Mental Health

A machine-learning risk model that incorporates childhood characteristics can predict development of bipolar disorder up to a decade later, according to investigators.

This is the first quantitative approach to predict bipolar disorder, offering sensitivity and specificity of 75% and 76%, respectively, reported lead author Mai Uchida, MD, director of the pediatric depression program at Massachusetts General Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, and colleagues. With further development, the model could be used to identify at-risk children via electronic medical records, enabling earlier monitoring and intervention.

“Although longitudinal studies have found the prognosis of early-onset mood disorders to be unfavorable, research has also shown there are effective treatments and therapies that could significantly alleviate the patients’ and their families’ struggles from the diagnoses,” the investigators wrote in the Journal of Psychiatric Research. “Thus, early identification of the risks and interventions for early symptoms of pediatric mood disorders is crucial.”

To this end, Dr. Uchida and colleagues teamed up with the Gabrieli Lab at MIT, who have published extensively in the realm of neurodevelopment. They sourced data from 492 children, 6-18 years at baseline, who were involved in two longitudinal case-control family studies focused on ADHD. Inputs included psychometric scales, structured diagnostic interviews, social and cognitive functioning assessments, and sociodemographic data.

At 10-year follow-up, 10% of these children had developed bipolar disorder, a notably higher rate than the 3%-4% prevalence in the general population.

“This is a population that’s overrepresented,” Dr. Uchida said in an interview.

She offered two primary reasons for this: First, the families involved in the study were probably willing to be followed for 10 years because they had ongoing concerns about their child’s mental health. Second, the studies enrolled children diagnosed with ADHD, a condition associated with increased risk of bipolar disorder.

Using machine learning algorithms that processed the baseline data while accounting for the skewed distribution, the investigators were able to predict which of the children in the population would go on to develop bipolar disorder. The final model offered a sensitivity of 75%, a specificity of 76%, and an area under the receiver operating characteristic curve of 75%.

“To the best of our knowledge, this represents the first study using machine-learning algorithms for this purpose in pediatric psychiatry,” the investigators wrote.
 

Integrating models into electronic medical records

In the future, this model, or one like it, could be incorporated into software that automatically analyzes electronic medical records and notifies physicians about high-risk patients, Dr. Uchida predicted.

“Not all patients would connect to intervention,” she said. “Maybe it just means that you invite them in for a visit, or you observe them a little bit more carefully. I think that’s where we are hoping that machine learning and medical practice will go.”

When asked about the potential bias posed by psychiatric evaluation, compared with something like blood work results, Dr. Uchida suggested that this subjectivity can be overcome.

“I’m not entirely bothered by that,” she said, offering a list of objective data points that could be harvested from records, such as number of referrals, medications, and hospitalizations. Narrative text in medical records could also be analyzed, she said, potentially detecting key words that are more often associated with high-risk patients.

“Risk prediction is never going to be 100% accurate,” Dr. Uchida said. “But I do think that there will be things [in electronic medical records] that could guide how worried we should be, or how quickly we should intervene.”
 

Opening doors to personalized care

Martin Gignac, MD, chief of psychiatry at Montreal Children’s Hospital and associate professor at McGill University, Montreal, said the present study offers further support for the existence of pediatric-onset bipolar disorder, which “remains controversial” despite “solid evidence.”

“I’m impressed that we have 10-year-long longitudinal follow-up studies that corroborate the importance of this disorder, and show strong predictors of who is at risk,” Dr. Gignac said in an interview. “Clinicians treating a pediatric population should be aware that some of those children with mental health problems might have severe mental health problems, and you have to have the appropriate tools to screen them.”

Advanced tools like the one developed by Dr. Uchida and colleagues should lead to more personalized care, he said.

“We’re going to be able to define what your individual risk is, and maybe most importantly, what you can do to prevent the development of certain disorders,” Dr. Gignac said. “Are there any risks that are dynamic in nature, and that we can act upon? Exposure to stress, for example.”

While more work is needed to bring machine learning into daily psychiatric practice, Dr. Gignac concluded on an optimistic note.

“These instruments should translate from research into clinical practice in order to make difference for the patients we care for,” he said. “This is the type of hope that I hold – that it’s going to be applicable in clinical practice, hopefully, in the near future.”

The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Gignac disclosed no relevant competing interests.

A machine-learning risk model that incorporates childhood characteristics can predict development of bipolar disorder up to a decade later, according to investigators.

This is the first quantitative approach to predict bipolar disorder, offering sensitivity and specificity of 75% and 76%, respectively, reported lead author Mai Uchida, MD, director of the pediatric depression program at Massachusetts General Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, and colleagues. With further development, the model could be used to identify at-risk children via electronic medical records, enabling earlier monitoring and intervention.

“Although longitudinal studies have found the prognosis of early-onset mood disorders to be unfavorable, research has also shown there are effective treatments and therapies that could significantly alleviate the patients’ and their families’ struggles from the diagnoses,” the investigators wrote in the Journal of Psychiatric Research. “Thus, early identification of the risks and interventions for early symptoms of pediatric mood disorders is crucial.”

To this end, Dr. Uchida and colleagues teamed up with the Gabrieli Lab at MIT, who have published extensively in the realm of neurodevelopment. They sourced data from 492 children, 6-18 years at baseline, who were involved in two longitudinal case-control family studies focused on ADHD. Inputs included psychometric scales, structured diagnostic interviews, social and cognitive functioning assessments, and sociodemographic data.

At 10-year follow-up, 10% of these children had developed bipolar disorder, a notably higher rate than the 3%-4% prevalence in the general population.

“This is a population that’s overrepresented,” Dr. Uchida said in an interview.

She offered two primary reasons for this: First, the families involved in the study were probably willing to be followed for 10 years because they had ongoing concerns about their child’s mental health. Second, the studies enrolled children diagnosed with ADHD, a condition associated with increased risk of bipolar disorder.

Using machine learning algorithms that processed the baseline data while accounting for the skewed distribution, the investigators were able to predict which of the children in the population would go on to develop bipolar disorder. The final model offered a sensitivity of 75%, a specificity of 76%, and an area under the receiver operating characteristic curve of 75%.

“To the best of our knowledge, this represents the first study using machine-learning algorithms for this purpose in pediatric psychiatry,” the investigators wrote.
 

Integrating models into electronic medical records

In the future, this model, or one like it, could be incorporated into software that automatically analyzes electronic medical records and notifies physicians about high-risk patients, Dr. Uchida predicted.

“Not all patients would connect to intervention,” she said. “Maybe it just means that you invite them in for a visit, or you observe them a little bit more carefully. I think that’s where we are hoping that machine learning and medical practice will go.”

When asked about the potential bias posed by psychiatric evaluation, compared with something like blood work results, Dr. Uchida suggested that this subjectivity can be overcome.

“I’m not entirely bothered by that,” she said, offering a list of objective data points that could be harvested from records, such as number of referrals, medications, and hospitalizations. Narrative text in medical records could also be analyzed, she said, potentially detecting key words that are more often associated with high-risk patients.

“Risk prediction is never going to be 100% accurate,” Dr. Uchida said. “But I do think that there will be things [in electronic medical records] that could guide how worried we should be, or how quickly we should intervene.”
 

Opening doors to personalized care

Martin Gignac, MD, chief of psychiatry at Montreal Children’s Hospital and associate professor at McGill University, Montreal, said the present study offers further support for the existence of pediatric-onset bipolar disorder, which “remains controversial” despite “solid evidence.”

“I’m impressed that we have 10-year-long longitudinal follow-up studies that corroborate the importance of this disorder, and show strong predictors of who is at risk,” Dr. Gignac said in an interview. “Clinicians treating a pediatric population should be aware that some of those children with mental health problems might have severe mental health problems, and you have to have the appropriate tools to screen them.”

Advanced tools like the one developed by Dr. Uchida and colleagues should lead to more personalized care, he said.

“We’re going to be able to define what your individual risk is, and maybe most importantly, what you can do to prevent the development of certain disorders,” Dr. Gignac said. “Are there any risks that are dynamic in nature, and that we can act upon? Exposure to stress, for example.”

While more work is needed to bring machine learning into daily psychiatric practice, Dr. Gignac concluded on an optimistic note.

“These instruments should translate from research into clinical practice in order to make difference for the patients we care for,” he said. “This is the type of hope that I hold – that it’s going to be applicable in clinical practice, hopefully, in the near future.”

The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Gignac disclosed no relevant competing interests.

A machine-learning risk model that incorporates childhood characteristics can predict development of bipolar disorder up to a decade later, according to investigators.

This is the first quantitative approach to predict bipolar disorder, offering sensitivity and specificity of 75% and 76%, respectively, reported lead author Mai Uchida, MD, director of the pediatric depression program at Massachusetts General Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, and colleagues. With further development, the model could be used to identify at-risk children via electronic medical records, enabling earlier monitoring and intervention.

“Although longitudinal studies have found the prognosis of early-onset mood disorders to be unfavorable, research has also shown there are effective treatments and therapies that could significantly alleviate the patients’ and their families’ struggles from the diagnoses,” the investigators wrote in the Journal of Psychiatric Research. “Thus, early identification of the risks and interventions for early symptoms of pediatric mood disorders is crucial.”

To this end, Dr. Uchida and colleagues teamed up with the Gabrieli Lab at MIT, who have published extensively in the realm of neurodevelopment. They sourced data from 492 children, 6-18 years at baseline, who were involved in two longitudinal case-control family studies focused on ADHD. Inputs included psychometric scales, structured diagnostic interviews, social and cognitive functioning assessments, and sociodemographic data.

At 10-year follow-up, 10% of these children had developed bipolar disorder, a notably higher rate than the 3%-4% prevalence in the general population.

“This is a population that’s overrepresented,” Dr. Uchida said in an interview.

She offered two primary reasons for this: First, the families involved in the study were probably willing to be followed for 10 years because they had ongoing concerns about their child’s mental health. Second, the studies enrolled children diagnosed with ADHD, a condition associated with increased risk of bipolar disorder.

Using machine learning algorithms that processed the baseline data while accounting for the skewed distribution, the investigators were able to predict which of the children in the population would go on to develop bipolar disorder. The final model offered a sensitivity of 75%, a specificity of 76%, and an area under the receiver operating characteristic curve of 75%.

“To the best of our knowledge, this represents the first study using machine-learning algorithms for this purpose in pediatric psychiatry,” the investigators wrote.
 

Integrating models into electronic medical records

In the future, this model, or one like it, could be incorporated into software that automatically analyzes electronic medical records and notifies physicians about high-risk patients, Dr. Uchida predicted.

“Not all patients would connect to intervention,” she said. “Maybe it just means that you invite them in for a visit, or you observe them a little bit more carefully. I think that’s where we are hoping that machine learning and medical practice will go.”

When asked about the potential bias posed by psychiatric evaluation, compared with something like blood work results, Dr. Uchida suggested that this subjectivity can be overcome.

“I’m not entirely bothered by that,” she said, offering a list of objective data points that could be harvested from records, such as number of referrals, medications, and hospitalizations. Narrative text in medical records could also be analyzed, she said, potentially detecting key words that are more often associated with high-risk patients.

“Risk prediction is never going to be 100% accurate,” Dr. Uchida said. “But I do think that there will be things [in electronic medical records] that could guide how worried we should be, or how quickly we should intervene.”
 

Opening doors to personalized care

Martin Gignac, MD, chief of psychiatry at Montreal Children’s Hospital and associate professor at McGill University, Montreal, said the present study offers further support for the existence of pediatric-onset bipolar disorder, which “remains controversial” despite “solid evidence.”

“I’m impressed that we have 10-year-long longitudinal follow-up studies that corroborate the importance of this disorder, and show strong predictors of who is at risk,” Dr. Gignac said in an interview. “Clinicians treating a pediatric population should be aware that some of those children with mental health problems might have severe mental health problems, and you have to have the appropriate tools to screen them.”

Advanced tools like the one developed by Dr. Uchida and colleagues should lead to more personalized care, he said.

“We’re going to be able to define what your individual risk is, and maybe most importantly, what you can do to prevent the development of certain disorders,” Dr. Gignac said. “Are there any risks that are dynamic in nature, and that we can act upon? Exposure to stress, for example.”

While more work is needed to bring machine learning into daily psychiatric practice, Dr. Gignac concluded on an optimistic note.

“These instruments should translate from research into clinical practice in order to make difference for the patients we care for,” he said. “This is the type of hope that I hold – that it’s going to be applicable in clinical practice, hopefully, in the near future.”

The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Gignac disclosed no relevant competing interests.

VIENNA – Inpatient treatment for major depressive disorder (MDD) can lead to brain connectivity increases that are associated with degree of symptom improvement, new research suggests.

In a “repeat” MRI study, adult participants with MDD had significantly lower brain connectivity compared with their healthy peers at baseline – but showed significant improvement at the 6-week follow-up. These improvements were associated with decreases in symptom severity, independent of whether they received electroconvulsive therapy (ECT) or other treatment modalities.

“This means that the brain structure of patients with serious clinical depression is not as fixed as we thought, and we can improve brain structure within a short time frame [of] around 6 weeks,” lead author Jonathan Repple, MD, now professor of predictive psychiatry at the University of Frankfurt, Germany, said in a release.

“This gives hope to patients who believe nothing can change and they have to live with a disease forever because it is ‘set in stone’ in their brain,” he added.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Easily understandable picture’

Dr. Repple said in an interview that the investigators “were surprised to see how plastic” the brain could be.

“I’ve done a lot of imaging studies in the past where we looked at differences in depression vs. healthy controls, and then maybe had tiny effects. But we’ve never seen such a clear and easily understandable picture, where we see a deficit at the beginning and then a significant increase in whatever biomarker we were looking at, that even correlated with how successful the treatment was,” he said.

Dr. Repple noted that “this is the thing everyone is looking for when we’re talking about a biomarker: That we see this exact pattern” – and it is why they are so excited about the results.

However, he cautioned that the study included a “small sample” and the results need to be independently replicated.

“If this can be replicated, this might be a very good target for future intervention studies,” Dr. Repple said.

The investigators noted that altered brain structural connectivity has been implicated before in the pathophysiology of MDD.

However, it is not clear whether these changes are stable over time and indicate a biological predisposition, or are markers of current disease severity and can be altered by effective treatment.

To investigate further, the researchers used gray matter T1-weighted MRI to define nodes in the brain and diffusion-weighted imaging (DWI)-based tractography to determine connections between the nodes, to create a structural connectome or white matter network.

They performed assessments at baseline and at 6 weeks’ follow-up in 123 participants diagnosed with current MDD and receiving inpatient treatment, and 55 participants who acted as the healthy controls group.

Among the patients with MDD, 56 were treated with ECT and 67 received other antidepressant care, including psychological therapy or medications. Some patients had received all three treatment modalities.
 

Significant interactions

Results showed a significant interaction by group and time between the baseline and 6-week follow-up assessments (P < .05).

This was partly driven by the MDD group having a significantly lower connectivity strength at baseline than the healthy controls group (P < .05).

It was also partly driven by patients showing a significant improvement in connectivity strength between the baseline and follow-up assessments (P < .05), a pattern that was not seen in the nonpatients.

This increase in connectivity strength was associated with a significant decrease in depression symptom severity (P < .05). This was independent of the treatment modality, indicating that it was not linked to the use of ECT.

Dr. Repple acknowledged the relatively short follow-up period of the study, and added that he is not aware of longitudinal studies of the structural connectome with a longer follow-up.

He pointed out that the structural connectivity of the brain decreases with age, but there have been no studies that have assessed patients with depression and “measured the same person again after 2, 4, 6, or 8 years.”

Dr. Repple reported that the investigators will be following up with their participants, “so hopefully in a few years we’ll have more information on that.

“One thing I also need to stress is that, when we’re looking at the MRI brain scans, we see an increase in connectivity strength, but we really can’t say what the molecular mechanisms behind it are,” he said. “This is a black box for us.”
 

Several unanswered questions

Commenting in the release, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said this was a “very interesting and difficult study to perform.”

However, Dr. Ruhe, who was not involved in the research, told this news organization that it is “very difficult to connect the lack of brain connectivity to the patient symptomatology because there is a huge gap between them.”

The problem is that, despite “lots of evidence” that they are effective, “we currently don’t know how antidepressant therapies work” in terms of their underlying mechanisms of action, he said.

“We think that these types of therapies all modulate the plasticity of the brain,” said Dr. Ruhe. “What this study showed is there are changes that you can detect even in 6 weeks,” although they may have been observed even sooner with a shorter follow-up.

He noted that big questions are whether the change is specific to the treatment given, and “can you modulate different brain network dysfunctions with different treatments?”

Moreover, he wondered if a brain scan could indicate which type of treatment should be used. “This is, of course, very new and very challenging, and we don’t know yet, but we should be pursuing this,” Dr. Ruhe said.

Another question is whether or not the brain connectivity changes shown in the study represent a persistent change – “and whether this is a persistent change that is associated with a consistent and persistent relief of depression.

“Again, this is something that needs to be followed up,” said Dr. Ruhe.

No funding was declared. The study authors and Dr. Ruhe report no relevant financial relationships.

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

VIENNA – Inpatient treatment for major depressive disorder (MDD) can lead to brain connectivity increases that are associated with degree of symptom improvement, new research suggests.

In a “repeat” MRI study, adult participants with MDD had significantly lower brain connectivity compared with their healthy peers at baseline – but showed significant improvement at the 6-week follow-up. These improvements were associated with decreases in symptom severity, independent of whether they received electroconvulsive therapy (ECT) or other treatment modalities.

“This means that the brain structure of patients with serious clinical depression is not as fixed as we thought, and we can improve brain structure within a short time frame [of] around 6 weeks,” lead author Jonathan Repple, MD, now professor of predictive psychiatry at the University of Frankfurt, Germany, said in a release.

“This gives hope to patients who believe nothing can change and they have to live with a disease forever because it is ‘set in stone’ in their brain,” he added.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Easily understandable picture’

Dr. Repple said in an interview that the investigators “were surprised to see how plastic” the brain could be.

“I’ve done a lot of imaging studies in the past where we looked at differences in depression vs. healthy controls, and then maybe had tiny effects. But we’ve never seen such a clear and easily understandable picture, where we see a deficit at the beginning and then a significant increase in whatever biomarker we were looking at, that even correlated with how successful the treatment was,” he said.

Dr. Repple noted that “this is the thing everyone is looking for when we’re talking about a biomarker: That we see this exact pattern” – and it is why they are so excited about the results.

However, he cautioned that the study included a “small sample” and the results need to be independently replicated.

“If this can be replicated, this might be a very good target for future intervention studies,” Dr. Repple said.

The investigators noted that altered brain structural connectivity has been implicated before in the pathophysiology of MDD.

However, it is not clear whether these changes are stable over time and indicate a biological predisposition, or are markers of current disease severity and can be altered by effective treatment.

To investigate further, the researchers used gray matter T1-weighted MRI to define nodes in the brain and diffusion-weighted imaging (DWI)-based tractography to determine connections between the nodes, to create a structural connectome or white matter network.

They performed assessments at baseline and at 6 weeks’ follow-up in 123 participants diagnosed with current MDD and receiving inpatient treatment, and 55 participants who acted as the healthy controls group.

Among the patients with MDD, 56 were treated with ECT and 67 received other antidepressant care, including psychological therapy or medications. Some patients had received all three treatment modalities.
 

Significant interactions

Results showed a significant interaction by group and time between the baseline and 6-week follow-up assessments (P < .05).

This was partly driven by the MDD group having a significantly lower connectivity strength at baseline than the healthy controls group (P < .05).

It was also partly driven by patients showing a significant improvement in connectivity strength between the baseline and follow-up assessments (P < .05), a pattern that was not seen in the nonpatients.

This increase in connectivity strength was associated with a significant decrease in depression symptom severity (P < .05). This was independent of the treatment modality, indicating that it was not linked to the use of ECT.

Dr. Repple acknowledged the relatively short follow-up period of the study, and added that he is not aware of longitudinal studies of the structural connectome with a longer follow-up.

He pointed out that the structural connectivity of the brain decreases with age, but there have been no studies that have assessed patients with depression and “measured the same person again after 2, 4, 6, or 8 years.”

Dr. Repple reported that the investigators will be following up with their participants, “so hopefully in a few years we’ll have more information on that.

“One thing I also need to stress is that, when we’re looking at the MRI brain scans, we see an increase in connectivity strength, but we really can’t say what the molecular mechanisms behind it are,” he said. “This is a black box for us.”
 

Several unanswered questions

Commenting in the release, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said this was a “very interesting and difficult study to perform.”

However, Dr. Ruhe, who was not involved in the research, told this news organization that it is “very difficult to connect the lack of brain connectivity to the patient symptomatology because there is a huge gap between them.”

The problem is that, despite “lots of evidence” that they are effective, “we currently don’t know how antidepressant therapies work” in terms of their underlying mechanisms of action, he said.

“We think that these types of therapies all modulate the plasticity of the brain,” said Dr. Ruhe. “What this study showed is there are changes that you can detect even in 6 weeks,” although they may have been observed even sooner with a shorter follow-up.

He noted that big questions are whether the change is specific to the treatment given, and “can you modulate different brain network dysfunctions with different treatments?”

Moreover, he wondered if a brain scan could indicate which type of treatment should be used. “This is, of course, very new and very challenging, and we don’t know yet, but we should be pursuing this,” Dr. Ruhe said.

Another question is whether or not the brain connectivity changes shown in the study represent a persistent change – “and whether this is a persistent change that is associated with a consistent and persistent relief of depression.

“Again, this is something that needs to be followed up,” said Dr. Ruhe.

No funding was declared. The study authors and Dr. Ruhe report no relevant financial relationships.

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

VIENNA – Inpatient treatment for major depressive disorder (MDD) can lead to brain connectivity increases that are associated with degree of symptom improvement, new research suggests.

In a “repeat” MRI study, adult participants with MDD had significantly lower brain connectivity compared with their healthy peers at baseline – but showed significant improvement at the 6-week follow-up. These improvements were associated with decreases in symptom severity, independent of whether they received electroconvulsive therapy (ECT) or other treatment modalities.

“This means that the brain structure of patients with serious clinical depression is not as fixed as we thought, and we can improve brain structure within a short time frame [of] around 6 weeks,” lead author Jonathan Repple, MD, now professor of predictive psychiatry at the University of Frankfurt, Germany, said in a release.

“This gives hope to patients who believe nothing can change and they have to live with a disease forever because it is ‘set in stone’ in their brain,” he added.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Easily understandable picture’

Dr. Repple said in an interview that the investigators “were surprised to see how plastic” the brain could be.

“I’ve done a lot of imaging studies in the past where we looked at differences in depression vs. healthy controls, and then maybe had tiny effects. But we’ve never seen such a clear and easily understandable picture, where we see a deficit at the beginning and then a significant increase in whatever biomarker we were looking at, that even correlated with how successful the treatment was,” he said.

Dr. Repple noted that “this is the thing everyone is looking for when we’re talking about a biomarker: That we see this exact pattern” – and it is why they are so excited about the results.

However, he cautioned that the study included a “small sample” and the results need to be independently replicated.

“If this can be replicated, this might be a very good target for future intervention studies,” Dr. Repple said.

The investigators noted that altered brain structural connectivity has been implicated before in the pathophysiology of MDD.

However, it is not clear whether these changes are stable over time and indicate a biological predisposition, or are markers of current disease severity and can be altered by effective treatment.

To investigate further, the researchers used gray matter T1-weighted MRI to define nodes in the brain and diffusion-weighted imaging (DWI)-based tractography to determine connections between the nodes, to create a structural connectome or white matter network.

They performed assessments at baseline and at 6 weeks’ follow-up in 123 participants diagnosed with current MDD and receiving inpatient treatment, and 55 participants who acted as the healthy controls group.

Among the patients with MDD, 56 were treated with ECT and 67 received other antidepressant care, including psychological therapy or medications. Some patients had received all three treatment modalities.
 

Significant interactions

Results showed a significant interaction by group and time between the baseline and 6-week follow-up assessments (P < .05).

This was partly driven by the MDD group having a significantly lower connectivity strength at baseline than the healthy controls group (P < .05).

It was also partly driven by patients showing a significant improvement in connectivity strength between the baseline and follow-up assessments (P < .05), a pattern that was not seen in the nonpatients.

This increase in connectivity strength was associated with a significant decrease in depression symptom severity (P < .05). This was independent of the treatment modality, indicating that it was not linked to the use of ECT.

Dr. Repple acknowledged the relatively short follow-up period of the study, and added that he is not aware of longitudinal studies of the structural connectome with a longer follow-up.

He pointed out that the structural connectivity of the brain decreases with age, but there have been no studies that have assessed patients with depression and “measured the same person again after 2, 4, 6, or 8 years.”

Dr. Repple reported that the investigators will be following up with their participants, “so hopefully in a few years we’ll have more information on that.

“One thing I also need to stress is that, when we’re looking at the MRI brain scans, we see an increase in connectivity strength, but we really can’t say what the molecular mechanisms behind it are,” he said. “This is a black box for us.”
 

Several unanswered questions

Commenting in the release, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said this was a “very interesting and difficult study to perform.”

However, Dr. Ruhe, who was not involved in the research, told this news organization that it is “very difficult to connect the lack of brain connectivity to the patient symptomatology because there is a huge gap between them.”

The problem is that, despite “lots of evidence” that they are effective, “we currently don’t know how antidepressant therapies work” in terms of their underlying mechanisms of action, he said.

“We think that these types of therapies all modulate the plasticity of the brain,” said Dr. Ruhe. “What this study showed is there are changes that you can detect even in 6 weeks,” although they may have been observed even sooner with a shorter follow-up.

He noted that big questions are whether the change is specific to the treatment given, and “can you modulate different brain network dysfunctions with different treatments?”

Moreover, he wondered if a brain scan could indicate which type of treatment should be used. “This is, of course, very new and very challenging, and we don’t know yet, but we should be pursuing this,” Dr. Ruhe said.

Another question is whether or not the brain connectivity changes shown in the study represent a persistent change – “and whether this is a persistent change that is associated with a consistent and persistent relief of depression.

“Again, this is something that needs to be followed up,” said Dr. Ruhe.

No funding was declared. The study authors and Dr. Ruhe report no relevant financial relationships.

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

The Canadian Paediatric Society (CPS) has issued a position statement on the diagnosis of anxiety disorders in children and youth. The organization aims to “offer evidence-informed guidance to support pediatric health care providers making decisions around the care of children and adolescents with these conditions.”

“It’s been a long time coming,” lead author Benjamin Klein, MD, assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont., told this news organization. The target audience for the documents includes community pediatricians, subspecialists, family doctors, and nurse practitioners. “There was a great demand from that audience for a position statement, for guidance, obviously in the backdrop of rising child and adolescent mental health incidence over the years and of course COVID,” said Dr. Klein.

The statement was published on the CPS website.
 

‘A comprehensive approach’

Although many other guidelines on this topic are available, it was important to have a Canadian document, said Dr. Klein. “Obviously, there’s going to be a great deal of overlap with European or American guidelines, but it’s just kind of assumed that people want specifically Canadian content. ... Physicians want to know that they’re practicing within a standard of care in Canada.” Dr. Klein is medical director of the Lansdowne Children’s Centre, Brantford, Ont., which provides help for children with communication, developmental, and physical special needs across Ontario.

Anxiety disorders are the most common mental disorders among children and adolescents in Canada, according to the position statement. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) groups these disorders into separation anxiety disorder, selective mutism, specific phobia, social anxiety disorder (social phobia), panic disorder, agoraphobia, and generalized anxiety disorder.

Distinguishing normal, age-appropriate anxiety from anxiety disorder, while also recognizing other comorbidities, is complicated, said Dr. Klein. “Anxiety is one possible diagnosis or feature, and children with mental health and developmental problems often present with a number of problems. Anxiety may be one of them, but if it’s one of them, it may not be the main driver. So, a comprehensive approach is needed ... combining the medical model with biopsychosocial thinking to give a better picture of anxiety in the context of anything else that may be contributing to a presentation.”

The statement outlines recommendations for anxiety assessment, starting with a screening questionnaire such as the Screen for Child Anxiety Related Disorders (SCARED), which is completed by parents and children, to assess symptom severity. Standardized measures for medical, mental health, and developmental histories are available on the CPS website.

The document next recommends an interview about presenting concerns (such as sleep problems or school difficulties), inciting events, and parent-child interactions. The process includes confidential, nonjudgmental interviews with adolescents using a history-taking tool such as HEEADSSS (Home, Education/Employment, Eating, Activities, Drugs, Sexuality, Suicide/Mental Health, and Safety).

“The diagnosis and treatment of anxiety disorders kind of sounds simple if you just read about it as an isolated thing, but the reality is ... there’s no MRI. It’s detective work,” said Dr. Klein. Clinicians must distinguish between normal anxiety, situational anxiety, and specific anxiety disorder, he added. He usually allows 90 minutes for an anxiety assessment, partly to gain the patient’s trust. “These are sensitive issues. It’s common that people don’t trust a diagnosis if you haven’t spent enough time with them. That relational care piece just needs to be there, or people aren’t going to buy in.”

The CPS position statement was reviewed and endorsed by the Canadian Academy of Child and Adolescent Psychiatry.
 

Methodology unclear

Joanna Henderson, MD, professor of psychiatry at the University of Toronto and director of the Margaret and Wallace McCain Centre for Child, Youth, and Family Mental Health at the Centre for Addiction and Mental Health, Toronto, said that the guidelines have been released at an important time. “Conversations about mental health have become more common, and many children, youth, and families are reaching out for support. It is essential that health care professionals be equipped with accessible information about practices to provide appropriate care. These guidelines support that vision.”

It would be helpful to know more about the methods used to arrive at the recommendations, however, said Dr. Henderson. “It is critical that health care providers be guided by evidence-based guidelines that adhere to criteria for establishing high-quality guidelines. Because the authors did not provide information about their methods, I am not able to provide a comment about the quality of their guidelines. There are established approaches for evaluating quality, and I would encourage the authors to publish as a supplement to this article their methods, including in reference to the Appraisal of Guidelines for Research and Evaluation (AGREE II) checklist.”

In the absence of readily available information about methods, she said, “clinicians are encouraged to use guidelines from sources that provide information about the guideline development process and include quality appraisal,” such as the UK National Institute for Health and Care Excellence, which is “generally recognized as a reputable source for high-quality practice guidelines.”

Responding to this concern, Dr. Klein said, “There is no specific evidence base for diagnosis. That robust science doesn’t exist. No one has done randomized controlled trials of different methods of diagnosing kids with anxiety. We looked at other position statements, we looked at textbooks, and obviously we drew from our own clinical experience, so it comes from clinical judgment and expert opinion.”

Dr. Henderson also noted that in the future “it will be important to contextualize the recommendations by highlighting the importance of cultural competence in conducting assessments and providing treatment.” Moreover, current evidence can be expanded through the incorporation of diverse cultural and racial perspectives, experiences, and data, she added.

Health service providers should reflect on their own potential biases, which can influence clinician-patient interactions, Dr. Henderson continued. It also is important to consider biases in the evidence, which influence practice. Clinicians should also consider how their recommendations fit with patients’ “cultural and race-based experiences, beliefs, and practices.”

No source of funding for the position statement was reported. Dr. Klein and Dr. Henderson had disclosed no relevant financial relationships.

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

The Canadian Paediatric Society (CPS) has issued a position statement on the diagnosis of anxiety disorders in children and youth. The organization aims to “offer evidence-informed guidance to support pediatric health care providers making decisions around the care of children and adolescents with these conditions.”

“It’s been a long time coming,” lead author Benjamin Klein, MD, assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont., told this news organization. The target audience for the documents includes community pediatricians, subspecialists, family doctors, and nurse practitioners. “There was a great demand from that audience for a position statement, for guidance, obviously in the backdrop of rising child and adolescent mental health incidence over the years and of course COVID,” said Dr. Klein.

The statement was published on the CPS website.
 

‘A comprehensive approach’

Although many other guidelines on this topic are available, it was important to have a Canadian document, said Dr. Klein. “Obviously, there’s going to be a great deal of overlap with European or American guidelines, but it’s just kind of assumed that people want specifically Canadian content. ... Physicians want to know that they’re practicing within a standard of care in Canada.” Dr. Klein is medical director of the Lansdowne Children’s Centre, Brantford, Ont., which provides help for children with communication, developmental, and physical special needs across Ontario.

Anxiety disorders are the most common mental disorders among children and adolescents in Canada, according to the position statement. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) groups these disorders into separation anxiety disorder, selective mutism, specific phobia, social anxiety disorder (social phobia), panic disorder, agoraphobia, and generalized anxiety disorder.

Distinguishing normal, age-appropriate anxiety from anxiety disorder, while also recognizing other comorbidities, is complicated, said Dr. Klein. “Anxiety is one possible diagnosis or feature, and children with mental health and developmental problems often present with a number of problems. Anxiety may be one of them, but if it’s one of them, it may not be the main driver. So, a comprehensive approach is needed ... combining the medical model with biopsychosocial thinking to give a better picture of anxiety in the context of anything else that may be contributing to a presentation.”

The statement outlines recommendations for anxiety assessment, starting with a screening questionnaire such as the Screen for Child Anxiety Related Disorders (SCARED), which is completed by parents and children, to assess symptom severity. Standardized measures for medical, mental health, and developmental histories are available on the CPS website.

The document next recommends an interview about presenting concerns (such as sleep problems or school difficulties), inciting events, and parent-child interactions. The process includes confidential, nonjudgmental interviews with adolescents using a history-taking tool such as HEEADSSS (Home, Education/Employment, Eating, Activities, Drugs, Sexuality, Suicide/Mental Health, and Safety).

“The diagnosis and treatment of anxiety disorders kind of sounds simple if you just read about it as an isolated thing, but the reality is ... there’s no MRI. It’s detective work,” said Dr. Klein. Clinicians must distinguish between normal anxiety, situational anxiety, and specific anxiety disorder, he added. He usually allows 90 minutes for an anxiety assessment, partly to gain the patient’s trust. “These are sensitive issues. It’s common that people don’t trust a diagnosis if you haven’t spent enough time with them. That relational care piece just needs to be there, or people aren’t going to buy in.”

The CPS position statement was reviewed and endorsed by the Canadian Academy of Child and Adolescent Psychiatry.
 

Methodology unclear

Joanna Henderson, MD, professor of psychiatry at the University of Toronto and director of the Margaret and Wallace McCain Centre for Child, Youth, and Family Mental Health at the Centre for Addiction and Mental Health, Toronto, said that the guidelines have been released at an important time. “Conversations about mental health have become more common, and many children, youth, and families are reaching out for support. It is essential that health care professionals be equipped with accessible information about practices to provide appropriate care. These guidelines support that vision.”

It would be helpful to know more about the methods used to arrive at the recommendations, however, said Dr. Henderson. “It is critical that health care providers be guided by evidence-based guidelines that adhere to criteria for establishing high-quality guidelines. Because the authors did not provide information about their methods, I am not able to provide a comment about the quality of their guidelines. There are established approaches for evaluating quality, and I would encourage the authors to publish as a supplement to this article their methods, including in reference to the Appraisal of Guidelines for Research and Evaluation (AGREE II) checklist.”

In the absence of readily available information about methods, she said, “clinicians are encouraged to use guidelines from sources that provide information about the guideline development process and include quality appraisal,” such as the UK National Institute for Health and Care Excellence, which is “generally recognized as a reputable source for high-quality practice guidelines.”

Responding to this concern, Dr. Klein said, “There is no specific evidence base for diagnosis. That robust science doesn’t exist. No one has done randomized controlled trials of different methods of diagnosing kids with anxiety. We looked at other position statements, we looked at textbooks, and obviously we drew from our own clinical experience, so it comes from clinical judgment and expert opinion.”

Dr. Henderson also noted that in the future “it will be important to contextualize the recommendations by highlighting the importance of cultural competence in conducting assessments and providing treatment.” Moreover, current evidence can be expanded through the incorporation of diverse cultural and racial perspectives, experiences, and data, she added.

Health service providers should reflect on their own potential biases, which can influence clinician-patient interactions, Dr. Henderson continued. It also is important to consider biases in the evidence, which influence practice. Clinicians should also consider how their recommendations fit with patients’ “cultural and race-based experiences, beliefs, and practices.”

No source of funding for the position statement was reported. Dr. Klein and Dr. Henderson had disclosed no relevant financial relationships.

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

The Canadian Paediatric Society (CPS) has issued a position statement on the diagnosis of anxiety disorders in children and youth. The organization aims to “offer evidence-informed guidance to support pediatric health care providers making decisions around the care of children and adolescents with these conditions.”

“It’s been a long time coming,” lead author Benjamin Klein, MD, assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont., told this news organization. The target audience for the documents includes community pediatricians, subspecialists, family doctors, and nurse practitioners. “There was a great demand from that audience for a position statement, for guidance, obviously in the backdrop of rising child and adolescent mental health incidence over the years and of course COVID,” said Dr. Klein.

The statement was published on the CPS website.
 

‘A comprehensive approach’

Although many other guidelines on this topic are available, it was important to have a Canadian document, said Dr. Klein. “Obviously, there’s going to be a great deal of overlap with European or American guidelines, but it’s just kind of assumed that people want specifically Canadian content. ... Physicians want to know that they’re practicing within a standard of care in Canada.” Dr. Klein is medical director of the Lansdowne Children’s Centre, Brantford, Ont., which provides help for children with communication, developmental, and physical special needs across Ontario.

Anxiety disorders are the most common mental disorders among children and adolescents in Canada, according to the position statement. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) groups these disorders into separation anxiety disorder, selective mutism, specific phobia, social anxiety disorder (social phobia), panic disorder, agoraphobia, and generalized anxiety disorder.

Distinguishing normal, age-appropriate anxiety from anxiety disorder, while also recognizing other comorbidities, is complicated, said Dr. Klein. “Anxiety is one possible diagnosis or feature, and children with mental health and developmental problems often present with a number of problems. Anxiety may be one of them, but if it’s one of them, it may not be the main driver. So, a comprehensive approach is needed ... combining the medical model with biopsychosocial thinking to give a better picture of anxiety in the context of anything else that may be contributing to a presentation.”

The statement outlines recommendations for anxiety assessment, starting with a screening questionnaire such as the Screen for Child Anxiety Related Disorders (SCARED), which is completed by parents and children, to assess symptom severity. Standardized measures for medical, mental health, and developmental histories are available on the CPS website.

The document next recommends an interview about presenting concerns (such as sleep problems or school difficulties), inciting events, and parent-child interactions. The process includes confidential, nonjudgmental interviews with adolescents using a history-taking tool such as HEEADSSS (Home, Education/Employment, Eating, Activities, Drugs, Sexuality, Suicide/Mental Health, and Safety).

“The diagnosis and treatment of anxiety disorders kind of sounds simple if you just read about it as an isolated thing, but the reality is ... there’s no MRI. It’s detective work,” said Dr. Klein. Clinicians must distinguish between normal anxiety, situational anxiety, and specific anxiety disorder, he added. He usually allows 90 minutes for an anxiety assessment, partly to gain the patient’s trust. “These are sensitive issues. It’s common that people don’t trust a diagnosis if you haven’t spent enough time with them. That relational care piece just needs to be there, or people aren’t going to buy in.”

The CPS position statement was reviewed and endorsed by the Canadian Academy of Child and Adolescent Psychiatry.
 

Methodology unclear

Joanna Henderson, MD, professor of psychiatry at the University of Toronto and director of the Margaret and Wallace McCain Centre for Child, Youth, and Family Mental Health at the Centre for Addiction and Mental Health, Toronto, said that the guidelines have been released at an important time. “Conversations about mental health have become more common, and many children, youth, and families are reaching out for support. It is essential that health care professionals be equipped with accessible information about practices to provide appropriate care. These guidelines support that vision.”

It would be helpful to know more about the methods used to arrive at the recommendations, however, said Dr. Henderson. “It is critical that health care providers be guided by evidence-based guidelines that adhere to criteria for establishing high-quality guidelines. Because the authors did not provide information about their methods, I am not able to provide a comment about the quality of their guidelines. There are established approaches for evaluating quality, and I would encourage the authors to publish as a supplement to this article their methods, including in reference to the Appraisal of Guidelines for Research and Evaluation (AGREE II) checklist.”

In the absence of readily available information about methods, she said, “clinicians are encouraged to use guidelines from sources that provide information about the guideline development process and include quality appraisal,” such as the UK National Institute for Health and Care Excellence, which is “generally recognized as a reputable source for high-quality practice guidelines.”

Responding to this concern, Dr. Klein said, “There is no specific evidence base for diagnosis. That robust science doesn’t exist. No one has done randomized controlled trials of different methods of diagnosing kids with anxiety. We looked at other position statements, we looked at textbooks, and obviously we drew from our own clinical experience, so it comes from clinical judgment and expert opinion.”

Dr. Henderson also noted that in the future “it will be important to contextualize the recommendations by highlighting the importance of cultural competence in conducting assessments and providing treatment.” Moreover, current evidence can be expanded through the incorporation of diverse cultural and racial perspectives, experiences, and data, she added.

Health service providers should reflect on their own potential biases, which can influence clinician-patient interactions, Dr. Henderson continued. It also is important to consider biases in the evidence, which influence practice. Clinicians should also consider how their recommendations fit with patients’ “cultural and race-based experiences, beliefs, and practices.”

No source of funding for the position statement was reported. Dr. Klein and Dr. Henderson had disclosed no relevant financial relationships.

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

Transgender and gender-diverse (TGD) individuals with mental illness appear to have higher rates of posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD) compared with their cisgender counterparts, new research shows.

Although mood disorders, depression, and anxiety were the most common diagnoses in both TGD and cisgender patients, “when we compared the diagnostic profiles [of TGD patients] to those of cisgender patients, we found an increased prevalence of PTSD and BPD,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., told this news organization.

“What we concluded is that psychiatric programs that wish to treat TGD patients should either have or should develop expertise in treating PTSD and BPD, not just mood and anxiety disorders,” Dr. Zimmerman said.

The study was published online September 26 in the Journal of Clinical Psychiatry.
 

‘Piecemeal literature’

TGD individuals “experience high rates of various forms of psychopathology in general and when compared with cisgender persons,” the investigators note.

They point out that most empirical evidence has relied upon the use of brief, unstructured psychodiagnostic assessment measures and assessment of a “limited constellation of psychiatric symptoms domains,” resulting in a “piecemeal literature wherein each piece of research documents elevations in one – or a few – diagnostic domains.”

Studies pointing to broader psychosocial health variables have often relied upon self-reported measures. In addition, in studies that utilized a structured interview approach, none “used a formal interview procedure to assess psychiatric diagnoses” and most focused only on a “limited number of psychiatric conditions based on self-reports of past diagnosis.”

The goal of the current study was to use semistructured interviews administered by professionals to compare the diagnostic profiles of a samples of TGD and cisgender patients who presented for treatment at a single naturalistic, clinically acute setting – a partial hospital program.

Dr. Zimmerman said that there was an additional motive for conducting the study. “There has been discussion in the field as to whether or not transgender or gender-diverse individuals all have borderline personality disorder, but that hasn’t been our clinical impression.”

Rather, Dr. Zimmerman and colleagues believe TGD people “may have had more difficult childhoods and more difficult adjustments in society because of societal attitudes and have to deal with that stress, whether it be microaggressions or overt bullying and aggression.” The study was designed to investigate this issue.

In addition, studies conducted in primary care programs in individuals seeking gender-affirming surgery have “reported a limited number of psychiatric diagnoses, but we were wondering whether, amongst psychiatric patients specifically, there were differences in diagnostic profiles between transgender and gender-diverse patients and cisgender patients. If so, what might the implications be for providing care for this population?”
 

TGD not synonymous with borderline

To investigate, the researchers administered semistructured diagnostic interviews for DSM-IV disorders to 2,212 psychiatric patients (66% cisgender women, 30.8% cisgender men, 3.1% TGD; mean [standard deviation] age 36.7 [14.4] years) presenting to the Rhode Island Hospital Department of Psychiatry Partial Hospital Program between April 2014 and January 2021.

Patients also completed a demographic questionnaire including their assigned sex at birth and their current gender identity.

Most patients (44.9%) were single, followed by 23.5% who were married, 14.1% living in a relationship as if married, 12.0% divorced, 3.6% separated, and 1.9% widowed.

Almost three-quarters of participants (73.2%) identified as White, followed by Hispanic (10.7%), Black (6.7%), “other” or a combination of racial/ethnic backgrounds (6.6%), and Asian (2.7%).

There were no differences between cisgender and TGD groups in terms of race or education, but the TGD patients were significantly younger compared with their cisgender counterparts and were significantly more likely to have never been married.

The average number of psychiatric diagnoses in the sample was 3.05 (± 1.73), with TGD patients having a larger number of psychiatric diagnoses than did their cisgender peers (an average of 3.54 ± 1.88 vs. 3.04 ± 1.72, respectively; t = 2.37; P = .02).

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were the most common disorders among both cisgender and TGD patients. However, after controlling for age, the researchers found that TGD patients were significantly more likely than were the cisgender patients to be diagnosed with PTSD and BPD (P < .05 for both).

A representative sample?

Commenting on the study, Jack Drescher, MD, distinguished life fellow of the American Psychiatric Association and clinical professor of psychiatry, Columbia University, New York, called the findings “interesting” but noted that a limitation of the study is that it included “a patient population with likely more severe psychiatric illness, since they were all day hospital patients.”

The question is whether similar findings would be obtained in a less severely ill population, said Dr. Drescher, who is also a senior consulting analyst for sexuality and gender at Columbia University and was not involved with the study. “The patients in the study may not be representative of the general population, either cisgender or transgender.”

Dr. Drescher was “not surprised” by the finding regarding PTSD because the finding “is consistent with our understanding of the kinds of traumas that transgender people go through in day-to-day life.”

He noted that some people misunderstand the diagnostic criterion in BPD of identity confusion and think that because people with gender dysphoria may be confused about their identity, it means that all people who are transgender have borderline personality disorder, “but that’s not true.”

Dr. Zimmerman agreed. “The vast majority of individuals with BPD do not have a transgender or gender-diverse identity, and TGD should not be equated with BPD,” he said.

No source of study funding was disclosed. Dr. Zimmerman and coauthors and Dr. Drescher report no relevant financial relationships.

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

Transgender and gender-diverse (TGD) individuals with mental illness appear to have higher rates of posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD) compared with their cisgender counterparts, new research shows.

Although mood disorders, depression, and anxiety were the most common diagnoses in both TGD and cisgender patients, “when we compared the diagnostic profiles [of TGD patients] to those of cisgender patients, we found an increased prevalence of PTSD and BPD,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., told this news organization.

“What we concluded is that psychiatric programs that wish to treat TGD patients should either have or should develop expertise in treating PTSD and BPD, not just mood and anxiety disorders,” Dr. Zimmerman said.

The study was published online September 26 in the Journal of Clinical Psychiatry.
 

‘Piecemeal literature’

TGD individuals “experience high rates of various forms of psychopathology in general and when compared with cisgender persons,” the investigators note.

They point out that most empirical evidence has relied upon the use of brief, unstructured psychodiagnostic assessment measures and assessment of a “limited constellation of psychiatric symptoms domains,” resulting in a “piecemeal literature wherein each piece of research documents elevations in one – or a few – diagnostic domains.”

Studies pointing to broader psychosocial health variables have often relied upon self-reported measures. In addition, in studies that utilized a structured interview approach, none “used a formal interview procedure to assess psychiatric diagnoses” and most focused only on a “limited number of psychiatric conditions based on self-reports of past diagnosis.”

The goal of the current study was to use semistructured interviews administered by professionals to compare the diagnostic profiles of a samples of TGD and cisgender patients who presented for treatment at a single naturalistic, clinically acute setting – a partial hospital program.

Dr. Zimmerman said that there was an additional motive for conducting the study. “There has been discussion in the field as to whether or not transgender or gender-diverse individuals all have borderline personality disorder, but that hasn’t been our clinical impression.”

Rather, Dr. Zimmerman and colleagues believe TGD people “may have had more difficult childhoods and more difficult adjustments in society because of societal attitudes and have to deal with that stress, whether it be microaggressions or overt bullying and aggression.” The study was designed to investigate this issue.

In addition, studies conducted in primary care programs in individuals seeking gender-affirming surgery have “reported a limited number of psychiatric diagnoses, but we were wondering whether, amongst psychiatric patients specifically, there were differences in diagnostic profiles between transgender and gender-diverse patients and cisgender patients. If so, what might the implications be for providing care for this population?”
 

TGD not synonymous with borderline

To investigate, the researchers administered semistructured diagnostic interviews for DSM-IV disorders to 2,212 psychiatric patients (66% cisgender women, 30.8% cisgender men, 3.1% TGD; mean [standard deviation] age 36.7 [14.4] years) presenting to the Rhode Island Hospital Department of Psychiatry Partial Hospital Program between April 2014 and January 2021.

Patients also completed a demographic questionnaire including their assigned sex at birth and their current gender identity.

Most patients (44.9%) were single, followed by 23.5% who were married, 14.1% living in a relationship as if married, 12.0% divorced, 3.6% separated, and 1.9% widowed.

Almost three-quarters of participants (73.2%) identified as White, followed by Hispanic (10.7%), Black (6.7%), “other” or a combination of racial/ethnic backgrounds (6.6%), and Asian (2.7%).

There were no differences between cisgender and TGD groups in terms of race or education, but the TGD patients were significantly younger compared with their cisgender counterparts and were significantly more likely to have never been married.

The average number of psychiatric diagnoses in the sample was 3.05 (± 1.73), with TGD patients having a larger number of psychiatric diagnoses than did their cisgender peers (an average of 3.54 ± 1.88 vs. 3.04 ± 1.72, respectively; t = 2.37; P = .02).

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were the most common disorders among both cisgender and TGD patients. However, after controlling for age, the researchers found that TGD patients were significantly more likely than were the cisgender patients to be diagnosed with PTSD and BPD (P < .05 for both).

A representative sample?

Commenting on the study, Jack Drescher, MD, distinguished life fellow of the American Psychiatric Association and clinical professor of psychiatry, Columbia University, New York, called the findings “interesting” but noted that a limitation of the study is that it included “a patient population with likely more severe psychiatric illness, since they were all day hospital patients.”

The question is whether similar findings would be obtained in a less severely ill population, said Dr. Drescher, who is also a senior consulting analyst for sexuality and gender at Columbia University and was not involved with the study. “The patients in the study may not be representative of the general population, either cisgender or transgender.”

Dr. Drescher was “not surprised” by the finding regarding PTSD because the finding “is consistent with our understanding of the kinds of traumas that transgender people go through in day-to-day life.”

He noted that some people misunderstand the diagnostic criterion in BPD of identity confusion and think that because people with gender dysphoria may be confused about their identity, it means that all people who are transgender have borderline personality disorder, “but that’s not true.”

Dr. Zimmerman agreed. “The vast majority of individuals with BPD do not have a transgender or gender-diverse identity, and TGD should not be equated with BPD,” he said.

No source of study funding was disclosed. Dr. Zimmerman and coauthors and Dr. Drescher report no relevant financial relationships.

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

Transgender and gender-diverse (TGD) individuals with mental illness appear to have higher rates of posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD) compared with their cisgender counterparts, new research shows.

Although mood disorders, depression, and anxiety were the most common diagnoses in both TGD and cisgender patients, “when we compared the diagnostic profiles [of TGD patients] to those of cisgender patients, we found an increased prevalence of PTSD and BPD,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., told this news organization.

“What we concluded is that psychiatric programs that wish to treat TGD patients should either have or should develop expertise in treating PTSD and BPD, not just mood and anxiety disorders,” Dr. Zimmerman said.

The study was published online September 26 in the Journal of Clinical Psychiatry.
 

‘Piecemeal literature’

TGD individuals “experience high rates of various forms of psychopathology in general and when compared with cisgender persons,” the investigators note.

They point out that most empirical evidence has relied upon the use of brief, unstructured psychodiagnostic assessment measures and assessment of a “limited constellation of psychiatric symptoms domains,” resulting in a “piecemeal literature wherein each piece of research documents elevations in one – or a few – diagnostic domains.”

Studies pointing to broader psychosocial health variables have often relied upon self-reported measures. In addition, in studies that utilized a structured interview approach, none “used a formal interview procedure to assess psychiatric diagnoses” and most focused only on a “limited number of psychiatric conditions based on self-reports of past diagnosis.”

The goal of the current study was to use semistructured interviews administered by professionals to compare the diagnostic profiles of a samples of TGD and cisgender patients who presented for treatment at a single naturalistic, clinically acute setting – a partial hospital program.

Dr. Zimmerman said that there was an additional motive for conducting the study. “There has been discussion in the field as to whether or not transgender or gender-diverse individuals all have borderline personality disorder, but that hasn’t been our clinical impression.”

Rather, Dr. Zimmerman and colleagues believe TGD people “may have had more difficult childhoods and more difficult adjustments in society because of societal attitudes and have to deal with that stress, whether it be microaggressions or overt bullying and aggression.” The study was designed to investigate this issue.

In addition, studies conducted in primary care programs in individuals seeking gender-affirming surgery have “reported a limited number of psychiatric diagnoses, but we were wondering whether, amongst psychiatric patients specifically, there were differences in diagnostic profiles between transgender and gender-diverse patients and cisgender patients. If so, what might the implications be for providing care for this population?”
 

TGD not synonymous with borderline

To investigate, the researchers administered semistructured diagnostic interviews for DSM-IV disorders to 2,212 psychiatric patients (66% cisgender women, 30.8% cisgender men, 3.1% TGD; mean [standard deviation] age 36.7 [14.4] years) presenting to the Rhode Island Hospital Department of Psychiatry Partial Hospital Program between April 2014 and January 2021.

Patients also completed a demographic questionnaire including their assigned sex at birth and their current gender identity.

Most patients (44.9%) were single, followed by 23.5% who were married, 14.1% living in a relationship as if married, 12.0% divorced, 3.6% separated, and 1.9% widowed.

Almost three-quarters of participants (73.2%) identified as White, followed by Hispanic (10.7%), Black (6.7%), “other” or a combination of racial/ethnic backgrounds (6.6%), and Asian (2.7%).

There were no differences between cisgender and TGD groups in terms of race or education, but the TGD patients were significantly younger compared with their cisgender counterparts and were significantly more likely to have never been married.

The average number of psychiatric diagnoses in the sample was 3.05 (± 1.73), with TGD patients having a larger number of psychiatric diagnoses than did their cisgender peers (an average of 3.54 ± 1.88 vs. 3.04 ± 1.72, respectively; t = 2.37; P = .02).

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were the most common disorders among both cisgender and TGD patients. However, after controlling for age, the researchers found that TGD patients were significantly more likely than were the cisgender patients to be diagnosed with PTSD and BPD (P < .05 for both).

A representative sample?

Commenting on the study, Jack Drescher, MD, distinguished life fellow of the American Psychiatric Association and clinical professor of psychiatry, Columbia University, New York, called the findings “interesting” but noted that a limitation of the study is that it included “a patient population with likely more severe psychiatric illness, since they were all day hospital patients.”

The question is whether similar findings would be obtained in a less severely ill population, said Dr. Drescher, who is also a senior consulting analyst for sexuality and gender at Columbia University and was not involved with the study. “The patients in the study may not be representative of the general population, either cisgender or transgender.”

Dr. Drescher was “not surprised” by the finding regarding PTSD because the finding “is consistent with our understanding of the kinds of traumas that transgender people go through in day-to-day life.”

He noted that some people misunderstand the diagnostic criterion in BPD of identity confusion and think that because people with gender dysphoria may be confused about their identity, it means that all people who are transgender have borderline personality disorder, “but that’s not true.”

Dr. Zimmerman agreed. “The vast majority of individuals with BPD do not have a transgender or gender-diverse identity, and TGD should not be equated with BPD,” he said.

No source of study funding was disclosed. Dr. Zimmerman and coauthors and Dr. Drescher report no relevant financial relationships.

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

An analysis of more than 800,000 women in Denmark offers more insight into the murky links between female hormones and midlife mental illness in women: It hints that hormone therapy (HT) may boost the risk of depression, have no effect, or lower it – all depending on how it’s administered and when.

Women who took systemic HT had a higher risk of depression from age 48 to 50 (adjusted hazard ratio, 1.50; 95% confidence interval, 1.24-1.81), researchers reported in JAMA Network Open. However, there was no overall link between depression and locally administered HT (aHR, 1.15; 95% CI, 0.70-1.87) – except when HT was begun between ages 54 and 60, when there were signs of a protective effect (aHR, 0.80; 95% CI, 0.70-0.91).

“Women in menopause who initiate systemically administered HT should be aware of depression as a potential adverse effect,” epidemiologist and study corresponding author Merete Osler, MD, PhD, DMSc, of Bispebjerg and Frederiksberg (Denmark) Hospitals and the University of Copenhagen, said in an interview. ”Further, women and clinicians alike should be aware of any misinterpretation of symptoms of depression as menopausal disturbances.”

Dr. Osler said the researchers launched the study to better understand potential hormone-depression links in light of suspicions that lower levels of estrogen in menopause may contribute to depression.

Several randomized clinical trials and cohort and cross-sectional studies have explored whether systemic HT affects depression during menopause, Dr. Osler said, “but the results from these studies have been inconsistent, and few have explored the role of the route of administration.”

For the new registry-based study, researchers retrospectively tracked all women in Denmark who were aged 45 between 1995 and 2017 without prior oophorectomy, certain kinds of cancer, prior use of HT, or ongoing depression.

During follow-up to a mean age of 56, 23% of the women began HT (at a median age of 55), and 1.6% were hospitalized for depression. Of those on HT, 65.8% received locally administered HT.

Researchers adjusted hazard ratios for a long list of factors such as educational level, marital status, number of still births or live births, prior use of hormonal contraceptives, several medical conditions, and prior depression.

“We were surprised by our findings, which to some degree contradicted our prior hypothesis that systemic HT with estrogen would not be associated with first-time depression diagnosis in women aged 45 and above, while HT with progesterone would be associated with a slightly increased risk,” Dr. Osler said. “In our study, systemically administered HT was associated with an increased risk of depression with no difference between estrogen alone or in combination with progestin. As findings from previous studies have been inconsistent, our findings fit with some but not all previous studies.”

Why might the mode of administration make a difference? It’s possible that local administration may contribute less to the systemic circulation, Dr. Osler said, “or that menopausal symptoms including depression are more likely to be treated with systemic HT.”

As for age differences, Dr. Osler said “it is possible that women are more sensitive to the influence of HT on mood around menopause than at later ages. However, it should be noted that in the present study it was not possible to calculate precise risk estimates for use of systemic HT in menopausal women above age 54 because less than 1% initiated treatment with systemic HT after age 54 years.”

In an interview, psychiatrist Natalie Rasgon, MD, PhD, of Stanford (Calif.) University, who’s studied hormones and depression, said the study is “remarkably large and consistently executed.”

She cautioned, however, that the findings don’t prove any causality. “Saying that estrogen therapy or hormone therapy causes depression is patently incorrect.”

How can the findings be useful for medical professionals? “Women and physicians alike need to be very mindful of pre-existing mood disorders,” Dr. Rasgon said. “Women who in the past had anxiety disorders, mood swings, PTSD, or prior episodes of depression might have a differential response to hormone therapy in menopause.”

Also keep in mind, she said, that the transition from menopause to post menopause is “very volatile,” and depression may break through even in women undergoing treatment for the condition.

For her part, Dr. Osler said this study and others “emphasize the need for clinical guidelines to further consider the psychological side effects of systemic HT.”

Funding information was not provided. The study authors and Dr. Rasgon have no disclosures.

An analysis of more than 800,000 women in Denmark offers more insight into the murky links between female hormones and midlife mental illness in women: It hints that hormone therapy (HT) may boost the risk of depression, have no effect, or lower it – all depending on how it’s administered and when.

Women who took systemic HT had a higher risk of depression from age 48 to 50 (adjusted hazard ratio, 1.50; 95% confidence interval, 1.24-1.81), researchers reported in JAMA Network Open. However, there was no overall link between depression and locally administered HT (aHR, 1.15; 95% CI, 0.70-1.87) – except when HT was begun between ages 54 and 60, when there were signs of a protective effect (aHR, 0.80; 95% CI, 0.70-0.91).

“Women in menopause who initiate systemically administered HT should be aware of depression as a potential adverse effect,” epidemiologist and study corresponding author Merete Osler, MD, PhD, DMSc, of Bispebjerg and Frederiksberg (Denmark) Hospitals and the University of Copenhagen, said in an interview. ”Further, women and clinicians alike should be aware of any misinterpretation of symptoms of depression as menopausal disturbances.”

Dr. Osler said the researchers launched the study to better understand potential hormone-depression links in light of suspicions that lower levels of estrogen in menopause may contribute to depression.

Several randomized clinical trials and cohort and cross-sectional studies have explored whether systemic HT affects depression during menopause, Dr. Osler said, “but the results from these studies have been inconsistent, and few have explored the role of the route of administration.”

For the new registry-based study, researchers retrospectively tracked all women in Denmark who were aged 45 between 1995 and 2017 without prior oophorectomy, certain kinds of cancer, prior use of HT, or ongoing depression.

During follow-up to a mean age of 56, 23% of the women began HT (at a median age of 55), and 1.6% were hospitalized for depression. Of those on HT, 65.8% received locally administered HT.

Researchers adjusted hazard ratios for a long list of factors such as educational level, marital status, number of still births or live births, prior use of hormonal contraceptives, several medical conditions, and prior depression.

“We were surprised by our findings, which to some degree contradicted our prior hypothesis that systemic HT with estrogen would not be associated with first-time depression diagnosis in women aged 45 and above, while HT with progesterone would be associated with a slightly increased risk,” Dr. Osler said. “In our study, systemically administered HT was associated with an increased risk of depression with no difference between estrogen alone or in combination with progestin. As findings from previous studies have been inconsistent, our findings fit with some but not all previous studies.”

Why might the mode of administration make a difference? It’s possible that local administration may contribute less to the systemic circulation, Dr. Osler said, “or that menopausal symptoms including depression are more likely to be treated with systemic HT.”

As for age differences, Dr. Osler said “it is possible that women are more sensitive to the influence of HT on mood around menopause than at later ages. However, it should be noted that in the present study it was not possible to calculate precise risk estimates for use of systemic HT in menopausal women above age 54 because less than 1% initiated treatment with systemic HT after age 54 years.”

In an interview, psychiatrist Natalie Rasgon, MD, PhD, of Stanford (Calif.) University, who’s studied hormones and depression, said the study is “remarkably large and consistently executed.”

She cautioned, however, that the findings don’t prove any causality. “Saying that estrogen therapy or hormone therapy causes depression is patently incorrect.”

How can the findings be useful for medical professionals? “Women and physicians alike need to be very mindful of pre-existing mood disorders,” Dr. Rasgon said. “Women who in the past had anxiety disorders, mood swings, PTSD, or prior episodes of depression might have a differential response to hormone therapy in menopause.”

Also keep in mind, she said, that the transition from menopause to post menopause is “very volatile,” and depression may break through even in women undergoing treatment for the condition.

For her part, Dr. Osler said this study and others “emphasize the need for clinical guidelines to further consider the psychological side effects of systemic HT.”

Funding information was not provided. The study authors and Dr. Rasgon have no disclosures.

An analysis of more than 800,000 women in Denmark offers more insight into the murky links between female hormones and midlife mental illness in women: It hints that hormone therapy (HT) may boost the risk of depression, have no effect, or lower it – all depending on how it’s administered and when.

Women who took systemic HT had a higher risk of depression from age 48 to 50 (adjusted hazard ratio, 1.50; 95% confidence interval, 1.24-1.81), researchers reported in JAMA Network Open. However, there was no overall link between depression and locally administered HT (aHR, 1.15; 95% CI, 0.70-1.87) – except when HT was begun between ages 54 and 60, when there were signs of a protective effect (aHR, 0.80; 95% CI, 0.70-0.91).

“Women in menopause who initiate systemically administered HT should be aware of depression as a potential adverse effect,” epidemiologist and study corresponding author Merete Osler, MD, PhD, DMSc, of Bispebjerg and Frederiksberg (Denmark) Hospitals and the University of Copenhagen, said in an interview. ”Further, women and clinicians alike should be aware of any misinterpretation of symptoms of depression as menopausal disturbances.”

Dr. Osler said the researchers launched the study to better understand potential hormone-depression links in light of suspicions that lower levels of estrogen in menopause may contribute to depression.

Several randomized clinical trials and cohort and cross-sectional studies have explored whether systemic HT affects depression during menopause, Dr. Osler said, “but the results from these studies have been inconsistent, and few have explored the role of the route of administration.”

For the new registry-based study, researchers retrospectively tracked all women in Denmark who were aged 45 between 1995 and 2017 without prior oophorectomy, certain kinds of cancer, prior use of HT, or ongoing depression.

During follow-up to a mean age of 56, 23% of the women began HT (at a median age of 55), and 1.6% were hospitalized for depression. Of those on HT, 65.8% received locally administered HT.

Researchers adjusted hazard ratios for a long list of factors such as educational level, marital status, number of still births or live births, prior use of hormonal contraceptives, several medical conditions, and prior depression.

“We were surprised by our findings, which to some degree contradicted our prior hypothesis that systemic HT with estrogen would not be associated with first-time depression diagnosis in women aged 45 and above, while HT with progesterone would be associated with a slightly increased risk,” Dr. Osler said. “In our study, systemically administered HT was associated with an increased risk of depression with no difference between estrogen alone or in combination with progestin. As findings from previous studies have been inconsistent, our findings fit with some but not all previous studies.”

Why might the mode of administration make a difference? It’s possible that local administration may contribute less to the systemic circulation, Dr. Osler said, “or that menopausal symptoms including depression are more likely to be treated with systemic HT.”

As for age differences, Dr. Osler said “it is possible that women are more sensitive to the influence of HT on mood around menopause than at later ages. However, it should be noted that in the present study it was not possible to calculate precise risk estimates for use of systemic HT in menopausal women above age 54 because less than 1% initiated treatment with systemic HT after age 54 years.”

In an interview, psychiatrist Natalie Rasgon, MD, PhD, of Stanford (Calif.) University, who’s studied hormones and depression, said the study is “remarkably large and consistently executed.”

She cautioned, however, that the findings don’t prove any causality. “Saying that estrogen therapy or hormone therapy causes depression is patently incorrect.”

How can the findings be useful for medical professionals? “Women and physicians alike need to be very mindful of pre-existing mood disorders,” Dr. Rasgon said. “Women who in the past had anxiety disorders, mood swings, PTSD, or prior episodes of depression might have a differential response to hormone therapy in menopause.”

Also keep in mind, she said, that the transition from menopause to post menopause is “very volatile,” and depression may break through even in women undergoing treatment for the condition.

For her part, Dr. Osler said this study and others “emphasize the need for clinical guidelines to further consider the psychological side effects of systemic HT.”

Funding information was not provided. The study authors and Dr. Rasgon have no disclosures.

Visits to emergency departments following sexual assault increased 15-fold from 2006 through 2019, as determined from a national database of visits to hospitals in the United States.

Data from the Federal Bureau of Investigation show an increase in reported rapes and sexual assaults (SAs) since 2006, and studies of victims show an increased risk of conditions such as suicidal ideation, PTSD, depression, substance use, and chronic conditions, write Emily L. Vogt of the University of Michigan, Ann Arbor, and colleagues.

However, trends and disparities in ED use by adults seeking care following SA have not been explored, they said.

For a study that was published in JAMA Network Open, researchers reviewed data from the Nationwide Emergency Department Sample (NEDS), a large, nationally representative database managed by the Agency for Healthcare Research and Quality. The dataset consisted of 120 million to 143 million weighted ED visits reported annually from 2006 through 2016. The study population included adults aged 18-65 years who had made an ED visit that was recorded in the NEDS and that was coded as an SA. SA was defined using ICD-9 codes until the fourth quarter of 2015, at which time ICD-10 codes came into use.

Overall, the number of SA-related ED visits increased by 1,533.0% during the study period, from 3,607 in 2006 to 55,296 in 2019. The average annual percentage change was 23.0% (P < .001). The greatest increase occurred from 2015 to 2016, when annual visits increased from 17,709 to 47,732. This increase likely reflected the updated ICD-10 codes, in which there are categories for suspected adult rape, confirmed adult rape, and adult forced sexual exploitation, the researchers note.

Patients presenting to the ED after an SA were mainly women (91.5%). Individuals aged 18-25 years accounted for nearly half of the presentations. Individuals in the lowest and second-lowest income quartiles also were overrepresented.

Despite the increased presentation to EDs, admission rates for SA decreased, from 12.6% to 4.3%, the researchers note. Patients who were older and were insured through Medicaid were more likely to be admitted than persons of other demographic groups.

The researchers also found that increases in ED presentations outpaced increases in SA reports to law enforcement. They compared the ED trends with FBI-reported rapes/SAs from 2015 to 2019 and found increases of 7% and 22% during the times of ICD-9 and ICD-10 codes, respectively. However, in 2019, the number of SA survivors who sought ED care remained below the number who reported to law enforcement (55,296 vs. 139,815, as determined on the basis of revised SA definitions).

“Although the association between increased coding specificity and documentation of SA is still unclear, ICD-10 likely contributed to increased ED documentation of SA,” but the data show steady increases that are independent of the coding change, the researchers write.

The study findings were limited by several factors, including the potential for multiple representations of patients, coding errors associated with the NEDS database, and the reliance on voluntary reports in the NEDS and FBI datasets, the researchers note. The results were strengthened by the large, diverse sample size and by the inclusion of hospital admissions and crime data for comparison, they say.

“As few as 21% of survivors seek medical care after SA, meaning that the survivors captured in this study represent a fraction of total SA-related care need,” the researchers write. “Our finding that most SA ED visits are by young, female, and low-income survivors can inform policy changes to better support these individuals,” which could include the development of outpatient and longitudinal care settings to better serve these populations, they conclude.

Better understanding not only of the trends underlying SA reporting but also of the demographics of survivors who seek treatment and evaluation after SA is vital, said Robert Glatter, MD, in an interview.

“Being able to better understand how social and societal movements affect a patient’s comfort in reporting an SA is vital in tracking the numbers of people who seek care in the ED,” said Dr. Glatter, an emergency medicine physician at Lenox Hill Hospital at Northwell Health, New York, and also of Hofstra University, Hempstead, N.Y.

Dr. Glatter said he was not surprised by the significant increase in sexual assault presentations, especially in light of increased awareness and the influence of the #MeToo movement and other social justice movements over the past decade.

“While I believe that victims of sexual violence may now feel more empowered to report an assault, the volume of SA that go unreported remains a serious public health issue and concern” in the United States and globally, he emphasized.

A key message from the current study is that there is a need for investment in “compassionate and comprehensive care for all survivors of SA,” Dr. Glatter said. “This includes recognition of the extensive mental health consequences of SA that can lead to not only depression, PTSD, and anxiety but also to suicidal ideation and suicide. The longer-term medical effects become life altering, permeating families and future generations,” he emphasized.

“As a society, we must also place a strong emphasis on caring for all SA survivors, but particularly those who come from economically or socially disadvantaged backgrounds who are uninsured or underinsured,” Dr. Glatter said. Issues of race, gender identity, and sexual identity among SA survivors also must be taken into consideration, he added.

“We need to better understand how our health care system can provide more nuanced follow-up care and reporting for survivors in outpatient settings. … Making access easier, while ensuring confidentiality, will allow more survivors of SA to seek treatment and care,” he said. “We also need to understand how using forensic nurses in this capacity, and beyond the ED, can better serve minority and racially diverse communities” and to increase the recruitment and training of such specialized nurses to care for SA victims, Dr. Glatter noted.

The study was supported by internal funding from the University of Michigan and the department of obstetrics and gynecology. Corresponding author Erica C. Marsh, MD, has received personal fees from Myovant Sciences and Pfizer unrelated to the current study. Dr. Glatter has disclosed no relevant financial relationships.

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

Visits to emergency departments following sexual assault increased 15-fold from 2006 through 2019, as determined from a national database of visits to hospitals in the United States.

Data from the Federal Bureau of Investigation show an increase in reported rapes and sexual assaults (SAs) since 2006, and studies of victims show an increased risk of conditions such as suicidal ideation, PTSD, depression, substance use, and chronic conditions, write Emily L. Vogt of the University of Michigan, Ann Arbor, and colleagues.

However, trends and disparities in ED use by adults seeking care following SA have not been explored, they said.

For a study that was published in JAMA Network Open, researchers reviewed data from the Nationwide Emergency Department Sample (NEDS), a large, nationally representative database managed by the Agency for Healthcare Research and Quality. The dataset consisted of 120 million to 143 million weighted ED visits reported annually from 2006 through 2016. The study population included adults aged 18-65 years who had made an ED visit that was recorded in the NEDS and that was coded as an SA. SA was defined using ICD-9 codes until the fourth quarter of 2015, at which time ICD-10 codes came into use.

Overall, the number of SA-related ED visits increased by 1,533.0% during the study period, from 3,607 in 2006 to 55,296 in 2019. The average annual percentage change was 23.0% (P < .001). The greatest increase occurred from 2015 to 2016, when annual visits increased from 17,709 to 47,732. This increase likely reflected the updated ICD-10 codes, in which there are categories for suspected adult rape, confirmed adult rape, and adult forced sexual exploitation, the researchers note.

Patients presenting to the ED after an SA were mainly women (91.5%). Individuals aged 18-25 years accounted for nearly half of the presentations. Individuals in the lowest and second-lowest income quartiles also were overrepresented.

Despite the increased presentation to EDs, admission rates for SA decreased, from 12.6% to 4.3%, the researchers note. Patients who were older and were insured through Medicaid were more likely to be admitted than persons of other demographic groups.

The researchers also found that increases in ED presentations outpaced increases in SA reports to law enforcement. They compared the ED trends with FBI-reported rapes/SAs from 2015 to 2019 and found increases of 7% and 22% during the times of ICD-9 and ICD-10 codes, respectively. However, in 2019, the number of SA survivors who sought ED care remained below the number who reported to law enforcement (55,296 vs. 139,815, as determined on the basis of revised SA definitions).

“Although the association between increased coding specificity and documentation of SA is still unclear, ICD-10 likely contributed to increased ED documentation of SA,” but the data show steady increases that are independent of the coding change, the researchers write.

The study findings were limited by several factors, including the potential for multiple representations of patients, coding errors associated with the NEDS database, and the reliance on voluntary reports in the NEDS and FBI datasets, the researchers note. The results were strengthened by the large, diverse sample size and by the inclusion of hospital admissions and crime data for comparison, they say.

“As few as 21% of survivors seek medical care after SA, meaning that the survivors captured in this study represent a fraction of total SA-related care need,” the researchers write. “Our finding that most SA ED visits are by young, female, and low-income survivors can inform policy changes to better support these individuals,” which could include the development of outpatient and longitudinal care settings to better serve these populations, they conclude.

Better understanding not only of the trends underlying SA reporting but also of the demographics of survivors who seek treatment and evaluation after SA is vital, said Robert Glatter, MD, in an interview.

“Being able to better understand how social and societal movements affect a patient’s comfort in reporting an SA is vital in tracking the numbers of people who seek care in the ED,” said Dr. Glatter, an emergency medicine physician at Lenox Hill Hospital at Northwell Health, New York, and also of Hofstra University, Hempstead, N.Y.

Dr. Glatter said he was not surprised by the significant increase in sexual assault presentations, especially in light of increased awareness and the influence of the #MeToo movement and other social justice movements over the past decade.

“While I believe that victims of sexual violence may now feel more empowered to report an assault, the volume of SA that go unreported remains a serious public health issue and concern” in the United States and globally, he emphasized.

A key message from the current study is that there is a need for investment in “compassionate and comprehensive care for all survivors of SA,” Dr. Glatter said. “This includes recognition of the extensive mental health consequences of SA that can lead to not only depression, PTSD, and anxiety but also to suicidal ideation and suicide. The longer-term medical effects become life altering, permeating families and future generations,” he emphasized.

“As a society, we must also place a strong emphasis on caring for all SA survivors, but particularly those who come from economically or socially disadvantaged backgrounds who are uninsured or underinsured,” Dr. Glatter said. Issues of race, gender identity, and sexual identity among SA survivors also must be taken into consideration, he added.

“We need to better understand how our health care system can provide more nuanced follow-up care and reporting for survivors in outpatient settings. … Making access easier, while ensuring confidentiality, will allow more survivors of SA to seek treatment and care,” he said. “We also need to understand how using forensic nurses in this capacity, and beyond the ED, can better serve minority and racially diverse communities” and to increase the recruitment and training of such specialized nurses to care for SA victims, Dr. Glatter noted.

The study was supported by internal funding from the University of Michigan and the department of obstetrics and gynecology. Corresponding author Erica C. Marsh, MD, has received personal fees from Myovant Sciences and Pfizer unrelated to the current study. Dr. Glatter has disclosed no relevant financial relationships.

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

Visits to emergency departments following sexual assault increased 15-fold from 2006 through 2019, as determined from a national database of visits to hospitals in the United States.

Data from the Federal Bureau of Investigation show an increase in reported rapes and sexual assaults (SAs) since 2006, and studies of victims show an increased risk of conditions such as suicidal ideation, PTSD, depression, substance use, and chronic conditions, write Emily L. Vogt of the University of Michigan, Ann Arbor, and colleagues.

However, trends and disparities in ED use by adults seeking care following SA have not been explored, they said.

For a study that was published in JAMA Network Open, researchers reviewed data from the Nationwide Emergency Department Sample (NEDS), a large, nationally representative database managed by the Agency for Healthcare Research and Quality. The dataset consisted of 120 million to 143 million weighted ED visits reported annually from 2006 through 2016. The study population included adults aged 18-65 years who had made an ED visit that was recorded in the NEDS and that was coded as an SA. SA was defined using ICD-9 codes until the fourth quarter of 2015, at which time ICD-10 codes came into use.

Overall, the number of SA-related ED visits increased by 1,533.0% during the study period, from 3,607 in 2006 to 55,296 in 2019. The average annual percentage change was 23.0% (P < .001). The greatest increase occurred from 2015 to 2016, when annual visits increased from 17,709 to 47,732. This increase likely reflected the updated ICD-10 codes, in which there are categories for suspected adult rape, confirmed adult rape, and adult forced sexual exploitation, the researchers note.

Patients presenting to the ED after an SA were mainly women (91.5%). Individuals aged 18-25 years accounted for nearly half of the presentations. Individuals in the lowest and second-lowest income quartiles also were overrepresented.

Despite the increased presentation to EDs, admission rates for SA decreased, from 12.6% to 4.3%, the researchers note. Patients who were older and were insured through Medicaid were more likely to be admitted than persons of other demographic groups.

The researchers also found that increases in ED presentations outpaced increases in SA reports to law enforcement. They compared the ED trends with FBI-reported rapes/SAs from 2015 to 2019 and found increases of 7% and 22% during the times of ICD-9 and ICD-10 codes, respectively. However, in 2019, the number of SA survivors who sought ED care remained below the number who reported to law enforcement (55,296 vs. 139,815, as determined on the basis of revised SA definitions).

“Although the association between increased coding specificity and documentation of SA is still unclear, ICD-10 likely contributed to increased ED documentation of SA,” but the data show steady increases that are independent of the coding change, the researchers write.

The study findings were limited by several factors, including the potential for multiple representations of patients, coding errors associated with the NEDS database, and the reliance on voluntary reports in the NEDS and FBI datasets, the researchers note. The results were strengthened by the large, diverse sample size and by the inclusion of hospital admissions and crime data for comparison, they say.

“As few as 21% of survivors seek medical care after SA, meaning that the survivors captured in this study represent a fraction of total SA-related care need,” the researchers write. “Our finding that most SA ED visits are by young, female, and low-income survivors can inform policy changes to better support these individuals,” which could include the development of outpatient and longitudinal care settings to better serve these populations, they conclude.

Better understanding not only of the trends underlying SA reporting but also of the demographics of survivors who seek treatment and evaluation after SA is vital, said Robert Glatter, MD, in an interview.

“Being able to better understand how social and societal movements affect a patient’s comfort in reporting an SA is vital in tracking the numbers of people who seek care in the ED,” said Dr. Glatter, an emergency medicine physician at Lenox Hill Hospital at Northwell Health, New York, and also of Hofstra University, Hempstead, N.Y.

Dr. Glatter said he was not surprised by the significant increase in sexual assault presentations, especially in light of increased awareness and the influence of the #MeToo movement and other social justice movements over the past decade.

“While I believe that victims of sexual violence may now feel more empowered to report an assault, the volume of SA that go unreported remains a serious public health issue and concern” in the United States and globally, he emphasized.

A key message from the current study is that there is a need for investment in “compassionate and comprehensive care for all survivors of SA,” Dr. Glatter said. “This includes recognition of the extensive mental health consequences of SA that can lead to not only depression, PTSD, and anxiety but also to suicidal ideation and suicide. The longer-term medical effects become life altering, permeating families and future generations,” he emphasized.

“As a society, we must also place a strong emphasis on caring for all SA survivors, but particularly those who come from economically or socially disadvantaged backgrounds who are uninsured or underinsured,” Dr. Glatter said. Issues of race, gender identity, and sexual identity among SA survivors also must be taken into consideration, he added.

“We need to better understand how our health care system can provide more nuanced follow-up care and reporting for survivors in outpatient settings. … Making access easier, while ensuring confidentiality, will allow more survivors of SA to seek treatment and care,” he said. “We also need to understand how using forensic nurses in this capacity, and beyond the ED, can better serve minority and racially diverse communities” and to increase the recruitment and training of such specialized nurses to care for SA victims, Dr. Glatter noted.

The study was supported by internal funding from the University of Michigan and the department of obstetrics and gynecology. Corresponding author Erica C. Marsh, MD, has received personal fees from Myovant Sciences and Pfizer unrelated to the current study. Dr. Glatter has disclosed no relevant financial relationships.

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

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Menopause appears to be an independent risk factor for relapse in women with schizophrenia spectrum disorders (SSDs), new research suggests.
 

Investigators studied a cohort of close to 62,000 people with SSDs, stratifying individuals by sex and age, and found that starting between the ages of 45 and 50 years – when the menopausal transition is underway – women were more frequently hospitalized for psychosis, compared with men and women younger than 45 years.

In addition, the protective effect of antipsychotic medication was highest in women younger than 45 years and lowest in women aged 45 years or older, even at higher doses.

“Women with schizophrenia who are older than 45 are a vulnerable group for relapse, and higher doses of antipsychotics are not the answer,” lead author Iris Sommer, MD, PhD, professor, department of neuroscience, University Medical Center of Groningen, the Netherlands, told this news organization.

The study was published online in Schizophrenia Bulletin.
 

Vulnerable period

There is an association between estrogen levels and disease severity throughout the life stages of women with SSDs, with lower estrogen levels associated with psychosis, for example, during low estrogenic phases of the menstrual cycle, the investigators note.

“After menopause, estrogen levels remain low, which is associated with a deterioration in the clinical course; therefore, women with SSD have sex-specific psychiatric needs that differ according to their life stage,” they add.

“Estrogens inhibit an important liver enzyme (cytochrome P-450 [CYP1A2]), which leads to higher blood levels of several antipsychotics like olanzapine and clozapine,” said Dr. Sommer. In addition, estrogens make the stomach less acidic, “leading to easier resorption of medication.”

As a clinician, Dr. Sommer said that she has “often witnessed a worsening of symptoms [of psychosis] after menopause.” As a researcher, she “knew that estrogens can have ameliorating effects on brain health, especially in schizophrenia.”

She and her colleagues were motivated to research the issue because there is a “remarkable paucity” of quantitative data on a “vulnerable period that all women with schizophrenia will experience.”
 

Detailed, quantitative data

The researchers sought to provide “detailed, quantitative data on life-stage dependent clinical changes occurring in women with SSD, using an intra-individual design to prevent confounding.”

They drew on data from a nationwide, register-based cohort study of all hospitalized patients with SSD between 1972 and 2014 in Finland (n = 61,889), with follow-up from Jan. 1, 1996, to Dec. 31, 2017.

People were stratified according to age (younger than 45 years and 45 years or older), with the same person contributing person-time to both age groups. The cohort was also subdivided into 5-year age groups, starting at age 20 years and ending at age 69 years.

The primary outcome measure was relapse (that is, inpatient hospitalization because of psychosis).

The researchers focused specifically on monotherapies, excluding time periods when two or more antipsychotics were used concomitantly. They also looked at antipsychotic nonuse periods.

Antipsychotic monotherapies were categorized into defined daily doses per day (DDDs/d):

• less than 0.4
• 0.4 to 0.6
• 0.6 to 0.9
• 0.9 to less than 1.1
• 1.1 to less than 1.4
• 1.4 to less than 1.6
• 1.6 or more

The researchers restricted the main analyses to the four most frequently used oral antipsychotic monotherapies: clozapine, olanzapine, quetiapine, and risperidone.
 

The turning tide

The cohort consisted of more men than women (31,104 vs. 30,785, respectively), with a mean (standard deviation) age of 49.8 (16.6) years in women vs. 43.6 (14.8) in men.

Among both sexes, olanzapine was the most prescribed antipsychotic (roughly one-quarter of patients). In women, the next most common antipsychotic was risperidone, followed by quetiapine and clozapine, whereas in men, the second most common antipsychotic was clozapine, followed by risperidone and quetiapine.

When the researchers compared men and women younger than 45 years, there were “few consistent differences” in proportions hospitalized for psychosis.

Starting at age 45 years and continuing through the oldest age group (65-69 years), higher proportions of women were hospitalized for psychosis, compared with their male peers (all Ps < .00001). 

Women 45 or older had significantly higher risk for relapse associated with standard dose use, compared with the other groups.

When the researchers compared men and women older and younger than 45 years, women younger than 45 years showed lower adjusted hazard ratios (aHRs) at doses between of 0.6-0.9 DDDs/d, whereas for doses over 1.1 DDDs/d, women aged 45 years or older showed “remarkably higher” aHRs, compared with women younger than 45 years and men aged 45 years or older, with a difference that increased with increasing dose.

In women, the efficacy of the antipsychotics was decreased at these DDDs/d.

“We ... showed that antipsychotic monotherapy is most effective in preventing relapse in women below 45, as compared to women above that age, and also as compared to men of all ages,” the authors summarize. But after age 45 years, “the tide seems to turn for women,” compared with younger women and with men of the same age group.

One of several study limitations was the use of age as an estimation of menopausal status, they note.
 

Don’t just raise the dose

Commenting on the research, Mary Seeman, MD, professor emerita, department of psychiatry, University of Toronto, noted the study corroborates her group’s findings regarding the effect of menopause on antipsychotic response.

“When the efficacy of previously effective antipsychotic doses wanes at menopause, raising the dose is not the treatment of choice because it increases the risk of weight gain, cardiovascular, and cerebrovascular events,” said Dr. Seeman, who was not involved with the current research.

“Changing to an antipsychotic that is less affected by estrogen loss may work better,” she continued, noting that amisulpride and aripiprazole “work well post menopause.”

Additional interventions may include changing to a depot or skin-patch antipsychotic that “obviates first-pass metabolism,” adding hormone replacement or a selective estrogen receptor modulator or including phytoestrogens (bioidenticals) in the diet.

The study yields research recommendations, including comparing the effectiveness of different antipsychotics in postmenopausal women with SSDs, recruiting pre- and postmenopausal women in trials of antipsychotic drugs, and stratifying by hormonal status when analyzing results of antipsychotic trials, Dr. Seeman said.

This work was supported by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital and the Academy of Finland. The Dutch Medical Research Association supported Dr. Sommer. Dr. Sommer declares no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Seeman declares no relevant financial relationships.

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

Menopause appears to be an independent risk factor for relapse in women with schizophrenia spectrum disorders (SSDs), new research suggests.
 

Investigators studied a cohort of close to 62,000 people with SSDs, stratifying individuals by sex and age, and found that starting between the ages of 45 and 50 years – when the menopausal transition is underway – women were more frequently hospitalized for psychosis, compared with men and women younger than 45 years.

In addition, the protective effect of antipsychotic medication was highest in women younger than 45 years and lowest in women aged 45 years or older, even at higher doses.

“Women with schizophrenia who are older than 45 are a vulnerable group for relapse, and higher doses of antipsychotics are not the answer,” lead author Iris Sommer, MD, PhD, professor, department of neuroscience, University Medical Center of Groningen, the Netherlands, told this news organization.

The study was published online in Schizophrenia Bulletin.
 

Vulnerable period

There is an association between estrogen levels and disease severity throughout the life stages of women with SSDs, with lower estrogen levels associated with psychosis, for example, during low estrogenic phases of the menstrual cycle, the investigators note.

“After menopause, estrogen levels remain low, which is associated with a deterioration in the clinical course; therefore, women with SSD have sex-specific psychiatric needs that differ according to their life stage,” they add.

“Estrogens inhibit an important liver enzyme (cytochrome P-450 [CYP1A2]), which leads to higher blood levels of several antipsychotics like olanzapine and clozapine,” said Dr. Sommer. In addition, estrogens make the stomach less acidic, “leading to easier resorption of medication.”

As a clinician, Dr. Sommer said that she has “often witnessed a worsening of symptoms [of psychosis] after menopause.” As a researcher, she “knew that estrogens can have ameliorating effects on brain health, especially in schizophrenia.”

She and her colleagues were motivated to research the issue because there is a “remarkable paucity” of quantitative data on a “vulnerable period that all women with schizophrenia will experience.”
 

Detailed, quantitative data

The researchers sought to provide “detailed, quantitative data on life-stage dependent clinical changes occurring in women with SSD, using an intra-individual design to prevent confounding.”

They drew on data from a nationwide, register-based cohort study of all hospitalized patients with SSD between 1972 and 2014 in Finland (n = 61,889), with follow-up from Jan. 1, 1996, to Dec. 31, 2017.

People were stratified according to age (younger than 45 years and 45 years or older), with the same person contributing person-time to both age groups. The cohort was also subdivided into 5-year age groups, starting at age 20 years and ending at age 69 years.

The primary outcome measure was relapse (that is, inpatient hospitalization because of psychosis).

The researchers focused specifically on monotherapies, excluding time periods when two or more antipsychotics were used concomitantly. They also looked at antipsychotic nonuse periods.

Antipsychotic monotherapies were categorized into defined daily doses per day (DDDs/d):

• less than 0.4
• 0.4 to 0.6
• 0.6 to 0.9
• 0.9 to less than 1.1
• 1.1 to less than 1.4
• 1.4 to less than 1.6
• 1.6 or more

The researchers restricted the main analyses to the four most frequently used oral antipsychotic monotherapies: clozapine, olanzapine, quetiapine, and risperidone.
 

The turning tide

The cohort consisted of more men than women (31,104 vs. 30,785, respectively), with a mean (standard deviation) age of 49.8 (16.6) years in women vs. 43.6 (14.8) in men.

Among both sexes, olanzapine was the most prescribed antipsychotic (roughly one-quarter of patients). In women, the next most common antipsychotic was risperidone, followed by quetiapine and clozapine, whereas in men, the second most common antipsychotic was clozapine, followed by risperidone and quetiapine.

When the researchers compared men and women younger than 45 years, there were “few consistent differences” in proportions hospitalized for psychosis.

Starting at age 45 years and continuing through the oldest age group (65-69 years), higher proportions of women were hospitalized for psychosis, compared with their male peers (all Ps < .00001). 

Women 45 or older had significantly higher risk for relapse associated with standard dose use, compared with the other groups.

When the researchers compared men and women older and younger than 45 years, women younger than 45 years showed lower adjusted hazard ratios (aHRs) at doses between of 0.6-0.9 DDDs/d, whereas for doses over 1.1 DDDs/d, women aged 45 years or older showed “remarkably higher” aHRs, compared with women younger than 45 years and men aged 45 years or older, with a difference that increased with increasing dose.

In women, the efficacy of the antipsychotics was decreased at these DDDs/d.

“We ... showed that antipsychotic monotherapy is most effective in preventing relapse in women below 45, as compared to women above that age, and also as compared to men of all ages,” the authors summarize. But after age 45 years, “the tide seems to turn for women,” compared with younger women and with men of the same age group.

One of several study limitations was the use of age as an estimation of menopausal status, they note.
 

Don’t just raise the dose

Commenting on the research, Mary Seeman, MD, professor emerita, department of psychiatry, University of Toronto, noted the study corroborates her group’s findings regarding the effect of menopause on antipsychotic response.

“When the efficacy of previously effective antipsychotic doses wanes at menopause, raising the dose is not the treatment of choice because it increases the risk of weight gain, cardiovascular, and cerebrovascular events,” said Dr. Seeman, who was not involved with the current research.

“Changing to an antipsychotic that is less affected by estrogen loss may work better,” she continued, noting that amisulpride and aripiprazole “work well post menopause.”

Additional interventions may include changing to a depot or skin-patch antipsychotic that “obviates first-pass metabolism,” adding hormone replacement or a selective estrogen receptor modulator or including phytoestrogens (bioidenticals) in the diet.

The study yields research recommendations, including comparing the effectiveness of different antipsychotics in postmenopausal women with SSDs, recruiting pre- and postmenopausal women in trials of antipsychotic drugs, and stratifying by hormonal status when analyzing results of antipsychotic trials, Dr. Seeman said.

This work was supported by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital and the Academy of Finland. The Dutch Medical Research Association supported Dr. Sommer. Dr. Sommer declares no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Seeman declares no relevant financial relationships.

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

Menopause appears to be an independent risk factor for relapse in women with schizophrenia spectrum disorders (SSDs), new research suggests.
 

Investigators studied a cohort of close to 62,000 people with SSDs, stratifying individuals by sex and age, and found that starting between the ages of 45 and 50 years – when the menopausal transition is underway – women were more frequently hospitalized for psychosis, compared with men and women younger than 45 years.

In addition, the protective effect of antipsychotic medication was highest in women younger than 45 years and lowest in women aged 45 years or older, even at higher doses.

“Women with schizophrenia who are older than 45 are a vulnerable group for relapse, and higher doses of antipsychotics are not the answer,” lead author Iris Sommer, MD, PhD, professor, department of neuroscience, University Medical Center of Groningen, the Netherlands, told this news organization.

The study was published online in Schizophrenia Bulletin.
 

Vulnerable period

There is an association between estrogen levels and disease severity throughout the life stages of women with SSDs, with lower estrogen levels associated with psychosis, for example, during low estrogenic phases of the menstrual cycle, the investigators note.

“After menopause, estrogen levels remain low, which is associated with a deterioration in the clinical course; therefore, women with SSD have sex-specific psychiatric needs that differ according to their life stage,” they add.

“Estrogens inhibit an important liver enzyme (cytochrome P-450 [CYP1A2]), which leads to higher blood levels of several antipsychotics like olanzapine and clozapine,” said Dr. Sommer. In addition, estrogens make the stomach less acidic, “leading to easier resorption of medication.”

As a clinician, Dr. Sommer said that she has “often witnessed a worsening of symptoms [of psychosis] after menopause.” As a researcher, she “knew that estrogens can have ameliorating effects on brain health, especially in schizophrenia.”

She and her colleagues were motivated to research the issue because there is a “remarkable paucity” of quantitative data on a “vulnerable period that all women with schizophrenia will experience.”
 

Detailed, quantitative data

The researchers sought to provide “detailed, quantitative data on life-stage dependent clinical changes occurring in women with SSD, using an intra-individual design to prevent confounding.”

They drew on data from a nationwide, register-based cohort study of all hospitalized patients with SSD between 1972 and 2014 in Finland (n = 61,889), with follow-up from Jan. 1, 1996, to Dec. 31, 2017.

People were stratified according to age (younger than 45 years and 45 years or older), with the same person contributing person-time to both age groups. The cohort was also subdivided into 5-year age groups, starting at age 20 years and ending at age 69 years.

The primary outcome measure was relapse (that is, inpatient hospitalization because of psychosis).

The researchers focused specifically on monotherapies, excluding time periods when two or more antipsychotics were used concomitantly. They also looked at antipsychotic nonuse periods.

Antipsychotic monotherapies were categorized into defined daily doses per day (DDDs/d):

• less than 0.4
• 0.4 to 0.6
• 0.6 to 0.9
• 0.9 to less than 1.1
• 1.1 to less than 1.4
• 1.4 to less than 1.6
• 1.6 or more

The researchers restricted the main analyses to the four most frequently used oral antipsychotic monotherapies: clozapine, olanzapine, quetiapine, and risperidone.
 

The turning tide

The cohort consisted of more men than women (31,104 vs. 30,785, respectively), with a mean (standard deviation) age of 49.8 (16.6) years in women vs. 43.6 (14.8) in men.

Among both sexes, olanzapine was the most prescribed antipsychotic (roughly one-quarter of patients). In women, the next most common antipsychotic was risperidone, followed by quetiapine and clozapine, whereas in men, the second most common antipsychotic was clozapine, followed by risperidone and quetiapine.

When the researchers compared men and women younger than 45 years, there were “few consistent differences” in proportions hospitalized for psychosis.

Starting at age 45 years and continuing through the oldest age group (65-69 years), higher proportions of women were hospitalized for psychosis, compared with their male peers (all Ps < .00001). 

Women 45 or older had significantly higher risk for relapse associated with standard dose use, compared with the other groups.

When the researchers compared men and women older and younger than 45 years, women younger than 45 years showed lower adjusted hazard ratios (aHRs) at doses between of 0.6-0.9 DDDs/d, whereas for doses over 1.1 DDDs/d, women aged 45 years or older showed “remarkably higher” aHRs, compared with women younger than 45 years and men aged 45 years or older, with a difference that increased with increasing dose.

In women, the efficacy of the antipsychotics was decreased at these DDDs/d.

“We ... showed that antipsychotic monotherapy is most effective in preventing relapse in women below 45, as compared to women above that age, and also as compared to men of all ages,” the authors summarize. But after age 45 years, “the tide seems to turn for women,” compared with younger women and with men of the same age group.

One of several study limitations was the use of age as an estimation of menopausal status, they note.
 

Don’t just raise the dose

Commenting on the research, Mary Seeman, MD, professor emerita, department of psychiatry, University of Toronto, noted the study corroborates her group’s findings regarding the effect of menopause on antipsychotic response.

“When the efficacy of previously effective antipsychotic doses wanes at menopause, raising the dose is not the treatment of choice because it increases the risk of weight gain, cardiovascular, and cerebrovascular events,” said Dr. Seeman, who was not involved with the current research.

“Changing to an antipsychotic that is less affected by estrogen loss may work better,” she continued, noting that amisulpride and aripiprazole “work well post menopause.”

Additional interventions may include changing to a depot or skin-patch antipsychotic that “obviates first-pass metabolism,” adding hormone replacement or a selective estrogen receptor modulator or including phytoestrogens (bioidenticals) in the diet.

The study yields research recommendations, including comparing the effectiveness of different antipsychotics in postmenopausal women with SSDs, recruiting pre- and postmenopausal women in trials of antipsychotic drugs, and stratifying by hormonal status when analyzing results of antipsychotic trials, Dr. Seeman said.

This work was supported by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital and the Academy of Finland. The Dutch Medical Research Association supported Dr. Sommer. Dr. Sommer declares no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Seeman declares no relevant financial relationships.

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

Drugs commonly used to treat erectile dysfunction (ED) are not associated with a decreased risk of Alzheimer’s disease and related dementias (ADRD), new research shows.

The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.

The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.

“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.

The new study was published online in Brain Communications.


 

Not the final word?

Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*

Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.

The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.

In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.

The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.

“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
 

Impressive study design

Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.

“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”

The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.

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

Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.

Drugs commonly used to treat erectile dysfunction (ED) are not associated with a decreased risk of Alzheimer’s disease and related dementias (ADRD), new research shows.

The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.

The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.

“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.

The new study was published online in Brain Communications.


 

Not the final word?

Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*

Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.

The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.

In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.

The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.

“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
 

Impressive study design

Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.

“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”

The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.

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

Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.

Drugs commonly used to treat erectile dysfunction (ED) are not associated with a decreased risk of Alzheimer’s disease and related dementias (ADRD), new research shows.

The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.

The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.

“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.

The new study was published online in Brain Communications.


 

Not the final word?

Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*

Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.

The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.

In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.

The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.

“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
 

Impressive study design

Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.

“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”

The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.

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

Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.

Listening to birdsong appears to have a positive and significant impact on mental health and mood, new research suggests.

Investigators found that people who listened to recordings of birds singing experienced a significant reduction in anxiety and paranoia. In contrast, the researchers also found that recordings of traffic noises, including car engines, sirens, and construction, increased depressive states.

“The results suggest that it may be worthwhile to investigate the targeted use of natural sounds such as birdsong in a clinical setting – for example, in hospital waiting rooms or in psychiatric settings,” study investigator Emil Stobbe, MSc, a predoctoral fellow at the Max Planck Institute for Human Development, Berlin, said in an interview.

“If someone is seeking an easily accessible intervention to lower distress, listening to an audio clip of birds singing might be a great option,” he added.

The study was published online in Scientific Reports.
 

Nature’s calming effect

The aim of the research was “to investigate how the physical environment impact brain and mental health,” Mr. Stobbe said.

Mr. Stobbe said that there is significantly more research examining visual properties of the physical environment but that the auditory domain is not as well researched, although, he added, that the beneficial effects of interactions with nature are “well studied.”

He noted that anxiety and paranoia can be experienced by many individuals even though they may be unaware that they are experiencing these states.

“We wanted to investigate if the beneficial effects of nature can also exert their impact on these states. In theory, birds can be representational for natural and vital environment, which, in turn, transfer the positive effects of nature on birdsong listeners,” he said.

A previous study compared nature versus city soundscape conditions and showed that the nature soundscape improved participants’ cognitive performance but did not improve mood. The present study added diversity to the soundscapes and focused not only on cognition and general mood but also on state paranoia, “which can be measured in a change-sensitive manner” and “has been shown to increase in response to traffic noise.”

The researchers hypothesized that birdsong would have a greater beneficial effect on mood and paranoia and on cognitive performance compared with traffic noise. They also investigated whether greater versus lower diversity of bird species or noise sources within the soundscapes “would be a relevant factor modulating the effects.”

The researchers recruited participants (n = 295) from a crowdsourcing platform. Participants’ mean age was late 20s (standard deviations ranged from 6.30 to 7.72), with a greater proportion of male versus female participants.

To be included, participants were required to have no history of mental illness, hearing difficulties, substance/drug intake, or suicidal thoughts/tendencies.

The outcomes of interest (mood, paranoia, cognitive performance) were measured before and after soundscape exposure and each soundscape had a low- versus high-diversity version. This resulted in several analyses that compared two types of sounds (birdsongs vs. traffic noise) x two levels of diversity (low vs. high diversity) and two time points (pre- vs. post exposure).

The exposure to sounds lasted for 6 minutes, after which they were asked to report (on a 0-100 visual scale) how diverse/monotone, beautiful, and pleasant they perceived the soundscape to be.
 

Reduction in depressive symptoms

Participants were divided into four groups: low-diversity traffic noise soundscape (n = 83), high-diversity traffic noise soundscape (n = 60), low-diversity birdsong soundscape (n = 63), and high-diversity birdsong soundscape (n = 80)

In addition to listening to the sounds, participants completed questionnaires measuring mood (depression and anxiety) and paranoia as well as a test of digit span cognitive performance (both the forward and the backward versions).

The type, diversity, and type x diversity all revealed significant effect sizes (F[3, 276] = 78.6; P < .001; eta-squared = 0.461; F[3, 276] = 3.16; P = .025; eta-squared = 0.033; and F[3, 276] = 2.66; P = .028, respectively), “suggesting that all of these factors, as well as their interaction, had a significant impact on the perception of soundscapes (that is, ratings on monotony/diversity, beauty, and pleasantness).”

A post hoc examination showed that depressive symptoms significantly increased within the low- and high-diversity urban soundscapes but decreased significantly in the high-diversity birdsong soundscapes (T[1, 60] = –2.57; P = .012; d = –0.29).

For anxiety, the post hoc within-group analyses found no effects within low- and high-diversity traffic noise conditions (T[1, 82] = –1.37; P = .174; d = –0.15 and T[1, 68] = 0.49; P = .629; d = 0.06, respectively). By contrast, there were significant declines in both birdsong conditions (low diversity: T[1, 62] = –6.13; P < .001; d = –0.77; high diversity: T[1, 60] = –6.32; P < .001; d =  –0.70).

Similarly, there were no changes in participants with paranoia when they listened to either low- or high-diversity traffic noises (T[1, 82] = –0.55; P = .583; d = –0.06 and T[1, 68] = 0.67; P = .507; d = 0.08, respectively). On the other hand, both birdsong conditions yielded reductions in paranoia (low diversity: T[1, 62] = –5.90; P < .001; d = –0.74; high diversity: T[1, 60] =  –4.11; P < .001; d = –0.46).

None of the soundscapes had any effect on cognition.

“In theory, birds can be representational for natural and vital environments which, in turn, transfer the positive effects of nature on birdsong listeners,” said Mr. Stobbe.

“Taken together, the findings of the current study provide another facet of why interactions with nature can be beneficial for our mental health, and it is highly important to preserve nature,” he added.

Mr. Stobbe said that future research should focus on investigating mixed soundscapes including examining whether the presence of natural sounds in urban settings lower stressors such as traffic noise.
 

An understudied area

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness called the study “interesting but limited.”

Dr. Duckworth, who was not involved in the research said that the “benefits of nature are understudied” and agreed with the investigators that it is potentially important to study the use of birdsongs in psychiatric facilities. “Future studies could also correlate the role of birdsong with the mental health benefits/aspects of ‘being in nature,’ which has been found to have some effect.”

Open Access funding was enabled and organized by Projekt DEAL. The authors and Dr. Duckworth declared no competing interests.

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

Listening to birdsong appears to have a positive and significant impact on mental health and mood, new research suggests.

Investigators found that people who listened to recordings of birds singing experienced a significant reduction in anxiety and paranoia. In contrast, the researchers also found that recordings of traffic noises, including car engines, sirens, and construction, increased depressive states.

“The results suggest that it may be worthwhile to investigate the targeted use of natural sounds such as birdsong in a clinical setting – for example, in hospital waiting rooms or in psychiatric settings,” study investigator Emil Stobbe, MSc, a predoctoral fellow at the Max Planck Institute for Human Development, Berlin, said in an interview.

“If someone is seeking an easily accessible intervention to lower distress, listening to an audio clip of birds singing might be a great option,” he added.

The study was published online in Scientific Reports.
 

Nature’s calming effect

The aim of the research was “to investigate how the physical environment impact brain and mental health,” Mr. Stobbe said.

Mr. Stobbe said that there is significantly more research examining visual properties of the physical environment but that the auditory domain is not as well researched, although, he added, that the beneficial effects of interactions with nature are “well studied.”

He noted that anxiety and paranoia can be experienced by many individuals even though they may be unaware that they are experiencing these states.

“We wanted to investigate if the beneficial effects of nature can also exert their impact on these states. In theory, birds can be representational for natural and vital environment, which, in turn, transfer the positive effects of nature on birdsong listeners,” he said.

A previous study compared nature versus city soundscape conditions and showed that the nature soundscape improved participants’ cognitive performance but did not improve mood. The present study added diversity to the soundscapes and focused not only on cognition and general mood but also on state paranoia, “which can be measured in a change-sensitive manner” and “has been shown to increase in response to traffic noise.”

The researchers hypothesized that birdsong would have a greater beneficial effect on mood and paranoia and on cognitive performance compared with traffic noise. They also investigated whether greater versus lower diversity of bird species or noise sources within the soundscapes “would be a relevant factor modulating the effects.”

The researchers recruited participants (n = 295) from a crowdsourcing platform. Participants’ mean age was late 20s (standard deviations ranged from 6.30 to 7.72), with a greater proportion of male versus female participants.

To be included, participants were required to have no history of mental illness, hearing difficulties, substance/drug intake, or suicidal thoughts/tendencies.

The outcomes of interest (mood, paranoia, cognitive performance) were measured before and after soundscape exposure and each soundscape had a low- versus high-diversity version. This resulted in several analyses that compared two types of sounds (birdsongs vs. traffic noise) x two levels of diversity (low vs. high diversity) and two time points (pre- vs. post exposure).

The exposure to sounds lasted for 6 minutes, after which they were asked to report (on a 0-100 visual scale) how diverse/monotone, beautiful, and pleasant they perceived the soundscape to be.
 

Reduction in depressive symptoms

Participants were divided into four groups: low-diversity traffic noise soundscape (n = 83), high-diversity traffic noise soundscape (n = 60), low-diversity birdsong soundscape (n = 63), and high-diversity birdsong soundscape (n = 80)

In addition to listening to the sounds, participants completed questionnaires measuring mood (depression and anxiety) and paranoia as well as a test of digit span cognitive performance (both the forward and the backward versions).

The type, diversity, and type x diversity all revealed significant effect sizes (F[3, 276] = 78.6; P < .001; eta-squared = 0.461; F[3, 276] = 3.16; P = .025; eta-squared = 0.033; and F[3, 276] = 2.66; P = .028, respectively), “suggesting that all of these factors, as well as their interaction, had a significant impact on the perception of soundscapes (that is, ratings on monotony/diversity, beauty, and pleasantness).”

A post hoc examination showed that depressive symptoms significantly increased within the low- and high-diversity urban soundscapes but decreased significantly in the high-diversity birdsong soundscapes (T[1, 60] = –2.57; P = .012; d = –0.29).

For anxiety, the post hoc within-group analyses found no effects within low- and high-diversity traffic noise conditions (T[1, 82] = –1.37; P = .174; d = –0.15 and T[1, 68] = 0.49; P = .629; d = 0.06, respectively). By contrast, there were significant declines in both birdsong conditions (low diversity: T[1, 62] = –6.13; P < .001; d = –0.77; high diversity: T[1, 60] = –6.32; P < .001; d =  –0.70).

Similarly, there were no changes in participants with paranoia when they listened to either low- or high-diversity traffic noises (T[1, 82] = –0.55; P = .583; d = –0.06 and T[1, 68] = 0.67; P = .507; d = 0.08, respectively). On the other hand, both birdsong conditions yielded reductions in paranoia (low diversity: T[1, 62] = –5.90; P < .001; d = –0.74; high diversity: T[1, 60] =  –4.11; P < .001; d = –0.46).

None of the soundscapes had any effect on cognition.

“In theory, birds can be representational for natural and vital environments which, in turn, transfer the positive effects of nature on birdsong listeners,” said Mr. Stobbe.

“Taken together, the findings of the current study provide another facet of why interactions with nature can be beneficial for our mental health, and it is highly important to preserve nature,” he added.

Mr. Stobbe said that future research should focus on investigating mixed soundscapes including examining whether the presence of natural sounds in urban settings lower stressors such as traffic noise.
 

An understudied area

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness called the study “interesting but limited.”

Dr. Duckworth, who was not involved in the research said that the “benefits of nature are understudied” and agreed with the investigators that it is potentially important to study the use of birdsongs in psychiatric facilities. “Future studies could also correlate the role of birdsong with the mental health benefits/aspects of ‘being in nature,’ which has been found to have some effect.”

Open Access funding was enabled and organized by Projekt DEAL. The authors and Dr. Duckworth declared no competing interests.

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

Listening to birdsong appears to have a positive and significant impact on mental health and mood, new research suggests.

Investigators found that people who listened to recordings of birds singing experienced a significant reduction in anxiety and paranoia. In contrast, the researchers also found that recordings of traffic noises, including car engines, sirens, and construction, increased depressive states.

“The results suggest that it may be worthwhile to investigate the targeted use of natural sounds such as birdsong in a clinical setting – for example, in hospital waiting rooms or in psychiatric settings,” study investigator Emil Stobbe, MSc, a predoctoral fellow at the Max Planck Institute for Human Development, Berlin, said in an interview.

“If someone is seeking an easily accessible intervention to lower distress, listening to an audio clip of birds singing might be a great option,” he added.

The study was published online in Scientific Reports.
 

Nature’s calming effect

The aim of the research was “to investigate how the physical environment impact brain and mental health,” Mr. Stobbe said.

Mr. Stobbe said that there is significantly more research examining visual properties of the physical environment but that the auditory domain is not as well researched, although, he added, that the beneficial effects of interactions with nature are “well studied.”

He noted that anxiety and paranoia can be experienced by many individuals even though they may be unaware that they are experiencing these states.

“We wanted to investigate if the beneficial effects of nature can also exert their impact on these states. In theory, birds can be representational for natural and vital environment, which, in turn, transfer the positive effects of nature on birdsong listeners,” he said.

A previous study compared nature versus city soundscape conditions and showed that the nature soundscape improved participants’ cognitive performance but did not improve mood. The present study added diversity to the soundscapes and focused not only on cognition and general mood but also on state paranoia, “which can be measured in a change-sensitive manner” and “has been shown to increase in response to traffic noise.”

The researchers hypothesized that birdsong would have a greater beneficial effect on mood and paranoia and on cognitive performance compared with traffic noise. They also investigated whether greater versus lower diversity of bird species or noise sources within the soundscapes “would be a relevant factor modulating the effects.”

The researchers recruited participants (n = 295) from a crowdsourcing platform. Participants’ mean age was late 20s (standard deviations ranged from 6.30 to 7.72), with a greater proportion of male versus female participants.

To be included, participants were required to have no history of mental illness, hearing difficulties, substance/drug intake, or suicidal thoughts/tendencies.

The outcomes of interest (mood, paranoia, cognitive performance) were measured before and after soundscape exposure and each soundscape had a low- versus high-diversity version. This resulted in several analyses that compared two types of sounds (birdsongs vs. traffic noise) x two levels of diversity (low vs. high diversity) and two time points (pre- vs. post exposure).

The exposure to sounds lasted for 6 minutes, after which they were asked to report (on a 0-100 visual scale) how diverse/monotone, beautiful, and pleasant they perceived the soundscape to be.
 

Reduction in depressive symptoms

Participants were divided into four groups: low-diversity traffic noise soundscape (n = 83), high-diversity traffic noise soundscape (n = 60), low-diversity birdsong soundscape (n = 63), and high-diversity birdsong soundscape (n = 80)

In addition to listening to the sounds, participants completed questionnaires measuring mood (depression and anxiety) and paranoia as well as a test of digit span cognitive performance (both the forward and the backward versions).

The type, diversity, and type x diversity all revealed significant effect sizes (F[3, 276] = 78.6; P < .001; eta-squared = 0.461; F[3, 276] = 3.16; P = .025; eta-squared = 0.033; and F[3, 276] = 2.66; P = .028, respectively), “suggesting that all of these factors, as well as their interaction, had a significant impact on the perception of soundscapes (that is, ratings on monotony/diversity, beauty, and pleasantness).”

A post hoc examination showed that depressive symptoms significantly increased within the low- and high-diversity urban soundscapes but decreased significantly in the high-diversity birdsong soundscapes (T[1, 60] = –2.57; P = .012; d = –0.29).

For anxiety, the post hoc within-group analyses found no effects within low- and high-diversity traffic noise conditions (T[1, 82] = –1.37; P = .174; d = –0.15 and T[1, 68] = 0.49; P = .629; d = 0.06, respectively). By contrast, there were significant declines in both birdsong conditions (low diversity: T[1, 62] = –6.13; P < .001; d = –0.77; high diversity: T[1, 60] = –6.32; P < .001; d =  –0.70).

Similarly, there were no changes in participants with paranoia when they listened to either low- or high-diversity traffic noises (T[1, 82] = –0.55; P = .583; d = –0.06 and T[1, 68] = 0.67; P = .507; d = 0.08, respectively). On the other hand, both birdsong conditions yielded reductions in paranoia (low diversity: T[1, 62] = –5.90; P < .001; d = –0.74; high diversity: T[1, 60] =  –4.11; P < .001; d = –0.46).

None of the soundscapes had any effect on cognition.

“In theory, birds can be representational for natural and vital environments which, in turn, transfer the positive effects of nature on birdsong listeners,” said Mr. Stobbe.

“Taken together, the findings of the current study provide another facet of why interactions with nature can be beneficial for our mental health, and it is highly important to preserve nature,” he added.

Mr. Stobbe said that future research should focus on investigating mixed soundscapes including examining whether the presence of natural sounds in urban settings lower stressors such as traffic noise.
 

An understudied area

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness called the study “interesting but limited.”

Dr. Duckworth, who was not involved in the research said that the “benefits of nature are understudied” and agreed with the investigators that it is potentially important to study the use of birdsongs in psychiatric facilities. “Future studies could also correlate the role of birdsong with the mental health benefits/aspects of ‘being in nature,’ which has been found to have some effect.”

Open Access funding was enabled and organized by Projekt DEAL. The authors and Dr. Duckworth declared no competing interests.

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