once had. During the pandemic anyone claiming to have never missed a day at school lost that gold star. Did opening your computer every day to watch a remote learning session count for anything?

The threshold for allowing a child to stay home from school may be reaching a historic low. Families seem to regard the school schedule as a guideline that can easily be ignored when planning a vacation. Take little brother out of school to attend big brother’s lacrosse playoff game, not to worry if the youngster misses school days for a trip.

Who is responsible for reversing the trend? Teachers already know it is a serious problem. They view attendance as important. Maybe educators could make school more appealing. But to whom? Sounds like this message should be targeted at the parents. Would stiff penalties for parents whose children are chronically absent help? Would demanding a note from a physician after a certain number of absences help? It might. But, are pediatricians and educators ready to take on one more task in which parents have dropped the ball?

An unknown percentage of chronically absent children are missing school because of a previously unrecognized or inadequately treated mental health condition or learning disability. Involving physicians in a community’s response to chronic absenteeism may be the first step in getting a child back on track. If socioeconomic factors are contributing to a child’s truancy, the involvement of social service agencies may be the answer.

I have a friend who is often asked to address graduating classes at both the high school and college level. One of his standard pieces of advice, whether it be about school or a workplace you may not be in love with, is to at least “show up.” The family that treats school attendance as optional is likely to produce adults who take a similarly nonchalant attitude toward their employment opportunities — with unfortunate results.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Among the more unheralded examples of collateral damage of the COVID epidemic is chronic absenteeism. A recent NPR/Ipsos poll found that parents ranked chronic absenteeism last in a list of 12 school-related concerns. Only 5% listed it first.

This is surprising and concerning, given that prior to the pandemic the rate of chronic absenteeism nationwide was 15%, but during the 2021-22 school year this doubled to 30% and it has not declined. In fact, in some states the chronic absenteeism rate is 40%. In 2020 8 million students were chronically absent. This number is now over 14 million. Chronic absenteeism is a metric defined as a student absent for 15 days or more, which comes out to around 10% of the school year. Chronic absenteeism has been used as a predictor of the student dropout rate.

The initial contribution of the pandemic is easily explained, as parents were understandably concerned about sending their children into an environment that might cause disease, or at least bring the disease home to a more vulnerable family member. The reasons behind the trend’s persistence are a bit more complicated.

Family schedules initially disrupted by the pandemic have settled back into a pattern that may make it more difficult for a child to get to school. Day care and work schedules may have changed, but not yet readjusted to sync with the school schedule.

In the simplest terms, children and their families may have simply fallen out of the habit of going to school. For children (and maybe their parents) who had always struggled with an unresolved separation anxiety, the time at home — or at least not in school — came as a relief. Which, in turn, meant that any gains in dealing with the anxiety have been undone. The child who was already struggling academically or socially found being at home much less challenging. It’s not surprising that he/she might resist climbing back in the academic saddle.

It is very likely that a significant contributor to the persistent trend in chronic absenteeism is what social scientists call “norm erosion.” Not just children, but families may have developed an attitude that time spent in school just isn’t as valuable as they once believed, or were at least told that it was. There seems to be more parents questioning what their children are being taught in school. The home schooling movement existed before the pandemic. Its roots may be growing under the surface in the form of general skepticism about the importance of school in the bigger scheme of things. The home schooling movement was ready to blossom when the COVID pandemic triggered school closures. We hoped and dreamed that remote learning would be just as good as in-person school. We now realize that, in most cases, that was wishful thinking.

It feels as though a “Perfect Attendance Record” may have lost the cachet it once had. During the pandemic anyone claiming to have never missed a day at school lost that gold star. Did opening your computer every day to watch a remote learning session count for anything?

The threshold for allowing a child to stay home from school may be reaching a historic low. Families seem to regard the school schedule as a guideline that can easily be ignored when planning a vacation. Take little brother out of school to attend big brother’s lacrosse playoff game, not to worry if the youngster misses school days for a trip.

Who is responsible for reversing the trend? Teachers already know it is a serious problem. They view attendance as important. Maybe educators could make school more appealing. But to whom? Sounds like this message should be targeted at the parents. Would stiff penalties for parents whose children are chronically absent help? Would demanding a note from a physician after a certain number of absences help? It might. But, are pediatricians and educators ready to take on one more task in which parents have dropped the ball?

An unknown percentage of chronically absent children are missing school because of a previously unrecognized or inadequately treated mental health condition or learning disability. Involving physicians in a community’s response to chronic absenteeism may be the first step in getting a child back on track. If socioeconomic factors are contributing to a child’s truancy, the involvement of social service agencies may be the answer.

I have a friend who is often asked to address graduating classes at both the high school and college level. One of his standard pieces of advice, whether it be about school or a workplace you may not be in love with, is to at least “show up.” The family that treats school attendance as optional is likely to produce adults who take a similarly nonchalant attitude toward their employment opportunities — with unfortunate results.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Among the more unheralded examples of collateral damage of the COVID epidemic is chronic absenteeism. A recent NPR/Ipsos poll found that parents ranked chronic absenteeism last in a list of 12 school-related concerns. Only 5% listed it first.

This is surprising and concerning, given that prior to the pandemic the rate of chronic absenteeism nationwide was 15%, but during the 2021-22 school year this doubled to 30% and it has not declined. In fact, in some states the chronic absenteeism rate is 40%. In 2020 8 million students were chronically absent. This number is now over 14 million. Chronic absenteeism is a metric defined as a student absent for 15 days or more, which comes out to around 10% of the school year. Chronic absenteeism has been used as a predictor of the student dropout rate.

The initial contribution of the pandemic is easily explained, as parents were understandably concerned about sending their children into an environment that might cause disease, or at least bring the disease home to a more vulnerable family member. The reasons behind the trend’s persistence are a bit more complicated.

Family schedules initially disrupted by the pandemic have settled back into a pattern that may make it more difficult for a child to get to school. Day care and work schedules may have changed, but not yet readjusted to sync with the school schedule.

In the simplest terms, children and their families may have simply fallen out of the habit of going to school. For children (and maybe their parents) who had always struggled with an unresolved separation anxiety, the time at home — or at least not in school — came as a relief. Which, in turn, meant that any gains in dealing with the anxiety have been undone. The child who was already struggling academically or socially found being at home much less challenging. It’s not surprising that he/she might resist climbing back in the academic saddle.

It is very likely that a significant contributor to the persistent trend in chronic absenteeism is what social scientists call “norm erosion.” Not just children, but families may have developed an attitude that time spent in school just isn’t as valuable as they once believed, or were at least told that it was. There seems to be more parents questioning what their children are being taught in school. The home schooling movement existed before the pandemic. Its roots may be growing under the surface in the form of general skepticism about the importance of school in the bigger scheme of things. The home schooling movement was ready to blossom when the COVID pandemic triggered school closures. We hoped and dreamed that remote learning would be just as good as in-person school. We now realize that, in most cases, that was wishful thinking.

It feels as though a “Perfect Attendance Record” may have lost the cachet it once had. During the pandemic anyone claiming to have never missed a day at school lost that gold star. Did opening your computer every day to watch a remote learning session count for anything?

The threshold for allowing a child to stay home from school may be reaching a historic low. Families seem to regard the school schedule as a guideline that can easily be ignored when planning a vacation. Take little brother out of school to attend big brother’s lacrosse playoff game, not to worry if the youngster misses school days for a trip.

Who is responsible for reversing the trend? Teachers already know it is a serious problem. They view attendance as important. Maybe educators could make school more appealing. But to whom? Sounds like this message should be targeted at the parents. Would stiff penalties for parents whose children are chronically absent help? Would demanding a note from a physician after a certain number of absences help? It might. But, are pediatricians and educators ready to take on one more task in which parents have dropped the ball?

An unknown percentage of chronically absent children are missing school because of a previously unrecognized or inadequately treated mental health condition or learning disability. Involving physicians in a community’s response to chronic absenteeism may be the first step in getting a child back on track. If socioeconomic factors are contributing to a child’s truancy, the involvement of social service agencies may be the answer.

I have a friend who is often asked to address graduating classes at both the high school and college level. One of his standard pieces of advice, whether it be about school or a workplace you may not be in love with, is to at least “show up.” The family that treats school attendance as optional is likely to produce adults who take a similarly nonchalant attitude toward their employment opportunities — with unfortunate results.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Using combined genetic testing in early childhood may decrease the misdiagnosis rate for Global Development Delay (GDD) and may help identify intervention targets, a new study suggests.

Researchers, led by Jiamei Zhang, MS, Department of Rehabilitation Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China, in a multicenter, prospective cohort study enrolled patients ages 12 to 60 months with GDD from six centers in China from July 2020 through August 2023. Participants underwent trio whole exome sequencing (trio-WES) paired with copy number variation sequencing (CNV-seq).

“To the best of our knowledge, this study represents the largest prospective examination of combined genetic testing methods in a GDD cohort,” the authors reported in JAMA Network Open.

GDD is a common neurodevelopmental disorder, marked by cognitive impairment, and affects about 1% of children, the paper states. Most children with GDD develop intellectual disability (ID) after 5 years of age, with implications for quality of life, their physical abilities, and social functioning. Early and accurate diagnosis followed by appropriately targeted treatment is critical, but lacking. Researchers note that there is lack of consensus among health care professionals on whether genetic testing is necessary.

Genetics are known to play a significant role in pathogenesis of GDD, but definitive biomarkers have been elusive.
 

Positive Detection Rate of 61%

In this study, the combined use of trio-WES with CNV-seq in children with early-stage GDD resulted in a positive detection rate of 61%, a significant improvement over performing individual tests, “enhancing the positive detection rate by 18%-40%,” the researchers wrote. The combined approach also saves families time and costs, they note, while leading to more comprehensive genetic analysis and fewer missed diagnoses.

The combined approach also addressed the limitations of trio-WES and CNV-seq used alone, the authors wrote. Because of technological constraints, trio-WES may miss 55% of CNV variations, and CNV-seq has a missed diagnosis rate of 3%.

The study included 434 patients with GDD (60% male; average age, 25 months) with diverse degrees of cognitive impairment: mild (23%); moderate (32%); severe (28%); and profound (17%).

Three characteristics were linked with higher likelihood of having genetic variants: Craniofacial abnormalities (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.45-3.56); moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70); and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35).
 

Dopaminergic Pathway Promising for Treatment

Researchers also discovered that GDD-related genes were primarily enriched in lysosome, dopaminergic synapse, and lysine degradation pathways. Dopaminergic synapse emerged as a significant pathway linked with GDD.

“In this cohort study, our findings support the correlation between dopaminergic synapse and cognitive impairment, as substantiated by prior research and animal models. Therefore, targeting the dopaminergic pathway holds promise for treating GDD and ID,” the authors wrote.

However, the authors note in the limitations that they used only a subset of 100 patients with GDD to measure dopamine concentration.

“Expanding the sample size and conducting in vivo and in vitro experiments are necessary steps to verify whether dopamine can be targeted for clinical precision medical intervention in patients with GDD,” they wrote.

The authors reported no relevant financial relationships.

Using combined genetic testing in early childhood may decrease the misdiagnosis rate for Global Development Delay (GDD) and may help identify intervention targets, a new study suggests.

Researchers, led by Jiamei Zhang, MS, Department of Rehabilitation Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China, in a multicenter, prospective cohort study enrolled patients ages 12 to 60 months with GDD from six centers in China from July 2020 through August 2023. Participants underwent trio whole exome sequencing (trio-WES) paired with copy number variation sequencing (CNV-seq).

“To the best of our knowledge, this study represents the largest prospective examination of combined genetic testing methods in a GDD cohort,” the authors reported in JAMA Network Open.

GDD is a common neurodevelopmental disorder, marked by cognitive impairment, and affects about 1% of children, the paper states. Most children with GDD develop intellectual disability (ID) after 5 years of age, with implications for quality of life, their physical abilities, and social functioning. Early and accurate diagnosis followed by appropriately targeted treatment is critical, but lacking. Researchers note that there is lack of consensus among health care professionals on whether genetic testing is necessary.

Genetics are known to play a significant role in pathogenesis of GDD, but definitive biomarkers have been elusive.
 

Positive Detection Rate of 61%

In this study, the combined use of trio-WES with CNV-seq in children with early-stage GDD resulted in a positive detection rate of 61%, a significant improvement over performing individual tests, “enhancing the positive detection rate by 18%-40%,” the researchers wrote. The combined approach also saves families time and costs, they note, while leading to more comprehensive genetic analysis and fewer missed diagnoses.

The combined approach also addressed the limitations of trio-WES and CNV-seq used alone, the authors wrote. Because of technological constraints, trio-WES may miss 55% of CNV variations, and CNV-seq has a missed diagnosis rate of 3%.

The study included 434 patients with GDD (60% male; average age, 25 months) with diverse degrees of cognitive impairment: mild (23%); moderate (32%); severe (28%); and profound (17%).

Three characteristics were linked with higher likelihood of having genetic variants: Craniofacial abnormalities (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.45-3.56); moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70); and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35).
 

Dopaminergic Pathway Promising for Treatment

Researchers also discovered that GDD-related genes were primarily enriched in lysosome, dopaminergic synapse, and lysine degradation pathways. Dopaminergic synapse emerged as a significant pathway linked with GDD.

“In this cohort study, our findings support the correlation between dopaminergic synapse and cognitive impairment, as substantiated by prior research and animal models. Therefore, targeting the dopaminergic pathway holds promise for treating GDD and ID,” the authors wrote.

However, the authors note in the limitations that they used only a subset of 100 patients with GDD to measure dopamine concentration.

“Expanding the sample size and conducting in vivo and in vitro experiments are necessary steps to verify whether dopamine can be targeted for clinical precision medical intervention in patients with GDD,” they wrote.

The authors reported no relevant financial relationships.

Using combined genetic testing in early childhood may decrease the misdiagnosis rate for Global Development Delay (GDD) and may help identify intervention targets, a new study suggests.

Researchers, led by Jiamei Zhang, MS, Department of Rehabilitation Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China, in a multicenter, prospective cohort study enrolled patients ages 12 to 60 months with GDD from six centers in China from July 2020 through August 2023. Participants underwent trio whole exome sequencing (trio-WES) paired with copy number variation sequencing (CNV-seq).

“To the best of our knowledge, this study represents the largest prospective examination of combined genetic testing methods in a GDD cohort,” the authors reported in JAMA Network Open.

GDD is a common neurodevelopmental disorder, marked by cognitive impairment, and affects about 1% of children, the paper states. Most children with GDD develop intellectual disability (ID) after 5 years of age, with implications for quality of life, their physical abilities, and social functioning. Early and accurate diagnosis followed by appropriately targeted treatment is critical, but lacking. Researchers note that there is lack of consensus among health care professionals on whether genetic testing is necessary.

Genetics are known to play a significant role in pathogenesis of GDD, but definitive biomarkers have been elusive.
 

Positive Detection Rate of 61%

In this study, the combined use of trio-WES with CNV-seq in children with early-stage GDD resulted in a positive detection rate of 61%, a significant improvement over performing individual tests, “enhancing the positive detection rate by 18%-40%,” the researchers wrote. The combined approach also saves families time and costs, they note, while leading to more comprehensive genetic analysis and fewer missed diagnoses.

The combined approach also addressed the limitations of trio-WES and CNV-seq used alone, the authors wrote. Because of technological constraints, trio-WES may miss 55% of CNV variations, and CNV-seq has a missed diagnosis rate of 3%.

The study included 434 patients with GDD (60% male; average age, 25 months) with diverse degrees of cognitive impairment: mild (23%); moderate (32%); severe (28%); and profound (17%).

Three characteristics were linked with higher likelihood of having genetic variants: Craniofacial abnormalities (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.45-3.56); moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70); and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35).
 

Dopaminergic Pathway Promising for Treatment

Researchers also discovered that GDD-related genes were primarily enriched in lysosome, dopaminergic synapse, and lysine degradation pathways. Dopaminergic synapse emerged as a significant pathway linked with GDD.

“In this cohort study, our findings support the correlation between dopaminergic synapse and cognitive impairment, as substantiated by prior research and animal models. Therefore, targeting the dopaminergic pathway holds promise for treating GDD and ID,” the authors wrote.

However, the authors note in the limitations that they used only a subset of 100 patients with GDD to measure dopamine concentration.

“Expanding the sample size and conducting in vivo and in vitro experiments are necessary steps to verify whether dopamine can be targeted for clinical precision medical intervention in patients with GDD,” they wrote.

The authors reported no relevant financial relationships.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. 
 

The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician’s office. Important highlights from these recommended strategies to reduce ACEs include:

• Strengthen economic support for families through policies such as the earned income tax credit and child tax credit.
• Establish routine parental work/shift times to optimize cognitive outcomes in children.
• Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence.
• Facilitate early in-home visitation for at-risk families as well as high-quality childcare.
• Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success.
• Connect youth to after-school programs featuring caring adults.

But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient’s past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation.

The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are “parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity.” Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to “[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change.” 

These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by “high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments.” This micro and macro lens fosters a deeper clinician understanding of a patient’s trauma origin and can better guide appropriate clinical follow-up. 

ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term health care complications, costly for both patient and the health care system. 

After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community, to offer clinical interventions and services to mitigate patients’ toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. 

The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow:

• Utilize technology to implement a streamlined referral processing/tracking system.
• Train clinicians to respond competently to positive ACE screens.
• Gather in-network and community-based resources for patients.

In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in after-school programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. 

Dr. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, disclosed ties with McNeil Pharmaceuticals. Alejandra Hurtado, MD candidate, University of California, Irvine School of Medicine, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Almost all primary care providers (PCPs) have taken on diagnosing and managing ADHD. With about 12% of school aged children affected, typical PCPs can expect about 240 children with ADHD under their care. Adopting this primary care function has been helped by having clear diagnostic criteria for the three DMS 5 “presentations” of ADHD, open source tools (e.g. Vanderbilts), expectation of collaboration by educators, American Academy of Pediatrics (AAP) guidelines for diagnosis and management, Society for Developmental–Behavioral Pediatrics guidelines for “complex ADHD,” and access to effective medication treatments PCPs can provide (although less so for behavioral ones), cultural acceptance of individuals with ADHD, and especially reliable payment by insurers.

Screening

But what about PCP management of autism spectrum disorder (ASD), now affecting 2.8%, for an expected 60 children under care for each of us? PCP detection and care for children with ASD is more complex than ADHD, but even more essential, so we need to learn the skills. It is more essential because very early detection and entry into evidence-based intervention has long-term benefits for the child and family that are not as crucial for ADHD. While ADHD symptoms may not impact functioning until age 7 or even 12 years of age, signs of ASD usually emerge earlier (by 18 months) but gradually and about 30% after apparently normal development even to age 2 years.

Screening is crucial, but unfortunately not perfect. Recent AAP surveys show that most PCPs screen for autism at the recommended 18 and 24 months. But what happens after that? How many offices are tracking referrals for positive screens for needed evaluations and early intervention? Our data shows that tracking is rarely done and children do not start to get the benefit of early intervention until 4.5 years of age, on average.
 

Diagnostic Testing

And screening is the easiest part of addressing ASD. Wait times for diagnostic testing can be agonizing months to years. Multiple programs are training PCPs to perform hands-on 10- to 30-minute secondary screening with considerable success. You can become proficient on tools such as STAT (Screening Tool for Autism in Two-Year-Olds), RITA-T (Rapid Interactive Screening Test for Autism in Toddlers), BISCUIT (Baby and Infant Screen for Children with Autism Traits), SORF (Systematic Observation of Red Flags), ADEC (Autism Detection in Early Childhood) or CARS (Childhood Autism Rating Scale) with a few hours of training. Even secondary assessments done virtually by PCPs such as TELE-ASD-PEDS quite accurately predict a verifiable ASD diagnosis for those referred by concerns. Some problems of the reported accuracy of these secondary screening processes have to do with validation in samples of children for whom parents or clinicians already had concern and generally not including many younger children in whom it is so important to detect. Level of confidence of developmental and behavioral pediatricians of the presence of ASD is highly related to ultimate diagnosis. But success with PCPs’ mastering secondary screening has not yet been reported to convince insurers to approve payment for intervention services such as Applied Behavior Analysis (ABA).

Comorbidity

Co-existing conditions affect the majority of patients with ASD (70%), compared with ADHD, but with a broader range and more debilitating and difficult to manage conditions. More medical co-existing issues such as intellectual disability (25%-75%), seizures (12%-26%), motor incoordination (51%), GI conditions (9%-91%), sleep difficulty (50%-80%), sleep apnea, congenital heart disease, avoidant-restrictive food intake disorder, autoimmune disorders, and genetic syndromes (e.g. Fragile X, tuberous sclerosis, Down, Angelman’s, untreated PKU, neurofibromatosis, Klinefelter syndrome) reflect the range of underpinnings of ASD. The need to detect and manage these co-existing issues, besides assessing hearing and vision, makes our skilled involvement and vigilance in ASD care essential. Referring for help from OTs, PTs, speech pathologists, neurologists, psychologists, and special educators as issues in their domains are prioritized is also our responsibility. We must also help families balance utilizing these resources so as to avoid overwhelm.

Anxiety (50%), ADHD (37%-85%), depression (54%), bipolar (7.3%), suicidal ideation (40% starting < 8 years), and emotion dysregulation, familiar to us from our management of ADHD, may develop but are often less well defined and more intractable in ASD, making use of screening tools essential. Using a system like CHADIS that has online pre-visit and monitoring screens delivered based on algorithms for the numerous co-existing conditions, automated handouts, and functions to make and track referral success can facilitate care for this complex chronic condition. Identifying mental health providers with ASD expertise is more difficult, so more management is on us. While medications for these conditions can be beneficial, we need to learn to use lower doses, slower dose increases, and employ problem-solving of side effects with more parent collaboration than for ADHD as children with ASD often cannot self-report effectively. We need to ask about the common ad hoc use of complementary medications and substances (32%-87%) that may be complicating. Of course, these conditions and the caveats of management require more of our time with the patient and family as well as communication with the many other professionals involved. It is important to set our own and our families’ expectations (and schedules) for much more frequent contact and also to bill appropriately with chronic care (99487,89,90) and collaborative care CPT codes (99492,3,4 or G2214).
 

Behavioral Manifestations

During our care, the often extreme behavioral manifestations of ASD may be the most pressing issues. We need new understanding and skills to sort out and counsel on inflexible, explosive, and sensory triggered behaviors. Just as for ADHD, using the approach of Functional Behavioral Assessment and plans for home as well as school behavior can be key. More difficult in ASD is looking for physical causes, since the child may not provide clear cues because of communication and sensory differences. Conditions common in children with ASD such as constipation, dental caries, otitis, dietary intolerances, allergies, migraine, sleep deficits, menstrual cramps, or fears and changes from puberty manifesting behaviorally are often tricky to sort out.

While the diagnosis of ASD, as for ADHD, does not require any laboratory testing, looking for possible causes is important information for the family and someday may also lead to genetic or other therapies. We need to know that recommendations include screening for Ferritin, Pb, chromosomal microarray and FMR I testing as well as checking that PKU was normal; MECP 2 is indicated in females and symptomatic males; and PTENS testing for children with head circumference greater than 2.5-3 SD. Metabolic and mitochondrial assays are indicated only when symptoms suggest. We need to develop confidence to reserve MRIs or EEGs for cases with abnormal neuro. exams, regression, or history of seizures. It is demanding to keep up with AAP recommendations in this very active area of research.
 

Interventions

The interventions for ADHD are generally school accommodations and therapies for comorbidities. In contrast, since core social communication skills are the main deficit in ASD, all children screened positive for ASD should be referred for early intervention while awaiting, as well as after, diagnosis. While all states have no or low-cost early intervention, quality and quantity (of hours offered) varies. We should also recommend and try to determine if evidence-based intervention is being provided, such as pivotal response training, UCLA discrete trial therapy, Carbone’s verbal behavior, applied behavior analysis (ABA), Early Start Denver Model, and sometimes music and social skills trainings (effect size 0.42-0.76). Such professional interventions have best evidence with more than 25 hours/week but 15 hours has benefit for higher functioning children. CBT can help anxiety even in younger children. One way for families to provide more hours and more generalizable intervention is coaching by the PLAY Project or DIRFloortime, parent mediated interventions with evidence, some with training both in person or online. Alternative communication training and other condition specific assistance are often needed (e.g. Picture Exchange Communication System for nonverbal children).

While we should already be familiar with writing 504 plan and IEP requests to schools, which also apply to children with ASD, in addition we need to be ready to advise about other legal rights including autism waivers, wraparound services, guardianship, and trust accounts. We can share quality educational materials available online (e.g. from Autism Speaks, SPARK, and Autism Navigator). Social media groups may be supportive, but also may contain disinformation we need to dispel.

Unfortunately, templates, questionnaires, and lack of interdisciplinary referral and communication functions of EHRs don’t support the complexities of care for ASD. While the AAP has guidelines for diagnosis and management and an online toolkit, consider adding a system with an autism-specific module like CHADIS and joining the Autism Care Network or ECHO Autism sessions to get both information and support to take on the evolving critical role of autism care.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Almost all primary care providers (PCPs) have taken on diagnosing and managing ADHD. With about 12% of school aged children affected, typical PCPs can expect about 240 children with ADHD under their care. Adopting this primary care function has been helped by having clear diagnostic criteria for the three DMS 5 “presentations” of ADHD, open source tools (e.g. Vanderbilts), expectation of collaboration by educators, American Academy of Pediatrics (AAP) guidelines for diagnosis and management, Society for Developmental–Behavioral Pediatrics guidelines for “complex ADHD,” and access to effective medication treatments PCPs can provide (although less so for behavioral ones), cultural acceptance of individuals with ADHD, and especially reliable payment by insurers.

Screening

But what about PCP management of autism spectrum disorder (ASD), now affecting 2.8%, for an expected 60 children under care for each of us? PCP detection and care for children with ASD is more complex than ADHD, but even more essential, so we need to learn the skills. It is more essential because very early detection and entry into evidence-based intervention has long-term benefits for the child and family that are not as crucial for ADHD. While ADHD symptoms may not impact functioning until age 7 or even 12 years of age, signs of ASD usually emerge earlier (by 18 months) but gradually and about 30% after apparently normal development even to age 2 years.

Screening is crucial, but unfortunately not perfect. Recent AAP surveys show that most PCPs screen for autism at the recommended 18 and 24 months. But what happens after that? How many offices are tracking referrals for positive screens for needed evaluations and early intervention? Our data shows that tracking is rarely done and children do not start to get the benefit of early intervention until 4.5 years of age, on average.
 

Diagnostic Testing

And screening is the easiest part of addressing ASD. Wait times for diagnostic testing can be agonizing months to years. Multiple programs are training PCPs to perform hands-on 10- to 30-minute secondary screening with considerable success. You can become proficient on tools such as STAT (Screening Tool for Autism in Two-Year-Olds), RITA-T (Rapid Interactive Screening Test for Autism in Toddlers), BISCUIT (Baby and Infant Screen for Children with Autism Traits), SORF (Systematic Observation of Red Flags), ADEC (Autism Detection in Early Childhood) or CARS (Childhood Autism Rating Scale) with a few hours of training. Even secondary assessments done virtually by PCPs such as TELE-ASD-PEDS quite accurately predict a verifiable ASD diagnosis for those referred by concerns. Some problems of the reported accuracy of these secondary screening processes have to do with validation in samples of children for whom parents or clinicians already had concern and generally not including many younger children in whom it is so important to detect. Level of confidence of developmental and behavioral pediatricians of the presence of ASD is highly related to ultimate diagnosis. But success with PCPs’ mastering secondary screening has not yet been reported to convince insurers to approve payment for intervention services such as Applied Behavior Analysis (ABA).

Comorbidity

Co-existing conditions affect the majority of patients with ASD (70%), compared with ADHD, but with a broader range and more debilitating and difficult to manage conditions. More medical co-existing issues such as intellectual disability (25%-75%), seizures (12%-26%), motor incoordination (51%), GI conditions (9%-91%), sleep difficulty (50%-80%), sleep apnea, congenital heart disease, avoidant-restrictive food intake disorder, autoimmune disorders, and genetic syndromes (e.g. Fragile X, tuberous sclerosis, Down, Angelman’s, untreated PKU, neurofibromatosis, Klinefelter syndrome) reflect the range of underpinnings of ASD. The need to detect and manage these co-existing issues, besides assessing hearing and vision, makes our skilled involvement and vigilance in ASD care essential. Referring for help from OTs, PTs, speech pathologists, neurologists, psychologists, and special educators as issues in their domains are prioritized is also our responsibility. We must also help families balance utilizing these resources so as to avoid overwhelm.

Anxiety (50%), ADHD (37%-85%), depression (54%), bipolar (7.3%), suicidal ideation (40% starting < 8 years), and emotion dysregulation, familiar to us from our management of ADHD, may develop but are often less well defined and more intractable in ASD, making use of screening tools essential. Using a system like CHADIS that has online pre-visit and monitoring screens delivered based on algorithms for the numerous co-existing conditions, automated handouts, and functions to make and track referral success can facilitate care for this complex chronic condition. Identifying mental health providers with ASD expertise is more difficult, so more management is on us. While medications for these conditions can be beneficial, we need to learn to use lower doses, slower dose increases, and employ problem-solving of side effects with more parent collaboration than for ADHD as children with ASD often cannot self-report effectively. We need to ask about the common ad hoc use of complementary medications and substances (32%-87%) that may be complicating. Of course, these conditions and the caveats of management require more of our time with the patient and family as well as communication with the many other professionals involved. It is important to set our own and our families’ expectations (and schedules) for much more frequent contact and also to bill appropriately with chronic care (99487,89,90) and collaborative care CPT codes (99492,3,4 or G2214).
 

Behavioral Manifestations

During our care, the often extreme behavioral manifestations of ASD may be the most pressing issues. We need new understanding and skills to sort out and counsel on inflexible, explosive, and sensory triggered behaviors. Just as for ADHD, using the approach of Functional Behavioral Assessment and plans for home as well as school behavior can be key. More difficult in ASD is looking for physical causes, since the child may not provide clear cues because of communication and sensory differences. Conditions common in children with ASD such as constipation, dental caries, otitis, dietary intolerances, allergies, migraine, sleep deficits, menstrual cramps, or fears and changes from puberty manifesting behaviorally are often tricky to sort out.

While the diagnosis of ASD, as for ADHD, does not require any laboratory testing, looking for possible causes is important information for the family and someday may also lead to genetic or other therapies. We need to know that recommendations include screening for Ferritin, Pb, chromosomal microarray and FMR I testing as well as checking that PKU was normal; MECP 2 is indicated in females and symptomatic males; and PTENS testing for children with head circumference greater than 2.5-3 SD. Metabolic and mitochondrial assays are indicated only when symptoms suggest. We need to develop confidence to reserve MRIs or EEGs for cases with abnormal neuro. exams, regression, or history of seizures. It is demanding to keep up with AAP recommendations in this very active area of research.
 

Interventions

The interventions for ADHD are generally school accommodations and therapies for comorbidities. In contrast, since core social communication skills are the main deficit in ASD, all children screened positive for ASD should be referred for early intervention while awaiting, as well as after, diagnosis. While all states have no or low-cost early intervention, quality and quantity (of hours offered) varies. We should also recommend and try to determine if evidence-based intervention is being provided, such as pivotal response training, UCLA discrete trial therapy, Carbone’s verbal behavior, applied behavior analysis (ABA), Early Start Denver Model, and sometimes music and social skills trainings (effect size 0.42-0.76). Such professional interventions have best evidence with more than 25 hours/week but 15 hours has benefit for higher functioning children. CBT can help anxiety even in younger children. One way for families to provide more hours and more generalizable intervention is coaching by the PLAY Project or DIRFloortime, parent mediated interventions with evidence, some with training both in person or online. Alternative communication training and other condition specific assistance are often needed (e.g. Picture Exchange Communication System for nonverbal children).

While we should already be familiar with writing 504 plan and IEP requests to schools, which also apply to children with ASD, in addition we need to be ready to advise about other legal rights including autism waivers, wraparound services, guardianship, and trust accounts. We can share quality educational materials available online (e.g. from Autism Speaks, SPARK, and Autism Navigator). Social media groups may be supportive, but also may contain disinformation we need to dispel.

Unfortunately, templates, questionnaires, and lack of interdisciplinary referral and communication functions of EHRs don’t support the complexities of care for ASD. While the AAP has guidelines for diagnosis and management and an online toolkit, consider adding a system with an autism-specific module like CHADIS and joining the Autism Care Network or ECHO Autism sessions to get both information and support to take on the evolving critical role of autism care.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Almost all primary care providers (PCPs) have taken on diagnosing and managing ADHD. With about 12% of school aged children affected, typical PCPs can expect about 240 children with ADHD under their care. Adopting this primary care function has been helped by having clear diagnostic criteria for the three DMS 5 “presentations” of ADHD, open source tools (e.g. Vanderbilts), expectation of collaboration by educators, American Academy of Pediatrics (AAP) guidelines for diagnosis and management, Society for Developmental–Behavioral Pediatrics guidelines for “complex ADHD,” and access to effective medication treatments PCPs can provide (although less so for behavioral ones), cultural acceptance of individuals with ADHD, and especially reliable payment by insurers.

Screening

But what about PCP management of autism spectrum disorder (ASD), now affecting 2.8%, for an expected 60 children under care for each of us? PCP detection and care for children with ASD is more complex than ADHD, but even more essential, so we need to learn the skills. It is more essential because very early detection and entry into evidence-based intervention has long-term benefits for the child and family that are not as crucial for ADHD. While ADHD symptoms may not impact functioning until age 7 or even 12 years of age, signs of ASD usually emerge earlier (by 18 months) but gradually and about 30% after apparently normal development even to age 2 years.

Screening is crucial, but unfortunately not perfect. Recent AAP surveys show that most PCPs screen for autism at the recommended 18 and 24 months. But what happens after that? How many offices are tracking referrals for positive screens for needed evaluations and early intervention? Our data shows that tracking is rarely done and children do not start to get the benefit of early intervention until 4.5 years of age, on average.
 

Diagnostic Testing

And screening is the easiest part of addressing ASD. Wait times for diagnostic testing can be agonizing months to years. Multiple programs are training PCPs to perform hands-on 10- to 30-minute secondary screening with considerable success. You can become proficient on tools such as STAT (Screening Tool for Autism in Two-Year-Olds), RITA-T (Rapid Interactive Screening Test for Autism in Toddlers), BISCUIT (Baby and Infant Screen for Children with Autism Traits), SORF (Systematic Observation of Red Flags), ADEC (Autism Detection in Early Childhood) or CARS (Childhood Autism Rating Scale) with a few hours of training. Even secondary assessments done virtually by PCPs such as TELE-ASD-PEDS quite accurately predict a verifiable ASD diagnosis for those referred by concerns. Some problems of the reported accuracy of these secondary screening processes have to do with validation in samples of children for whom parents or clinicians already had concern and generally not including many younger children in whom it is so important to detect. Level of confidence of developmental and behavioral pediatricians of the presence of ASD is highly related to ultimate diagnosis. But success with PCPs’ mastering secondary screening has not yet been reported to convince insurers to approve payment for intervention services such as Applied Behavior Analysis (ABA).

Comorbidity

Co-existing conditions affect the majority of patients with ASD (70%), compared with ADHD, but with a broader range and more debilitating and difficult to manage conditions. More medical co-existing issues such as intellectual disability (25%-75%), seizures (12%-26%), motor incoordination (51%), GI conditions (9%-91%), sleep difficulty (50%-80%), sleep apnea, congenital heart disease, avoidant-restrictive food intake disorder, autoimmune disorders, and genetic syndromes (e.g. Fragile X, tuberous sclerosis, Down, Angelman’s, untreated PKU, neurofibromatosis, Klinefelter syndrome) reflect the range of underpinnings of ASD. The need to detect and manage these co-existing issues, besides assessing hearing and vision, makes our skilled involvement and vigilance in ASD care essential. Referring for help from OTs, PTs, speech pathologists, neurologists, psychologists, and special educators as issues in their domains are prioritized is also our responsibility. We must also help families balance utilizing these resources so as to avoid overwhelm.

Anxiety (50%), ADHD (37%-85%), depression (54%), bipolar (7.3%), suicidal ideation (40% starting < 8 years), and emotion dysregulation, familiar to us from our management of ADHD, may develop but are often less well defined and more intractable in ASD, making use of screening tools essential. Using a system like CHADIS that has online pre-visit and monitoring screens delivered based on algorithms for the numerous co-existing conditions, automated handouts, and functions to make and track referral success can facilitate care for this complex chronic condition. Identifying mental health providers with ASD expertise is more difficult, so more management is on us. While medications for these conditions can be beneficial, we need to learn to use lower doses, slower dose increases, and employ problem-solving of side effects with more parent collaboration than for ADHD as children with ASD often cannot self-report effectively. We need to ask about the common ad hoc use of complementary medications and substances (32%-87%) that may be complicating. Of course, these conditions and the caveats of management require more of our time with the patient and family as well as communication with the many other professionals involved. It is important to set our own and our families’ expectations (and schedules) for much more frequent contact and also to bill appropriately with chronic care (99487,89,90) and collaborative care CPT codes (99492,3,4 or G2214).
 

Behavioral Manifestations

During our care, the often extreme behavioral manifestations of ASD may be the most pressing issues. We need new understanding and skills to sort out and counsel on inflexible, explosive, and sensory triggered behaviors. Just as for ADHD, using the approach of Functional Behavioral Assessment and plans for home as well as school behavior can be key. More difficult in ASD is looking for physical causes, since the child may not provide clear cues because of communication and sensory differences. Conditions common in children with ASD such as constipation, dental caries, otitis, dietary intolerances, allergies, migraine, sleep deficits, menstrual cramps, or fears and changes from puberty manifesting behaviorally are often tricky to sort out.

While the diagnosis of ASD, as for ADHD, does not require any laboratory testing, looking for possible causes is important information for the family and someday may also lead to genetic or other therapies. We need to know that recommendations include screening for Ferritin, Pb, chromosomal microarray and FMR I testing as well as checking that PKU was normal; MECP 2 is indicated in females and symptomatic males; and PTENS testing for children with head circumference greater than 2.5-3 SD. Metabolic and mitochondrial assays are indicated only when symptoms suggest. We need to develop confidence to reserve MRIs or EEGs for cases with abnormal neuro. exams, regression, or history of seizures. It is demanding to keep up with AAP recommendations in this very active area of research.
 

Interventions

The interventions for ADHD are generally school accommodations and therapies for comorbidities. In contrast, since core social communication skills are the main deficit in ASD, all children screened positive for ASD should be referred for early intervention while awaiting, as well as after, diagnosis. While all states have no or low-cost early intervention, quality and quantity (of hours offered) varies. We should also recommend and try to determine if evidence-based intervention is being provided, such as pivotal response training, UCLA discrete trial therapy, Carbone’s verbal behavior, applied behavior analysis (ABA), Early Start Denver Model, and sometimes music and social skills trainings (effect size 0.42-0.76). Such professional interventions have best evidence with more than 25 hours/week but 15 hours has benefit for higher functioning children. CBT can help anxiety even in younger children. One way for families to provide more hours and more generalizable intervention is coaching by the PLAY Project or DIRFloortime, parent mediated interventions with evidence, some with training both in person or online. Alternative communication training and other condition specific assistance are often needed (e.g. Picture Exchange Communication System for nonverbal children).

While we should already be familiar with writing 504 plan and IEP requests to schools, which also apply to children with ASD, in addition we need to be ready to advise about other legal rights including autism waivers, wraparound services, guardianship, and trust accounts. We can share quality educational materials available online (e.g. from Autism Speaks, SPARK, and Autism Navigator). Social media groups may be supportive, but also may contain disinformation we need to dispel.

Unfortunately, templates, questionnaires, and lack of interdisciplinary referral and communication functions of EHRs don’t support the complexities of care for ASD. While the AAP has guidelines for diagnosis and management and an online toolkit, consider adding a system with an autism-specific module like CHADIS and joining the Autism Care Network or ECHO Autism sessions to get both information and support to take on the evolving critical role of autism care.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about anxiety?

Paul N. Williams, MD: Always. It’s one of my favorite topics. 

Dr. Watto: We had a great guest for this podcast on anxiety — Dr. Jessi Gold, who gave us a lot of practical tips. The way she talks to her patients about anxiety is really useful. When patients say “my anxiety” or “I feel anxious,” she considers that a symptom. Anxiety can be a diagnosis or a symptom. You need to clarify what they mean when they refer to their anxiety and dig into how it affects their life. 

We asked her about the Generalized Anxiety Disorder (GAD)-7 score. Like most of the experts we’ve talked to, she’s internalized that, so she doesn’t need to rely on a questionnaire. But I still rely on a questionnaire when I’m taking a history for anxiety. 

We also asked her how she explains anxiety to patients. I don’t know about you, Paul, but I’ve never really thought about explaining to patients why they have anxiety. 

Dr. Williams: I’ve done my best to try to normalize it, but I haven’t actually talked to patients about the evolutionary advantage of anxiety. 

Dr. Watto: She frames it to patients this way: As we were evolving, it was somewhat of an advantage to be hypervigilant, to have some anxiety and a healthy amount of fear so that you weren’t killed or eaten. But now, in the modern world, anxiety isn’t playing to our advantage. Anxiety is not making them safer; it’s making their lives worse. She explains to patients that she’s trying to help them overcome that. 

In terms of pharmacotherapy for anxiety, I always think about SSRIs as one of the first steps. Why not use an SNRI as first-line treatment?

Dr. Williams: I was glad we had this conversation because I feel, for whatever reason, a bit more comfortable treating depression than anxiety. In any case, Dr. Gold reaches for the SSRI first, in part because getting off an SNRI (for example, to switch to something else) can be absolutely miserable. The discontinuation effects can be severe enough to have to bridge some patients with a benzodiazepine to get them fully off the SNRI. So, an SNRI is not the first drug you should necessarily reach for. 

She thinks about using an SNRI if she has tried a couple of SSRIs that have been ineffective, or if the patient has a comorbid condition that might also benefit from the SNRI in the same way that you might use a tricyclic antidepressant in the patient with both migraines and anxiety. An SNRI might be a good medication to consider in the patient with neuropathic pain and anxiety but rarely as a first-line treatment, because if it doesn’t work out, getting the patient off that medication can be a challenge.

Dr. Watto: She mentioned venlafaxine as being especially difficult to get people off of. I’ve heard that bupropion should never be used in anxiety, and if you give it, you are a terrible doctor. What did we learn about that? 

Dr. Williams: It’s a drug I’ve hesitated to prescribe to patients with anxiety or even comorbid anxiety. I’m a little bit nervous for someone who has depression and anxiety to prescribe bupropion because it can be activating and make things worse. But Dr. Gold says that she has seen bupropion work for some patients so she will consider it, especially for patients who don’t want to gain weight, or for whom sexual side effects would be bothersome. So, it’s not always the wrong answer. In her expert opinion, you can try it and see how the patient responds, using shared decision-making and letting the patient know that they may not tolerate it as well as other medications. 

Dr. Watto: She sees a lot of younger people — students, working professionals — who do not want to gain weight, and that’s understandable. She will tell patients, “We can try bupropion, but if you get more anxious, we might not be able to continue it. We might have to use one of the first-line agents instead.” 

Dr. Williams: We talked about mirtazapine as well. She tells patients they are going to gain weight with it. You have to have that conversation with the patient to see whether that is something they are willing to tolerate. If so, mirtazapine might be worth a try, but you have to be upfront about the potential side effects and know what the medications you’re prescribing will do to patients. 

Dr. Watto: We asked her about benzodiazepines. For as-needed medication for people who are experiencing panic or anxiety attacks, she prescribes propranolol 10-20 mg twice a day as needed, which is a low dose. In primary care, we use higher doses for migraine prophylaxis. 

She uses propranolol because for some patients, it’s the physical symptoms of anxiety that are bothering them. She can calm down the physical symptoms with that and get by without needing to use a benzodiazepine. 

But what about thoughts that make people anxious? Can we change people’s thoughts with medication? 

Dr. Williams: Dr. Gold made the point that we can medicate away insomnia, for the most part. We can medicate away the physical symptoms of anxiety, which can be really bothersome. But we can’t medicate away thoughts and thought patterns. You can make patients feel better with medications, but you may not be able to get rid of the persistent bothersome thoughts. That’s where cognitive-behavioral therapy can be especially helpful. Most of these patients would benefit from therapy.

Dr. Watto: I completely agree with that. We talked about so many great things with Dr. Gold, but we can’t recap all of it here. Please click on this link to hear the full podcast episode. 
 

Dr. Watto is Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Lewis Katz School of Medicine; Staff Physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He disclosed receiving income from The Curbsiders. The Curbsiders is an internal medicine podcast, in which three board-certified internists interview experts on clinically important topics. In a collaboration with Medscape, the Curbsiders share clinical pearls and practice-changing knowledge from selected podcasts.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about anxiety?

Paul N. Williams, MD: Always. It’s one of my favorite topics. 

Dr. Watto: We had a great guest for this podcast on anxiety — Dr. Jessi Gold, who gave us a lot of practical tips. The way she talks to her patients about anxiety is really useful. When patients say “my anxiety” or “I feel anxious,” she considers that a symptom. Anxiety can be a diagnosis or a symptom. You need to clarify what they mean when they refer to their anxiety and dig into how it affects their life. 

We asked her about the Generalized Anxiety Disorder (GAD)-7 score. Like most of the experts we’ve talked to, she’s internalized that, so she doesn’t need to rely on a questionnaire. But I still rely on a questionnaire when I’m taking a history for anxiety. 

We also asked her how she explains anxiety to patients. I don’t know about you, Paul, but I’ve never really thought about explaining to patients why they have anxiety. 

Dr. Williams: I’ve done my best to try to normalize it, but I haven’t actually talked to patients about the evolutionary advantage of anxiety. 

Dr. Watto: She frames it to patients this way: As we were evolving, it was somewhat of an advantage to be hypervigilant, to have some anxiety and a healthy amount of fear so that you weren’t killed or eaten. But now, in the modern world, anxiety isn’t playing to our advantage. Anxiety is not making them safer; it’s making their lives worse. She explains to patients that she’s trying to help them overcome that. 

In terms of pharmacotherapy for anxiety, I always think about SSRIs as one of the first steps. Why not use an SNRI as first-line treatment?

Dr. Williams: I was glad we had this conversation because I feel, for whatever reason, a bit more comfortable treating depression than anxiety. In any case, Dr. Gold reaches for the SSRI first, in part because getting off an SNRI (for example, to switch to something else) can be absolutely miserable. The discontinuation effects can be severe enough to have to bridge some patients with a benzodiazepine to get them fully off the SNRI. So, an SNRI is not the first drug you should necessarily reach for. 

She thinks about using an SNRI if she has tried a couple of SSRIs that have been ineffective, or if the patient has a comorbid condition that might also benefit from the SNRI in the same way that you might use a tricyclic antidepressant in the patient with both migraines and anxiety. An SNRI might be a good medication to consider in the patient with neuropathic pain and anxiety but rarely as a first-line treatment, because if it doesn’t work out, getting the patient off that medication can be a challenge.

Dr. Watto: She mentioned venlafaxine as being especially difficult to get people off of. I’ve heard that bupropion should never be used in anxiety, and if you give it, you are a terrible doctor. What did we learn about that? 

Dr. Williams: It’s a drug I’ve hesitated to prescribe to patients with anxiety or even comorbid anxiety. I’m a little bit nervous for someone who has depression and anxiety to prescribe bupropion because it can be activating and make things worse. But Dr. Gold says that she has seen bupropion work for some patients so she will consider it, especially for patients who don’t want to gain weight, or for whom sexual side effects would be bothersome. So, it’s not always the wrong answer. In her expert opinion, you can try it and see how the patient responds, using shared decision-making and letting the patient know that they may not tolerate it as well as other medications. 

Dr. Watto: She sees a lot of younger people — students, working professionals — who do not want to gain weight, and that’s understandable. She will tell patients, “We can try bupropion, but if you get more anxious, we might not be able to continue it. We might have to use one of the first-line agents instead.” 

Dr. Williams: We talked about mirtazapine as well. She tells patients they are going to gain weight with it. You have to have that conversation with the patient to see whether that is something they are willing to tolerate. If so, mirtazapine might be worth a try, but you have to be upfront about the potential side effects and know what the medications you’re prescribing will do to patients. 

Dr. Watto: We asked her about benzodiazepines. For as-needed medication for people who are experiencing panic or anxiety attacks, she prescribes propranolol 10-20 mg twice a day as needed, which is a low dose. In primary care, we use higher doses for migraine prophylaxis. 

She uses propranolol because for some patients, it’s the physical symptoms of anxiety that are bothering them. She can calm down the physical symptoms with that and get by without needing to use a benzodiazepine. 

But what about thoughts that make people anxious? Can we change people’s thoughts with medication? 

Dr. Williams: Dr. Gold made the point that we can medicate away insomnia, for the most part. We can medicate away the physical symptoms of anxiety, which can be really bothersome. But we can’t medicate away thoughts and thought patterns. You can make patients feel better with medications, but you may not be able to get rid of the persistent bothersome thoughts. That’s where cognitive-behavioral therapy can be especially helpful. Most of these patients would benefit from therapy.

Dr. Watto: I completely agree with that. We talked about so many great things with Dr. Gold, but we can’t recap all of it here. Please click on this link to hear the full podcast episode. 
 

Dr. Watto is Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Lewis Katz School of Medicine; Staff Physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He disclosed receiving income from The Curbsiders. The Curbsiders is an internal medicine podcast, in which three board-certified internists interview experts on clinically important topics. In a collaboration with Medscape, the Curbsiders share clinical pearls and practice-changing knowledge from selected podcasts.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about anxiety?

Paul N. Williams, MD: Always. It’s one of my favorite topics. 

Dr. Watto: We had a great guest for this podcast on anxiety — Dr. Jessi Gold, who gave us a lot of practical tips. The way she talks to her patients about anxiety is really useful. When patients say “my anxiety” or “I feel anxious,” she considers that a symptom. Anxiety can be a diagnosis or a symptom. You need to clarify what they mean when they refer to their anxiety and dig into how it affects their life. 

We asked her about the Generalized Anxiety Disorder (GAD)-7 score. Like most of the experts we’ve talked to, she’s internalized that, so she doesn’t need to rely on a questionnaire. But I still rely on a questionnaire when I’m taking a history for anxiety. 

We also asked her how she explains anxiety to patients. I don’t know about you, Paul, but I’ve never really thought about explaining to patients why they have anxiety. 

Dr. Williams: I’ve done my best to try to normalize it, but I haven’t actually talked to patients about the evolutionary advantage of anxiety. 

Dr. Watto: She frames it to patients this way: As we were evolving, it was somewhat of an advantage to be hypervigilant, to have some anxiety and a healthy amount of fear so that you weren’t killed or eaten. But now, in the modern world, anxiety isn’t playing to our advantage. Anxiety is not making them safer; it’s making their lives worse. She explains to patients that she’s trying to help them overcome that. 

In terms of pharmacotherapy for anxiety, I always think about SSRIs as one of the first steps. Why not use an SNRI as first-line treatment?

Dr. Williams: I was glad we had this conversation because I feel, for whatever reason, a bit more comfortable treating depression than anxiety. In any case, Dr. Gold reaches for the SSRI first, in part because getting off an SNRI (for example, to switch to something else) can be absolutely miserable. The discontinuation effects can be severe enough to have to bridge some patients with a benzodiazepine to get them fully off the SNRI. So, an SNRI is not the first drug you should necessarily reach for. 

She thinks about using an SNRI if she has tried a couple of SSRIs that have been ineffective, or if the patient has a comorbid condition that might also benefit from the SNRI in the same way that you might use a tricyclic antidepressant in the patient with both migraines and anxiety. An SNRI might be a good medication to consider in the patient with neuropathic pain and anxiety but rarely as a first-line treatment, because if it doesn’t work out, getting the patient off that medication can be a challenge.

Dr. Watto: She mentioned venlafaxine as being especially difficult to get people off of. I’ve heard that bupropion should never be used in anxiety, and if you give it, you are a terrible doctor. What did we learn about that? 

Dr. Williams: It’s a drug I’ve hesitated to prescribe to patients with anxiety or even comorbid anxiety. I’m a little bit nervous for someone who has depression and anxiety to prescribe bupropion because it can be activating and make things worse. But Dr. Gold says that she has seen bupropion work for some patients so she will consider it, especially for patients who don’t want to gain weight, or for whom sexual side effects would be bothersome. So, it’s not always the wrong answer. In her expert opinion, you can try it and see how the patient responds, using shared decision-making and letting the patient know that they may not tolerate it as well as other medications. 

Dr. Watto: She sees a lot of younger people — students, working professionals — who do not want to gain weight, and that’s understandable. She will tell patients, “We can try bupropion, but if you get more anxious, we might not be able to continue it. We might have to use one of the first-line agents instead.” 

Dr. Williams: We talked about mirtazapine as well. She tells patients they are going to gain weight with it. You have to have that conversation with the patient to see whether that is something they are willing to tolerate. If so, mirtazapine might be worth a try, but you have to be upfront about the potential side effects and know what the medications you’re prescribing will do to patients. 

Dr. Watto: We asked her about benzodiazepines. For as-needed medication for people who are experiencing panic or anxiety attacks, she prescribes propranolol 10-20 mg twice a day as needed, which is a low dose. In primary care, we use higher doses for migraine prophylaxis. 

She uses propranolol because for some patients, it’s the physical symptoms of anxiety that are bothering them. She can calm down the physical symptoms with that and get by without needing to use a benzodiazepine. 

But what about thoughts that make people anxious? Can we change people’s thoughts with medication? 

Dr. Williams: Dr. Gold made the point that we can medicate away insomnia, for the most part. We can medicate away the physical symptoms of anxiety, which can be really bothersome. But we can’t medicate away thoughts and thought patterns. You can make patients feel better with medications, but you may not be able to get rid of the persistent bothersome thoughts. That’s where cognitive-behavioral therapy can be especially helpful. Most of these patients would benefit from therapy.

Dr. Watto: I completely agree with that. We talked about so many great things with Dr. Gold, but we can’t recap all of it here. Please click on this link to hear the full podcast episode. 
 

Dr. Watto is Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, Lewis Katz School of Medicine; Staff Physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He disclosed receiving income from The Curbsiders. The Curbsiders is an internal medicine podcast, in which three board-certified internists interview experts on clinically important topics. In a collaboration with Medscape, the Curbsiders share clinical pearls and practice-changing knowledge from selected podcasts.

A version of this article appeared on Medscape.com.

HOUSTON — Sleep may have a role in driving down rates of loneliness, especially among younger adults.

A study of nearly 2300 participants showed that better sleep health is associated with significantly lower levels of loneliness across ages and that the association is particularly strong in younger individuals.

The US Surgeon General has identified loneliness as “a major public health concern, linked to high rates of negative physical and mental health outcomes,” lead researcher Joseph Dzierzewski, PhD, vice president for research and scientific affairs at the National Sleep Foundation, told this news organization.

“Loneliness is an urgent public health crisis, and there is a pressing need for providers to better understand and treat it,” Dr. Dzierzewski said in a statement.

“Better sleep health might be connected to lower feelings of loneliness by empowering people to engage in social activities, reducing feelings of negative emotions and increasing the likelihood that people interpret interactions in a positive way,” he added.

The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies and recently published in an online supplement of the journal Sleep.
 

Rested, Connected

An American Psychiatric Association poll conducted earlier this year showed 30% of US adults reported feelings of loneliness at least once a week over the past year, and 10% reported feeling lonely every day.

Younger people are more likely to report feeling lonely, with 30% of Americans, aged 18-34 years, feeling lonely every day or several times a week.

While there is growing research identifying a relationship between loneliness and poor sleep in different age groups, few studies have explored ties between social and emotional loneliness and sleep health across the adult lifespan.

In the current study led by Dr. Dzierzewski, 2297 adults (mean age, 44 years; 51% male) completed a validated sleep health questionnaire and loneliness scale.

Linear regression analyses were used to examine the direct associations between sleep health, age, and loneliness. Moderation analyses tested whether the link between sleep health and loneliness differed by age.

On average, the total sleep score was 7.7 (range, 0-12), with higher scores indicating better multidimensional sleep health, and total loneliness scale score was 8.9 (out of 11), indicating moderate levels of loneliness.

Better sleep health and younger age were associated with significantly lower loneliness total scores and social and emotional loneliness subscale scores (all P < .001).

Age significantly moderated the association between sleep health and total (P < .001) and emotional loneliness scores (P < .001) but did not moderate the association between sleep health and social loneliness (P = .034). Better sleep health was associated with lower loneliness across ages, and this association was stronger at younger ages.

“Why younger adults might experience more sleep-related benefits to loneliness than older adults is unknown and intriguing — certainly worth further investigation,” Dr. Dzierzewski said in a conference statement.
 

Untapped Avenue

Promoting sleep health may be an “untapped avenue” to support efforts and programs that aim to reduce loneliness and increase engagement in all age groups but especially in younger ages, the researchers noted.

Future research should consider monitoring sleep health in programs or interventions that address loneliness, they added.

“Healthcare providers should be aware of the important link between sleep health and loneliness as both sleep and social connections are essential to health and well-being. When sitting across from patients, asking about both sleep health and loneliness might yield important insights into avenues for health promotion,” said Dr. Dzierzewski.

Michael Breus, PhD, clinical psychologist and founder of SleepDoctor.com, who wasn’t involved in the study, is not surprised by the results.

It makes sense that better sleep would lead to less feelings of loneliness, he told this news organization.

Research has shown that when someone is not sleeping well, they “give others a sense of unhappiness, which socially deflects new encounters or even encounters with friends. So social awareness and social initiation would appear to both be affected by sleep quality, therefore potentially leading, at least in part, to loneliness,” he said.

Support for the study was provided by the National Institute on Aging. Dr. Dzierzewski and Dr. Breus had no relevant disclosures.

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

HOUSTON — Sleep may have a role in driving down rates of loneliness, especially among younger adults.

A study of nearly 2300 participants showed that better sleep health is associated with significantly lower levels of loneliness across ages and that the association is particularly strong in younger individuals.

The US Surgeon General has identified loneliness as “a major public health concern, linked to high rates of negative physical and mental health outcomes,” lead researcher Joseph Dzierzewski, PhD, vice president for research and scientific affairs at the National Sleep Foundation, told this news organization.

“Loneliness is an urgent public health crisis, and there is a pressing need for providers to better understand and treat it,” Dr. Dzierzewski said in a statement.

“Better sleep health might be connected to lower feelings of loneliness by empowering people to engage in social activities, reducing feelings of negative emotions and increasing the likelihood that people interpret interactions in a positive way,” he added.

The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies and recently published in an online supplement of the journal Sleep.
 

Rested, Connected

An American Psychiatric Association poll conducted earlier this year showed 30% of US adults reported feelings of loneliness at least once a week over the past year, and 10% reported feeling lonely every day.

Younger people are more likely to report feeling lonely, with 30% of Americans, aged 18-34 years, feeling lonely every day or several times a week.

While there is growing research identifying a relationship between loneliness and poor sleep in different age groups, few studies have explored ties between social and emotional loneliness and sleep health across the adult lifespan.

In the current study led by Dr. Dzierzewski, 2297 adults (mean age, 44 years; 51% male) completed a validated sleep health questionnaire and loneliness scale.

Linear regression analyses were used to examine the direct associations between sleep health, age, and loneliness. Moderation analyses tested whether the link between sleep health and loneliness differed by age.

On average, the total sleep score was 7.7 (range, 0-12), with higher scores indicating better multidimensional sleep health, and total loneliness scale score was 8.9 (out of 11), indicating moderate levels of loneliness.

Better sleep health and younger age were associated with significantly lower loneliness total scores and social and emotional loneliness subscale scores (all P < .001).

Age significantly moderated the association between sleep health and total (P < .001) and emotional loneliness scores (P < .001) but did not moderate the association between sleep health and social loneliness (P = .034). Better sleep health was associated with lower loneliness across ages, and this association was stronger at younger ages.

“Why younger adults might experience more sleep-related benefits to loneliness than older adults is unknown and intriguing — certainly worth further investigation,” Dr. Dzierzewski said in a conference statement.
 

Untapped Avenue

Promoting sleep health may be an “untapped avenue” to support efforts and programs that aim to reduce loneliness and increase engagement in all age groups but especially in younger ages, the researchers noted.

Future research should consider monitoring sleep health in programs or interventions that address loneliness, they added.

“Healthcare providers should be aware of the important link between sleep health and loneliness as both sleep and social connections are essential to health and well-being. When sitting across from patients, asking about both sleep health and loneliness might yield important insights into avenues for health promotion,” said Dr. Dzierzewski.

Michael Breus, PhD, clinical psychologist and founder of SleepDoctor.com, who wasn’t involved in the study, is not surprised by the results.

It makes sense that better sleep would lead to less feelings of loneliness, he told this news organization.

Research has shown that when someone is not sleeping well, they “give others a sense of unhappiness, which socially deflects new encounters or even encounters with friends. So social awareness and social initiation would appear to both be affected by sleep quality, therefore potentially leading, at least in part, to loneliness,” he said.

Support for the study was provided by the National Institute on Aging. Dr. Dzierzewski and Dr. Breus had no relevant disclosures.

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

HOUSTON — Sleep may have a role in driving down rates of loneliness, especially among younger adults.

A study of nearly 2300 participants showed that better sleep health is associated with significantly lower levels of loneliness across ages and that the association is particularly strong in younger individuals.

The US Surgeon General has identified loneliness as “a major public health concern, linked to high rates of negative physical and mental health outcomes,” lead researcher Joseph Dzierzewski, PhD, vice president for research and scientific affairs at the National Sleep Foundation, told this news organization.

“Loneliness is an urgent public health crisis, and there is a pressing need for providers to better understand and treat it,” Dr. Dzierzewski said in a statement.

“Better sleep health might be connected to lower feelings of loneliness by empowering people to engage in social activities, reducing feelings of negative emotions and increasing the likelihood that people interpret interactions in a positive way,” he added.

The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies and recently published in an online supplement of the journal Sleep.
 

Rested, Connected

An American Psychiatric Association poll conducted earlier this year showed 30% of US adults reported feelings of loneliness at least once a week over the past year, and 10% reported feeling lonely every day.

Younger people are more likely to report feeling lonely, with 30% of Americans, aged 18-34 years, feeling lonely every day or several times a week.

While there is growing research identifying a relationship between loneliness and poor sleep in different age groups, few studies have explored ties between social and emotional loneliness and sleep health across the adult lifespan.

In the current study led by Dr. Dzierzewski, 2297 adults (mean age, 44 years; 51% male) completed a validated sleep health questionnaire and loneliness scale.

Linear regression analyses were used to examine the direct associations between sleep health, age, and loneliness. Moderation analyses tested whether the link between sleep health and loneliness differed by age.

On average, the total sleep score was 7.7 (range, 0-12), with higher scores indicating better multidimensional sleep health, and total loneliness scale score was 8.9 (out of 11), indicating moderate levels of loneliness.

Better sleep health and younger age were associated with significantly lower loneliness total scores and social and emotional loneliness subscale scores (all P < .001).

Age significantly moderated the association between sleep health and total (P < .001) and emotional loneliness scores (P < .001) but did not moderate the association between sleep health and social loneliness (P = .034). Better sleep health was associated with lower loneliness across ages, and this association was stronger at younger ages.

“Why younger adults might experience more sleep-related benefits to loneliness than older adults is unknown and intriguing — certainly worth further investigation,” Dr. Dzierzewski said in a conference statement.
 

Untapped Avenue

Promoting sleep health may be an “untapped avenue” to support efforts and programs that aim to reduce loneliness and increase engagement in all age groups but especially in younger ages, the researchers noted.

Future research should consider monitoring sleep health in programs or interventions that address loneliness, they added.

“Healthcare providers should be aware of the important link between sleep health and loneliness as both sleep and social connections are essential to health and well-being. When sitting across from patients, asking about both sleep health and loneliness might yield important insights into avenues for health promotion,” said Dr. Dzierzewski.

Michael Breus, PhD, clinical psychologist and founder of SleepDoctor.com, who wasn’t involved in the study, is not surprised by the results.

It makes sense that better sleep would lead to less feelings of loneliness, he told this news organization.

Research has shown that when someone is not sleeping well, they “give others a sense of unhappiness, which socially deflects new encounters or even encounters with friends. So social awareness and social initiation would appear to both be affected by sleep quality, therefore potentially leading, at least in part, to loneliness,” he said.

Support for the study was provided by the National Institute on Aging. Dr. Dzierzewski and Dr. Breus had no relevant disclosures.

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

TOPLINE:

Emergency department (ED) visits in the United States for suicide attempts and intentional self-harm show an increasing trend from 2011 to 2020, with visits being most common among adolescents and the largest increase in visits being seen in adults aged 65 years or older.

METHODOLOGY:

• This study used data from the National Hospital Ambulatory Medical Care Survey, an annual nationwide cross-sectional survey, to track trends in ED visits for suicide attempts and intentional self-harm in the United States from 2011 to 2020.
• Researchers identified visits for suicide attempts and intentional self-harm, along with diagnoses of any co-occurring mental health conditions, using discharge diagnosis codes or reason-for-visit codes.
• The focus was to identify the percentages of ED visits for suicide attempts and intentional self-harm, with analyses done per 100,000 persons and for changes possibly linked to the COVID-19 pandemic in 2019-2020.

TAKEAWAY:

• The number of ED visits owing to suicide attempts and intentional self-harm increased from 1.43 million in 2011-2012 to 5.37 million in 2019-2020 (average annual percent change, 19.5%; 95% confidence interval, 16.9-22.2).
• The rate of ED visits for suicide attempts and intentional self-harm was higher among adolescents and young adults, particularly women, and lower among children.
• Despite a surge in ED visits for self-harm, less than 16% included a mental health evaluation, with visits among patients with mood disorders decreasing by 5.5% annually and those among patients with drug-related disorders increasing by 6.8% annually.
• In 2019-2020, those aged 15-20 years had the highest rate of ED visits (1552 visits per 100,000 persons), with a significant increase seen across all age groups; the largest increase was among those aged 65 years or older.

IN PRACTICE:

“Given that suicide attempts are the single greatest risk factor for suicide, evidence-based management of individuals presenting to emergency departments with suicide attempts and intentional self-harm is a critical component of comprehensive suicide prevention strategies,” the authors wrote.

SOURCE:

The investigation, led by Tanner J. Bommersbach, MD, MPH, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, was published online in The American Journal of Psychiatry.

LIMITATIONS:

Visits for suicide attempts and intentional self-harm were identified based on discharge diagnostic and reason-for-visit codes, which may have led to an underestimation of visits for suicide attempts. ED visits for suicidal vs nonsuicidal self-injury could not be distinguished due to reliance on discharge diagnostic codes. Visits for suicidal ideation, which was not the focus of the study, may have been miscoded as suicide attempts and intentional self-harm.

DISCLOSURES:

No funding source was reported for the study. Some authors received funding grants from various institutions, and one author disclosed receiving honoraria for service as a review committee member and serving as a stakeholder/consultant and as an advisory committee member for some institutes and agencies.

A version of this article appeared on Medscape.com.

TOPLINE:

Emergency department (ED) visits in the United States for suicide attempts and intentional self-harm show an increasing trend from 2011 to 2020, with visits being most common among adolescents and the largest increase in visits being seen in adults aged 65 years or older.

METHODOLOGY:

• This study used data from the National Hospital Ambulatory Medical Care Survey, an annual nationwide cross-sectional survey, to track trends in ED visits for suicide attempts and intentional self-harm in the United States from 2011 to 2020.
• Researchers identified visits for suicide attempts and intentional self-harm, along with diagnoses of any co-occurring mental health conditions, using discharge diagnosis codes or reason-for-visit codes.
• The focus was to identify the percentages of ED visits for suicide attempts and intentional self-harm, with analyses done per 100,000 persons and for changes possibly linked to the COVID-19 pandemic in 2019-2020.

TAKEAWAY:

• The number of ED visits owing to suicide attempts and intentional self-harm increased from 1.43 million in 2011-2012 to 5.37 million in 2019-2020 (average annual percent change, 19.5%; 95% confidence interval, 16.9-22.2).
• The rate of ED visits for suicide attempts and intentional self-harm was higher among adolescents and young adults, particularly women, and lower among children.
• Despite a surge in ED visits for self-harm, less than 16% included a mental health evaluation, with visits among patients with mood disorders decreasing by 5.5% annually and those among patients with drug-related disorders increasing by 6.8% annually.
• In 2019-2020, those aged 15-20 years had the highest rate of ED visits (1552 visits per 100,000 persons), with a significant increase seen across all age groups; the largest increase was among those aged 65 years or older.

IN PRACTICE:

“Given that suicide attempts are the single greatest risk factor for suicide, evidence-based management of individuals presenting to emergency departments with suicide attempts and intentional self-harm is a critical component of comprehensive suicide prevention strategies,” the authors wrote.

SOURCE:

The investigation, led by Tanner J. Bommersbach, MD, MPH, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, was published online in The American Journal of Psychiatry.

LIMITATIONS:

Visits for suicide attempts and intentional self-harm were identified based on discharge diagnostic and reason-for-visit codes, which may have led to an underestimation of visits for suicide attempts. ED visits for suicidal vs nonsuicidal self-injury could not be distinguished due to reliance on discharge diagnostic codes. Visits for suicidal ideation, which was not the focus of the study, may have been miscoded as suicide attempts and intentional self-harm.

DISCLOSURES:

No funding source was reported for the study. Some authors received funding grants from various institutions, and one author disclosed receiving honoraria for service as a review committee member and serving as a stakeholder/consultant and as an advisory committee member for some institutes and agencies.

A version of this article appeared on Medscape.com.

TOPLINE:

Emergency department (ED) visits in the United States for suicide attempts and intentional self-harm show an increasing trend from 2011 to 2020, with visits being most common among adolescents and the largest increase in visits being seen in adults aged 65 years or older.

METHODOLOGY:

• This study used data from the National Hospital Ambulatory Medical Care Survey, an annual nationwide cross-sectional survey, to track trends in ED visits for suicide attempts and intentional self-harm in the United States from 2011 to 2020.
• Researchers identified visits for suicide attempts and intentional self-harm, along with diagnoses of any co-occurring mental health conditions, using discharge diagnosis codes or reason-for-visit codes.
• The focus was to identify the percentages of ED visits for suicide attempts and intentional self-harm, with analyses done per 100,000 persons and for changes possibly linked to the COVID-19 pandemic in 2019-2020.

TAKEAWAY:

• The number of ED visits owing to suicide attempts and intentional self-harm increased from 1.43 million in 2011-2012 to 5.37 million in 2019-2020 (average annual percent change, 19.5%; 95% confidence interval, 16.9-22.2).
• The rate of ED visits for suicide attempts and intentional self-harm was higher among adolescents and young adults, particularly women, and lower among children.
• Despite a surge in ED visits for self-harm, less than 16% included a mental health evaluation, with visits among patients with mood disorders decreasing by 5.5% annually and those among patients with drug-related disorders increasing by 6.8% annually.
• In 2019-2020, those aged 15-20 years had the highest rate of ED visits (1552 visits per 100,000 persons), with a significant increase seen across all age groups; the largest increase was among those aged 65 years or older.

IN PRACTICE:

“Given that suicide attempts are the single greatest risk factor for suicide, evidence-based management of individuals presenting to emergency departments with suicide attempts and intentional self-harm is a critical component of comprehensive suicide prevention strategies,” the authors wrote.

SOURCE:

The investigation, led by Tanner J. Bommersbach, MD, MPH, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, was published online in The American Journal of Psychiatry.

LIMITATIONS:

Visits for suicide attempts and intentional self-harm were identified based on discharge diagnostic and reason-for-visit codes, which may have led to an underestimation of visits for suicide attempts. ED visits for suicidal vs nonsuicidal self-injury could not be distinguished due to reliance on discharge diagnostic codes. Visits for suicidal ideation, which was not the focus of the study, may have been miscoded as suicide attempts and intentional self-harm.

DISCLOSURES:

No funding source was reported for the study. Some authors received funding grants from various institutions, and one author disclosed receiving honoraria for service as a review committee member and serving as a stakeholder/consultant and as an advisory committee member for some institutes and agencies.

A version of this article appeared on Medscape.com.