Clinical Psychiatry News

New research provides more evidence that tau plasma biomarkers associated with Alzheimer’s disease can be skewed by chronic kidney disease and suggests that using ratios of these biomarkers can attenuate the skewed results.

In a cross-sectional study of adults with and those without cognitive impairment, chronic kidney disease was associated with increased plasma concentrations of phosphorylated tau (p-tau) 217 and 181.

However, there were no associations between chronic kidney disease and the ratio of p-tau217 to unphosphorylated tau 217 (pT217/T217), and the associations with p-tau181 to unphosphorylated tau 181 (pT181/T181) were attenuated in patients with cognitive impairment.

“These novel findings suggest that plasma measures of the phosphorylated to unphosphorylated tau ratios are more accurate than p-tau forms alone as they correlate less with individual difference in glomerular filtration rate or impaired kidney function,” reported an investigative team led by Oskar Hansson, MD, PhD, with Lund University in Sweden.

“Thus, to mitigate the effects of non-Alzheimer’s–related comorbidities like chronic kidney disease on the performance of plasma Alzheimer’s disease biomarkers, certain tau ratios, and specifically pT217/T217, should be considered for implementation in clinical practice and drug trials,” they added.

The study was published online in JAMA Neurology to coincide with a presentation at the International Conference on Alzheimer’s and Parkinson’s Diseases in Gothenburg, Sweden.


 

Skewed tau levels

Plasma biomarkers of amyloid-beta (Abeta) and tau pathologies, and in particular variants in p-tau217 and p-tau181, have shown promise for use in Alzheimer’s disease diagnosis and prognosis. However, previous reports have suggested that chronic kidney disease might influence plasma p-tau217 and p-tau181 concentrations, potentially decreasing their usefulness in the diagnostic workup of dementia.

Researchers investigated associations of chronic kidney disease with plasma ratios of p-tau217 and p-tau181 to the corresponding unphosphorylated peptides in Alzheimer’s disease.

The data came from 473 older adults, with and without cognitive impairment, from the Swedish BioFinder-2 study who had plasma tau assessments and chronic kidney disease status established within 6 months of plasma collection.

The researchers found that lower estimated glomerular filtration rate levels (indicative of kidney dysfunction) were associated with higher plasma concentrations of phosphorylated and unphosphorylated tau peptides measured simultaneously using the tau immunoprecipitation mass spectrometry assay.

However, the correlations with estimated glomerular filtration rate were nonsignificant for the pT217/T217 ratio in individuals with cognitive impairment and were significantly attenuated for pT217/T217 in cognitively unimpaired individuals and for pT181/T181 in both cognitively unimpaired and impaired individuals.

“Importantly, we demonstrate that there were no significant associations between chronic kidney disease and the pT217/T217 ratio and changes in plasma pT181/T181 associated with chronic kidney disease were small or nonsignificant,” the researchers noted.

“Our results indicate that by using p-tau/tau ratios we may be able to reduce the variability in plasma p-tau levels driven by impaired kidney function and consequently such ratios are more robust measures of brain p-tau pathology in individuals with both early- and later-stage Alzheimer’s disease,” they added.

The researchers believe this is likely true for the ratios of other related proteins – a view that is supported by findings of attenuated associations of chronic kidney disease with Abeta42/40, compared with Abeta42 and Abeta40 in the current study and in previous studies.
 

Important clinical implications

Reached for comment, Rebecca Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, noted that research continues to indicate that blood biomarkers have “promise for improving, and possibly even redefining, the clinical workup for Alzheimer’s disease.

“Many of the Alzheimer’s blood tests in development today have focused on core blood biomarkers associated with amyloid accumulation and tau tangle formation in the brain,” Dr. Edelmayer said.

“Before these tests can be used more broadly in the clinic, we need to understand all of the variables that may impact the results of various blood biomarkers, including differences that may be driven by race, ethnicity, sex, and underlying health conditions, such as chronic kidney disease.

“This study corroborates other research suggesting that some Alzheimer’s-associated markers can be affected by chronic kidney disease, but by using ratios of amyloid or tau markers, we may be able to minimize these differences in results caused by underlying disease,” Dr. Edelmayer said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said, “Using these ratios makes a lot of sense because the ratios wouldn’t change with kidney function. I think this is an important advance in clinical utilization of these tests.”

Dr. Fillit noted that older people often have declining kidney function, which can be easily measured by glomerular filtration rate. Changes in blood levels of these markers with declining kidney function are “not unexpected, but [it’s] important that it’s been demonstrated.

“As we go forward, maybe the future utilization of these tests will be not only recording the ratios but also reporting the ratios in the context of somebody’s glomerular filtration rate. You could imagine a scenario where when the test is done, it’s automatically done alongside of glomerular filtration rate,” Dr. Fillit said in an interview.

The study was supported by Coins for Alzheimer’s Research Trust, the Tracy Family Stable Isotope Labeling Quantitation Center, and the National Institute of Neurological Disorders and Stroke. Dr. Hansson has received support to his institution from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche; consultancy/speaker fees from Amylyx, Alzpath, Biogen, Cerveau, Fujirebio, Genentech, Novartis, Roche, and Siemens; and personal fees from Eli Lilly, Eisai, Bioarctic, and Biogen outside the submitted work. Dr. Edelmayer and Dr. Fillit have disclosed no relevant financial relationships.

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

New research provides more evidence that tau plasma biomarkers associated with Alzheimer’s disease can be skewed by chronic kidney disease and suggests that using ratios of these biomarkers can attenuate the skewed results.

In a cross-sectional study of adults with and those without cognitive impairment, chronic kidney disease was associated with increased plasma concentrations of phosphorylated tau (p-tau) 217 and 181.

However, there were no associations between chronic kidney disease and the ratio of p-tau217 to unphosphorylated tau 217 (pT217/T217), and the associations with p-tau181 to unphosphorylated tau 181 (pT181/T181) were attenuated in patients with cognitive impairment.

“These novel findings suggest that plasma measures of the phosphorylated to unphosphorylated tau ratios are more accurate than p-tau forms alone as they correlate less with individual difference in glomerular filtration rate or impaired kidney function,” reported an investigative team led by Oskar Hansson, MD, PhD, with Lund University in Sweden.

“Thus, to mitigate the effects of non-Alzheimer’s–related comorbidities like chronic kidney disease on the performance of plasma Alzheimer’s disease biomarkers, certain tau ratios, and specifically pT217/T217, should be considered for implementation in clinical practice and drug trials,” they added.

The study was published online in JAMA Neurology to coincide with a presentation at the International Conference on Alzheimer’s and Parkinson’s Diseases in Gothenburg, Sweden.


 

Skewed tau levels

Plasma biomarkers of amyloid-beta (Abeta) and tau pathologies, and in particular variants in p-tau217 and p-tau181, have shown promise for use in Alzheimer’s disease diagnosis and prognosis. However, previous reports have suggested that chronic kidney disease might influence plasma p-tau217 and p-tau181 concentrations, potentially decreasing their usefulness in the diagnostic workup of dementia.

Researchers investigated associations of chronic kidney disease with plasma ratios of p-tau217 and p-tau181 to the corresponding unphosphorylated peptides in Alzheimer’s disease.

The data came from 473 older adults, with and without cognitive impairment, from the Swedish BioFinder-2 study who had plasma tau assessments and chronic kidney disease status established within 6 months of plasma collection.

The researchers found that lower estimated glomerular filtration rate levels (indicative of kidney dysfunction) were associated with higher plasma concentrations of phosphorylated and unphosphorylated tau peptides measured simultaneously using the tau immunoprecipitation mass spectrometry assay.

However, the correlations with estimated glomerular filtration rate were nonsignificant for the pT217/T217 ratio in individuals with cognitive impairment and were significantly attenuated for pT217/T217 in cognitively unimpaired individuals and for pT181/T181 in both cognitively unimpaired and impaired individuals.

“Importantly, we demonstrate that there were no significant associations between chronic kidney disease and the pT217/T217 ratio and changes in plasma pT181/T181 associated with chronic kidney disease were small or nonsignificant,” the researchers noted.

“Our results indicate that by using p-tau/tau ratios we may be able to reduce the variability in plasma p-tau levels driven by impaired kidney function and consequently such ratios are more robust measures of brain p-tau pathology in individuals with both early- and later-stage Alzheimer’s disease,” they added.

The researchers believe this is likely true for the ratios of other related proteins – a view that is supported by findings of attenuated associations of chronic kidney disease with Abeta42/40, compared with Abeta42 and Abeta40 in the current study and in previous studies.
 

Important clinical implications

Reached for comment, Rebecca Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, noted that research continues to indicate that blood biomarkers have “promise for improving, and possibly even redefining, the clinical workup for Alzheimer’s disease.

“Many of the Alzheimer’s blood tests in development today have focused on core blood biomarkers associated with amyloid accumulation and tau tangle formation in the brain,” Dr. Edelmayer said.

“Before these tests can be used more broadly in the clinic, we need to understand all of the variables that may impact the results of various blood biomarkers, including differences that may be driven by race, ethnicity, sex, and underlying health conditions, such as chronic kidney disease.

“This study corroborates other research suggesting that some Alzheimer’s-associated markers can be affected by chronic kidney disease, but by using ratios of amyloid or tau markers, we may be able to minimize these differences in results caused by underlying disease,” Dr. Edelmayer said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said, “Using these ratios makes a lot of sense because the ratios wouldn’t change with kidney function. I think this is an important advance in clinical utilization of these tests.”

Dr. Fillit noted that older people often have declining kidney function, which can be easily measured by glomerular filtration rate. Changes in blood levels of these markers with declining kidney function are “not unexpected, but [it’s] important that it’s been demonstrated.

“As we go forward, maybe the future utilization of these tests will be not only recording the ratios but also reporting the ratios in the context of somebody’s glomerular filtration rate. You could imagine a scenario where when the test is done, it’s automatically done alongside of glomerular filtration rate,” Dr. Fillit said in an interview.

The study was supported by Coins for Alzheimer’s Research Trust, the Tracy Family Stable Isotope Labeling Quantitation Center, and the National Institute of Neurological Disorders and Stroke. Dr. Hansson has received support to his institution from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche; consultancy/speaker fees from Amylyx, Alzpath, Biogen, Cerveau, Fujirebio, Genentech, Novartis, Roche, and Siemens; and personal fees from Eli Lilly, Eisai, Bioarctic, and Biogen outside the submitted work. Dr. Edelmayer and Dr. Fillit have disclosed no relevant financial relationships.

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

New research provides more evidence that tau plasma biomarkers associated with Alzheimer’s disease can be skewed by chronic kidney disease and suggests that using ratios of these biomarkers can attenuate the skewed results.

In a cross-sectional study of adults with and those without cognitive impairment, chronic kidney disease was associated with increased plasma concentrations of phosphorylated tau (p-tau) 217 and 181.

However, there were no associations between chronic kidney disease and the ratio of p-tau217 to unphosphorylated tau 217 (pT217/T217), and the associations with p-tau181 to unphosphorylated tau 181 (pT181/T181) were attenuated in patients with cognitive impairment.

“These novel findings suggest that plasma measures of the phosphorylated to unphosphorylated tau ratios are more accurate than p-tau forms alone as they correlate less with individual difference in glomerular filtration rate or impaired kidney function,” reported an investigative team led by Oskar Hansson, MD, PhD, with Lund University in Sweden.

“Thus, to mitigate the effects of non-Alzheimer’s–related comorbidities like chronic kidney disease on the performance of plasma Alzheimer’s disease biomarkers, certain tau ratios, and specifically pT217/T217, should be considered for implementation in clinical practice and drug trials,” they added.

The study was published online in JAMA Neurology to coincide with a presentation at the International Conference on Alzheimer’s and Parkinson’s Diseases in Gothenburg, Sweden.


 

Skewed tau levels

Plasma biomarkers of amyloid-beta (Abeta) and tau pathologies, and in particular variants in p-tau217 and p-tau181, have shown promise for use in Alzheimer’s disease diagnosis and prognosis. However, previous reports have suggested that chronic kidney disease might influence plasma p-tau217 and p-tau181 concentrations, potentially decreasing their usefulness in the diagnostic workup of dementia.

Researchers investigated associations of chronic kidney disease with plasma ratios of p-tau217 and p-tau181 to the corresponding unphosphorylated peptides in Alzheimer’s disease.

The data came from 473 older adults, with and without cognitive impairment, from the Swedish BioFinder-2 study who had plasma tau assessments and chronic kidney disease status established within 6 months of plasma collection.

The researchers found that lower estimated glomerular filtration rate levels (indicative of kidney dysfunction) were associated with higher plasma concentrations of phosphorylated and unphosphorylated tau peptides measured simultaneously using the tau immunoprecipitation mass spectrometry assay.

However, the correlations with estimated glomerular filtration rate were nonsignificant for the pT217/T217 ratio in individuals with cognitive impairment and were significantly attenuated for pT217/T217 in cognitively unimpaired individuals and for pT181/T181 in both cognitively unimpaired and impaired individuals.

“Importantly, we demonstrate that there were no significant associations between chronic kidney disease and the pT217/T217 ratio and changes in plasma pT181/T181 associated with chronic kidney disease were small or nonsignificant,” the researchers noted.

“Our results indicate that by using p-tau/tau ratios we may be able to reduce the variability in plasma p-tau levels driven by impaired kidney function and consequently such ratios are more robust measures of brain p-tau pathology in individuals with both early- and later-stage Alzheimer’s disease,” they added.

The researchers believe this is likely true for the ratios of other related proteins – a view that is supported by findings of attenuated associations of chronic kidney disease with Abeta42/40, compared with Abeta42 and Abeta40 in the current study and in previous studies.
 

Important clinical implications

Reached for comment, Rebecca Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, noted that research continues to indicate that blood biomarkers have “promise for improving, and possibly even redefining, the clinical workup for Alzheimer’s disease.

“Many of the Alzheimer’s blood tests in development today have focused on core blood biomarkers associated with amyloid accumulation and tau tangle formation in the brain,” Dr. Edelmayer said.

“Before these tests can be used more broadly in the clinic, we need to understand all of the variables that may impact the results of various blood biomarkers, including differences that may be driven by race, ethnicity, sex, and underlying health conditions, such as chronic kidney disease.

“This study corroborates other research suggesting that some Alzheimer’s-associated markers can be affected by chronic kidney disease, but by using ratios of amyloid or tau markers, we may be able to minimize these differences in results caused by underlying disease,” Dr. Edelmayer said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said, “Using these ratios makes a lot of sense because the ratios wouldn’t change with kidney function. I think this is an important advance in clinical utilization of these tests.”

Dr. Fillit noted that older people often have declining kidney function, which can be easily measured by glomerular filtration rate. Changes in blood levels of these markers with declining kidney function are “not unexpected, but [it’s] important that it’s been demonstrated.

“As we go forward, maybe the future utilization of these tests will be not only recording the ratios but also reporting the ratios in the context of somebody’s glomerular filtration rate. You could imagine a scenario where when the test is done, it’s automatically done alongside of glomerular filtration rate,” Dr. Fillit said in an interview.

The study was supported by Coins for Alzheimer’s Research Trust, the Tracy Family Stable Isotope Labeling Quantitation Center, and the National Institute of Neurological Disorders and Stroke. Dr. Hansson has received support to his institution from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche; consultancy/speaker fees from Amylyx, Alzpath, Biogen, Cerveau, Fujirebio, Genentech, Novartis, Roche, and Siemens; and personal fees from Eli Lilly, Eisai, Bioarctic, and Biogen outside the submitted work. Dr. Edelmayer and Dr. Fillit have disclosed no relevant financial relationships.

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

A mindfulness-based cognitive therapy self-help (MBCT-SH) intervention in which patients were supported by a trained practitioner led to better clinical outcomes at lower cost than practitioner-supported cognitive-behavioral therapy self-help (CBT-SH), new research shows.

The findings suggest that “offering practitioner-supported MBCT-SH as an intervention for mild to moderate depression would improve outcomes and save money compared with practitioner-supported CBT-SH,” noted the investigators, led by Clara Strauss, PhD, DClinPsy, with the University of Sussex School of Psychology in England.

Practitioner-supported CBT-SH is recommended in U.K. national treatment guidelines for mild to moderate depression. However, some patients’ conditions don’t respond, and dropout rates are high.

The Low-Intensity Guided Help Through Mindfulness (LIGHTMind) trial tested practitioner-supported MBCT-SH as an alternative.

The findings have “important implications” for the more than 100,000 people currently offered CBT-SH for depression in the Improving Access to Psychological Therapies (IAPT) program each year and in publicly funded services elsewhere, the researchers noted.

If translated into routine practice, “this would see many more people recovering from depression while costing health services less money,” they added.

The study was published online in JAMA Psychiatry .
 

Practice changing?

The trial included 410 adults (mean age, 32 years; 62% women) with mild to moderate depression who were recruited from 10 publicly funded psychological therapy services in England as part of the IAPT program.

Participants were given one of two established self-help workbooks – The Mindful Way Workbook: An 8-Week Program to Free Yourself from Depression and Emotional Distress, written by the pioneers of MBCT, or Overcoming Depression and Low Mood, 3rd Edition: A Five Areas Approach, which is a CBT-SH program widely used in IAPT.

Use of the self-help books was supported by six structured phone or in-person sessions with a trained psychological well-being practitioner.

The primary outcome was depression symptom severity at 16 weeks, which was determined on the basis of Patient Health Questionnaire 9 (PHQ-9) score.

At 16 weeks following randomization, MBCT-SH led to significantly greater reductions in depression symptom severity compared with CBT-SH (mean PHQ-9 score, 7.2 vs. 8.6; between-group difference, 1.5 points; P = .009; d = −0.36).

MBCT-SH also had superior effects on anxiety symptom severity at 16 weeks.

At the 42-week follow-up, between-group effects on depression and anxiety symptom severity remained in the hypothesized direction but were nonsignificant.

This could be due in part by the greater postintervention psychological therapy accessed by participants in the CBT-SH group, the investigators noted.

Practitioner-supported MBCT-SH was more cost-effective than supported CBT-SH.

On average, the CBT-SH intervention cost health services £526 ($631) more per participant than the MBCT-SH intervention over the 42-week follow-up. The probability of MBCT-SH being cost-effective compared with CBT-SH exceeded 95%, the researchers noted.
 

Useful model for the United States

Commenting for this news organization, Zindel Segal, PhD, professor of psychology, University of Toronto, Scarborough, cautioned against making too much of the differences between the groups, because CBT-SH “trended positive and had a pretty healthy effect size, it just never reached significance.

“I wouldn’t say mindfulness drastically outperformed cognitive therapy. But cognitive therapy is a robust treatment in its own right, and so doing a little bit better is significant,” Dr. Segal said.

He also noted that, appropriately, the trial enrolled adults who were experiencing moderate depression and were not acutely ill. “That’s one of the rationales for self-help compared to providing patients with a more resource-intensive group treatment.

“If you look at the needs of people with moderate depression, what you find is that for cognitive therapy to work, negative thoughts and feelings need to be pervasive in order to make use of the techniques,” Dr. Segal explained.

“With mindfulness, you don’t need any to have constant negative thoughts or feelings. Anything that arises in your experience serves as grist for mill in terms of concentration and focus,” Dr. Segal said.

He also noted that mindfulness-based intervention is “more optimized” for people who are experiencing some measure of recovery or remission.

“It’s well suited for that, as it trends towards the wellness spectrum. But for people who might have greater levels of acuity or severity, cognitive-behavioral therapy might be indicated,” said Dr. Segal.

He also said the U.K. study findings are relevant to U.S. patients with depression.

“While it’s not disseminated in the same way through any kind of national program, the self-help books that are used are widely available, and the support that people were offered, either in person, telephone, or email, could be easily delivered. This would be a very useful model,” Dr. Segal said.

The LIGHTMind trial was funded by the National Institute for Health and Care Research and the Brighton and Sussex Clinical Trials Unit. Dr. Strauss has received grants from Headspace, is research lead for Sussex Mindfulness Centre, and has been chief investigator on National Institute for Health and Care Research. Dr. Segal is one of the authors of the MBCT-SH workbooks used in the study.
 

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

A mindfulness-based cognitive therapy self-help (MBCT-SH) intervention in which patients were supported by a trained practitioner led to better clinical outcomes at lower cost than practitioner-supported cognitive-behavioral therapy self-help (CBT-SH), new research shows.

The findings suggest that “offering practitioner-supported MBCT-SH as an intervention for mild to moderate depression would improve outcomes and save money compared with practitioner-supported CBT-SH,” noted the investigators, led by Clara Strauss, PhD, DClinPsy, with the University of Sussex School of Psychology in England.

Practitioner-supported CBT-SH is recommended in U.K. national treatment guidelines for mild to moderate depression. However, some patients’ conditions don’t respond, and dropout rates are high.

The Low-Intensity Guided Help Through Mindfulness (LIGHTMind) trial tested practitioner-supported MBCT-SH as an alternative.

The findings have “important implications” for the more than 100,000 people currently offered CBT-SH for depression in the Improving Access to Psychological Therapies (IAPT) program each year and in publicly funded services elsewhere, the researchers noted.

If translated into routine practice, “this would see many more people recovering from depression while costing health services less money,” they added.

The study was published online in JAMA Psychiatry .
 

Practice changing?

The trial included 410 adults (mean age, 32 years; 62% women) with mild to moderate depression who were recruited from 10 publicly funded psychological therapy services in England as part of the IAPT program.

Participants were given one of two established self-help workbooks – The Mindful Way Workbook: An 8-Week Program to Free Yourself from Depression and Emotional Distress, written by the pioneers of MBCT, or Overcoming Depression and Low Mood, 3rd Edition: A Five Areas Approach, which is a CBT-SH program widely used in IAPT.

Use of the self-help books was supported by six structured phone or in-person sessions with a trained psychological well-being practitioner.

The primary outcome was depression symptom severity at 16 weeks, which was determined on the basis of Patient Health Questionnaire 9 (PHQ-9) score.

At 16 weeks following randomization, MBCT-SH led to significantly greater reductions in depression symptom severity compared with CBT-SH (mean PHQ-9 score, 7.2 vs. 8.6; between-group difference, 1.5 points; P = .009; d = −0.36).

MBCT-SH also had superior effects on anxiety symptom severity at 16 weeks.

At the 42-week follow-up, between-group effects on depression and anxiety symptom severity remained in the hypothesized direction but were nonsignificant.

This could be due in part by the greater postintervention psychological therapy accessed by participants in the CBT-SH group, the investigators noted.

Practitioner-supported MBCT-SH was more cost-effective than supported CBT-SH.

On average, the CBT-SH intervention cost health services £526 ($631) more per participant than the MBCT-SH intervention over the 42-week follow-up. The probability of MBCT-SH being cost-effective compared with CBT-SH exceeded 95%, the researchers noted.
 

Useful model for the United States

Commenting for this news organization, Zindel Segal, PhD, professor of psychology, University of Toronto, Scarborough, cautioned against making too much of the differences between the groups, because CBT-SH “trended positive and had a pretty healthy effect size, it just never reached significance.

“I wouldn’t say mindfulness drastically outperformed cognitive therapy. But cognitive therapy is a robust treatment in its own right, and so doing a little bit better is significant,” Dr. Segal said.

He also noted that, appropriately, the trial enrolled adults who were experiencing moderate depression and were not acutely ill. “That’s one of the rationales for self-help compared to providing patients with a more resource-intensive group treatment.

“If you look at the needs of people with moderate depression, what you find is that for cognitive therapy to work, negative thoughts and feelings need to be pervasive in order to make use of the techniques,” Dr. Segal explained.

“With mindfulness, you don’t need any to have constant negative thoughts or feelings. Anything that arises in your experience serves as grist for mill in terms of concentration and focus,” Dr. Segal said.

He also noted that mindfulness-based intervention is “more optimized” for people who are experiencing some measure of recovery or remission.

“It’s well suited for that, as it trends towards the wellness spectrum. But for people who might have greater levels of acuity or severity, cognitive-behavioral therapy might be indicated,” said Dr. Segal.

He also said the U.K. study findings are relevant to U.S. patients with depression.

“While it’s not disseminated in the same way through any kind of national program, the self-help books that are used are widely available, and the support that people were offered, either in person, telephone, or email, could be easily delivered. This would be a very useful model,” Dr. Segal said.

The LIGHTMind trial was funded by the National Institute for Health and Care Research and the Brighton and Sussex Clinical Trials Unit. Dr. Strauss has received grants from Headspace, is research lead for Sussex Mindfulness Centre, and has been chief investigator on National Institute for Health and Care Research. Dr. Segal is one of the authors of the MBCT-SH workbooks used in the study.
 

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

A mindfulness-based cognitive therapy self-help (MBCT-SH) intervention in which patients were supported by a trained practitioner led to better clinical outcomes at lower cost than practitioner-supported cognitive-behavioral therapy self-help (CBT-SH), new research shows.

The findings suggest that “offering practitioner-supported MBCT-SH as an intervention for mild to moderate depression would improve outcomes and save money compared with practitioner-supported CBT-SH,” noted the investigators, led by Clara Strauss, PhD, DClinPsy, with the University of Sussex School of Psychology in England.

Practitioner-supported CBT-SH is recommended in U.K. national treatment guidelines for mild to moderate depression. However, some patients’ conditions don’t respond, and dropout rates are high.

The Low-Intensity Guided Help Through Mindfulness (LIGHTMind) trial tested practitioner-supported MBCT-SH as an alternative.

The findings have “important implications” for the more than 100,000 people currently offered CBT-SH for depression in the Improving Access to Psychological Therapies (IAPT) program each year and in publicly funded services elsewhere, the researchers noted.

If translated into routine practice, “this would see many more people recovering from depression while costing health services less money,” they added.

The study was published online in JAMA Psychiatry .
 

Practice changing?

The trial included 410 adults (mean age, 32 years; 62% women) with mild to moderate depression who were recruited from 10 publicly funded psychological therapy services in England as part of the IAPT program.

Participants were given one of two established self-help workbooks – The Mindful Way Workbook: An 8-Week Program to Free Yourself from Depression and Emotional Distress, written by the pioneers of MBCT, or Overcoming Depression and Low Mood, 3rd Edition: A Five Areas Approach, which is a CBT-SH program widely used in IAPT.

Use of the self-help books was supported by six structured phone or in-person sessions with a trained psychological well-being practitioner.

The primary outcome was depression symptom severity at 16 weeks, which was determined on the basis of Patient Health Questionnaire 9 (PHQ-9) score.

At 16 weeks following randomization, MBCT-SH led to significantly greater reductions in depression symptom severity compared with CBT-SH (mean PHQ-9 score, 7.2 vs. 8.6; between-group difference, 1.5 points; P = .009; d = −0.36).

MBCT-SH also had superior effects on anxiety symptom severity at 16 weeks.

At the 42-week follow-up, between-group effects on depression and anxiety symptom severity remained in the hypothesized direction but were nonsignificant.

This could be due in part by the greater postintervention psychological therapy accessed by participants in the CBT-SH group, the investigators noted.

Practitioner-supported MBCT-SH was more cost-effective than supported CBT-SH.

On average, the CBT-SH intervention cost health services £526 ($631) more per participant than the MBCT-SH intervention over the 42-week follow-up. The probability of MBCT-SH being cost-effective compared with CBT-SH exceeded 95%, the researchers noted.
 

Useful model for the United States

Commenting for this news organization, Zindel Segal, PhD, professor of psychology, University of Toronto, Scarborough, cautioned against making too much of the differences between the groups, because CBT-SH “trended positive and had a pretty healthy effect size, it just never reached significance.

“I wouldn’t say mindfulness drastically outperformed cognitive therapy. But cognitive therapy is a robust treatment in its own right, and so doing a little bit better is significant,” Dr. Segal said.

He also noted that, appropriately, the trial enrolled adults who were experiencing moderate depression and were not acutely ill. “That’s one of the rationales for self-help compared to providing patients with a more resource-intensive group treatment.

“If you look at the needs of people with moderate depression, what you find is that for cognitive therapy to work, negative thoughts and feelings need to be pervasive in order to make use of the techniques,” Dr. Segal explained.

“With mindfulness, you don’t need any to have constant negative thoughts or feelings. Anything that arises in your experience serves as grist for mill in terms of concentration and focus,” Dr. Segal said.

He also noted that mindfulness-based intervention is “more optimized” for people who are experiencing some measure of recovery or remission.

“It’s well suited for that, as it trends towards the wellness spectrum. But for people who might have greater levels of acuity or severity, cognitive-behavioral therapy might be indicated,” said Dr. Segal.

He also said the U.K. study findings are relevant to U.S. patients with depression.

“While it’s not disseminated in the same way through any kind of national program, the self-help books that are used are widely available, and the support that people were offered, either in person, telephone, or email, could be easily delivered. This would be a very useful model,” Dr. Segal said.

The LIGHTMind trial was funded by the National Institute for Health and Care Research and the Brighton and Sussex Clinical Trials Unit. Dr. Strauss has received grants from Headspace, is research lead for Sussex Mindfulness Centre, and has been chief investigator on National Institute for Health and Care Research. Dr. Segal is one of the authors of the MBCT-SH workbooks used in the study.
 

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

The youngest patient with cannabis-induced psychosis (CIP) whom Karen Randall, DO, has treated was a 7-year-old boy. She remembers the screaming, the yelling, the uncontrollable rage.

Dr. Randall is an emergency medicine physician at Southern Colorado Emergency Medicine Associates, a group practice in Pueblo, Colo. She treats youth for cannabis-related medical problems in the emergency department an average of two or three times per shift, she said.

Colorado legalized the recreational use of cannabis for adults older than 21 in 2012. Since then, Dr. Randall said, she has noticed an uptick in cannabis use among youth, as well as an increase in CIP, a syndrome that can be indistinguishable from other psychiatric disorders such as schizophrenia in the emergency department. But the two conditions require different approaches to care.

“You can’t differentiate unless you know the patient,” Dr. Randall said in an interview.

In 2019, 37% of high school students in the United States reported ever using marijuana, and 22% reported use in the past 30 days. Rates remained steady in 2020 following increases in 2018 and 2019, according to the Centers for Disease Control and Prevention.

The CDC also found that 8% of 8th graders, 19% of 10th graders, and 22% of 12th graders reported vaping marijuana in the past year.

Clinicians in states where recreational marijuana has been legalized say they have noticed an increase in young patients with psychiatric problems – especially after consumption of cannabis products in high doses. But CIP can be tricky to distinguish from psychoses of other causes, such as schizophrenia or bipolar disorder, which often begin to present in adolescence.
 

How to differentiate

CIP is characterized by delusions and hallucinations and sometimes anxiety, disorganized thoughts, paranoia, dissociation, and changes in mood and behavior. Symptoms typically last for a couple hours and do not require specific treatment, although they can persist, depending on a patient’s tolerance and the dose of tetrahydrocannabinol (THC) they have consumed. Research suggests that the higher the dose and concentration of the drug consumed, the more likely a person will develop symptoms of psychosis.

Diagnosis requires gathering information on previous bipolar disorder or schizophrenia diagnosis, prescriptions for mental illness indications, whether there is a family history of mental illness, and whether the patient recently started using marijuana. In some cases, marijuana use might exacerbate or unmask mental illness.

If symptoms of CIP resolve, and usually they do, clinicians can recommend that patients abstain from cannabis going forward, and psychosis would not need further treatment, according to Divya Singh, MD, a psychiatrist at Banner Behavioral Health Hospital in Scottsdale, Ariz., where recreational cannabis became legal in 2020.

“When I have limited information, especially in the first couple of days, I err on the side of safety,” Dr. Singh said.

Psychosis is the combination of symptoms, including delusions, hallucinations, and disorganized behavior, but it is not a disorder in itself. Rather, it is the primary symptom of schizophrenia and other chronic psychiatric illnesses.

Schizophrenia can be diagnosed only after a patient presents with signs of disturbance for at least 6 months, according to guidelines in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Dr. Singh said a diagnosis of schizophrenia cannot be made in a one-off interaction.

If the patient is younger than 24 years and has no family history of mental illness, a full recovery is likely if the patient abstains from marijuana, he said. But if the patient does have a family history, “the chances of them having a full-blown mental illness is very high,” Dr. Singh said.

If a patient reports that he or she has recently started using marijuana and was previously diagnosed with bipolar disorder or schizophrenia, Dr. Singh said he generally prescribes medications such as lithium or quetiapine and refers the patient to services such as cognitive-behavioral therapy. He also advises against continuing use of cannabis.

“Cannabis can result in people requiring a higher dose of medication than they took before,” Dr. Singh said. “If they were stable on 600 mg of lithium before, they might need more and may never be able to lower the dose in some cases, even after the acute episode.”
 

The science of cannabis

As of March 2023, 21 states and the District of Columbia permit the recreational use of marijuana, according to the Congressional Research Service. Thirty-seven states and the District of Columbia allow medicinal use of marijuana, and 10 states allow “limited access to medical cannabis,” defined as low-THC cannabis or cannabidiol (CBD) oil.

THC is the main psychoactive compound in cannabis. It creates a high feeling after binding with receptors in the brain that control pain and mood. CBD is another chemical found in cannabis, but it does not create a high.

Some research suggests cannabinoids may help reduce anxiety, reduce inflammation, relieve pain, control nausea, reduce cancer cells, slow the growth of tumor cells, relax tight muscles, and stimulate appetite.

The drug also carries risks, according to Mayo Clinic. Use of marijuana is linked to mental health problems in teens and adults, such as depression, social anxiety, and temporary psychosis, and long-lasting mental disorders, such as schizophrenia.

In the worst cases, CIP can persist for weeks or months – long after a negative drug test – and sometimes does not subside at all, according to Ken Finn, MD, president and founder of Springs Rehabilitation, PC, a pain medicine practice in Colorado Springs, Colo.

Dr. Finn, the co–vice president of the International Academy on the Science and Impact of Cannabis, which opposes making the drug more accessible, said educating health care providers is an urgent need.

Studies are mixed on whether the legalization of cannabis has led to more cases of CIP.

A 2021 study found that experiences of psychosis among users of cannabis jumped 2.5-fold between 2001 and 2013. But a study published earlier this year of more than 63 million medical claims from 2003 to 2017 found no statistically significant difference in rates of psychosis-related diagnoses or prescribed antipsychotics in states that have legalized medical or recreational cannabis compared with states where cannabis is still illegal. However, a secondary analysis did find that rates of psychosis-related diagnoses increased significantly among men, people aged 55-64 years, and Asian adults in states where recreational marijuana has been legalized.

Complicating matters, researchers say, is the question of causality. Cannabis may exacerbate or trigger psychosis, but people with an underlying psychological illness may also be more likely to use cannabis.

Dr. Finn said clinicians in Colorado and other states with legalization laws are seeing more patients with CIP. As more states consider legalizing recreational marijuana, he expects the data will reflect what doctors experience on the ground.

Cannabis-induced “psychosis is complicated and likely underdiagnosed,” Dr. Finn said.
 

Talking to teens

Clinicians outside the emergency department can play a role in aiding young people at risk for CIP. Primary care physicians, for instance, might explain to young patients that the brain only becomes fully developed at roughly age 26, after which the long-term health consequences of using cannabis become less likely. According to the CDC, using cannabis before age 18 can change how the brain builds connections and can impair attention, memory, and learning.

Dr. Singh takes a harm reduction approach when he engages with a patient who is forthcoming about substance use.

“If I see an 18-year-old, I tell them to abstain,” he said. “I tell them if they are ever going to use it, to use it after 26.”

Clinicians also should understand dosages to provide the optimal guidance to their patients who use cannabis.

“People often have no idea how much cannabis they are taking,” especially when using vape cartridges, Dr. Singh said. “If you don’t know, you can’t tell patients about the harms – and if you tell them the wrong information, they will write you off.”

Dr. Singh said he advises his patients to avoid using cannabis vapes or dabbing pens. Both can contain much higher levels of THC than dried flower or edible forms of the drug. He also says patients should stick with low concentrations and use products that contain CBD, which some studies have shown has a protective effect against CIP, although other studies have found that CBD can induce anxiety.

He also tells patients to buy from legal dispensaries and to avoid buying street products that may have methamphetamine or fentanyl mixed in.

Despite the risks, Dr. Singh said legalization can reduce the stigma associated with cannabis use and may prompt patients to be honest with their clinicians. Dr. Singh recalled a 28-year-old patient who was using cannabis to alleviate her arthritic pain. She also was taking a transplant medication, which carried potential side effects of delirium, generalized anxiety disorder, and hallucinosis. After doubling her THC dose, the patient experienced severe anxiety and paranoia.

Dr. Singh’s patient paid him a visit and asked for help. Dr. Singh told her to reduce the dose and to keep track of how she felt. If she continued to feel anxious and paranoid, he recommended that she switch to CBD instead.

“I think education and knowledge is liberating,” Dr. Singh said. “Legalization and frank conversations help people understand how to use a product – and right now, I think that’s lacking.”
 

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

The youngest patient with cannabis-induced psychosis (CIP) whom Karen Randall, DO, has treated was a 7-year-old boy. She remembers the screaming, the yelling, the uncontrollable rage.

Dr. Randall is an emergency medicine physician at Southern Colorado Emergency Medicine Associates, a group practice in Pueblo, Colo. She treats youth for cannabis-related medical problems in the emergency department an average of two or three times per shift, she said.

Colorado legalized the recreational use of cannabis for adults older than 21 in 2012. Since then, Dr. Randall said, she has noticed an uptick in cannabis use among youth, as well as an increase in CIP, a syndrome that can be indistinguishable from other psychiatric disorders such as schizophrenia in the emergency department. But the two conditions require different approaches to care.

“You can’t differentiate unless you know the patient,” Dr. Randall said in an interview.

In 2019, 37% of high school students in the United States reported ever using marijuana, and 22% reported use in the past 30 days. Rates remained steady in 2020 following increases in 2018 and 2019, according to the Centers for Disease Control and Prevention.

The CDC also found that 8% of 8th graders, 19% of 10th graders, and 22% of 12th graders reported vaping marijuana in the past year.

Clinicians in states where recreational marijuana has been legalized say they have noticed an increase in young patients with psychiatric problems – especially after consumption of cannabis products in high doses. But CIP can be tricky to distinguish from psychoses of other causes, such as schizophrenia or bipolar disorder, which often begin to present in adolescence.
 

How to differentiate

CIP is characterized by delusions and hallucinations and sometimes anxiety, disorganized thoughts, paranoia, dissociation, and changes in mood and behavior. Symptoms typically last for a couple hours and do not require specific treatment, although they can persist, depending on a patient’s tolerance and the dose of tetrahydrocannabinol (THC) they have consumed. Research suggests that the higher the dose and concentration of the drug consumed, the more likely a person will develop symptoms of psychosis.

Diagnosis requires gathering information on previous bipolar disorder or schizophrenia diagnosis, prescriptions for mental illness indications, whether there is a family history of mental illness, and whether the patient recently started using marijuana. In some cases, marijuana use might exacerbate or unmask mental illness.

If symptoms of CIP resolve, and usually they do, clinicians can recommend that patients abstain from cannabis going forward, and psychosis would not need further treatment, according to Divya Singh, MD, a psychiatrist at Banner Behavioral Health Hospital in Scottsdale, Ariz., where recreational cannabis became legal in 2020.

“When I have limited information, especially in the first couple of days, I err on the side of safety,” Dr. Singh said.

Psychosis is the combination of symptoms, including delusions, hallucinations, and disorganized behavior, but it is not a disorder in itself. Rather, it is the primary symptom of schizophrenia and other chronic psychiatric illnesses.

Schizophrenia can be diagnosed only after a patient presents with signs of disturbance for at least 6 months, according to guidelines in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Dr. Singh said a diagnosis of schizophrenia cannot be made in a one-off interaction.

If the patient is younger than 24 years and has no family history of mental illness, a full recovery is likely if the patient abstains from marijuana, he said. But if the patient does have a family history, “the chances of them having a full-blown mental illness is very high,” Dr. Singh said.

If a patient reports that he or she has recently started using marijuana and was previously diagnosed with bipolar disorder or schizophrenia, Dr. Singh said he generally prescribes medications such as lithium or quetiapine and refers the patient to services such as cognitive-behavioral therapy. He also advises against continuing use of cannabis.

“Cannabis can result in people requiring a higher dose of medication than they took before,” Dr. Singh said. “If they were stable on 600 mg of lithium before, they might need more and may never be able to lower the dose in some cases, even after the acute episode.”
 

The science of cannabis

As of March 2023, 21 states and the District of Columbia permit the recreational use of marijuana, according to the Congressional Research Service. Thirty-seven states and the District of Columbia allow medicinal use of marijuana, and 10 states allow “limited access to medical cannabis,” defined as low-THC cannabis or cannabidiol (CBD) oil.

THC is the main psychoactive compound in cannabis. It creates a high feeling after binding with receptors in the brain that control pain and mood. CBD is another chemical found in cannabis, but it does not create a high.

Some research suggests cannabinoids may help reduce anxiety, reduce inflammation, relieve pain, control nausea, reduce cancer cells, slow the growth of tumor cells, relax tight muscles, and stimulate appetite.

The drug also carries risks, according to Mayo Clinic. Use of marijuana is linked to mental health problems in teens and adults, such as depression, social anxiety, and temporary psychosis, and long-lasting mental disorders, such as schizophrenia.

In the worst cases, CIP can persist for weeks or months – long after a negative drug test – and sometimes does not subside at all, according to Ken Finn, MD, president and founder of Springs Rehabilitation, PC, a pain medicine practice in Colorado Springs, Colo.

Dr. Finn, the co–vice president of the International Academy on the Science and Impact of Cannabis, which opposes making the drug more accessible, said educating health care providers is an urgent need.

Studies are mixed on whether the legalization of cannabis has led to more cases of CIP.

A 2021 study found that experiences of psychosis among users of cannabis jumped 2.5-fold between 2001 and 2013. But a study published earlier this year of more than 63 million medical claims from 2003 to 2017 found no statistically significant difference in rates of psychosis-related diagnoses or prescribed antipsychotics in states that have legalized medical or recreational cannabis compared with states where cannabis is still illegal. However, a secondary analysis did find that rates of psychosis-related diagnoses increased significantly among men, people aged 55-64 years, and Asian adults in states where recreational marijuana has been legalized.

Complicating matters, researchers say, is the question of causality. Cannabis may exacerbate or trigger psychosis, but people with an underlying psychological illness may also be more likely to use cannabis.

Dr. Finn said clinicians in Colorado and other states with legalization laws are seeing more patients with CIP. As more states consider legalizing recreational marijuana, he expects the data will reflect what doctors experience on the ground.

Cannabis-induced “psychosis is complicated and likely underdiagnosed,” Dr. Finn said.
 

Talking to teens

Clinicians outside the emergency department can play a role in aiding young people at risk for CIP. Primary care physicians, for instance, might explain to young patients that the brain only becomes fully developed at roughly age 26, after which the long-term health consequences of using cannabis become less likely. According to the CDC, using cannabis before age 18 can change how the brain builds connections and can impair attention, memory, and learning.

Dr. Singh takes a harm reduction approach when he engages with a patient who is forthcoming about substance use.

“If I see an 18-year-old, I tell them to abstain,” he said. “I tell them if they are ever going to use it, to use it after 26.”

Clinicians also should understand dosages to provide the optimal guidance to their patients who use cannabis.

“People often have no idea how much cannabis they are taking,” especially when using vape cartridges, Dr. Singh said. “If you don’t know, you can’t tell patients about the harms – and if you tell them the wrong information, they will write you off.”

Dr. Singh said he advises his patients to avoid using cannabis vapes or dabbing pens. Both can contain much higher levels of THC than dried flower or edible forms of the drug. He also says patients should stick with low concentrations and use products that contain CBD, which some studies have shown has a protective effect against CIP, although other studies have found that CBD can induce anxiety.

He also tells patients to buy from legal dispensaries and to avoid buying street products that may have methamphetamine or fentanyl mixed in.

Despite the risks, Dr. Singh said legalization can reduce the stigma associated with cannabis use and may prompt patients to be honest with their clinicians. Dr. Singh recalled a 28-year-old patient who was using cannabis to alleviate her arthritic pain. She also was taking a transplant medication, which carried potential side effects of delirium, generalized anxiety disorder, and hallucinosis. After doubling her THC dose, the patient experienced severe anxiety and paranoia.

Dr. Singh’s patient paid him a visit and asked for help. Dr. Singh told her to reduce the dose and to keep track of how she felt. If she continued to feel anxious and paranoid, he recommended that she switch to CBD instead.

“I think education and knowledge is liberating,” Dr. Singh said. “Legalization and frank conversations help people understand how to use a product – and right now, I think that’s lacking.”
 

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

The youngest patient with cannabis-induced psychosis (CIP) whom Karen Randall, DO, has treated was a 7-year-old boy. She remembers the screaming, the yelling, the uncontrollable rage.

Dr. Randall is an emergency medicine physician at Southern Colorado Emergency Medicine Associates, a group practice in Pueblo, Colo. She treats youth for cannabis-related medical problems in the emergency department an average of two or three times per shift, she said.

Colorado legalized the recreational use of cannabis for adults older than 21 in 2012. Since then, Dr. Randall said, she has noticed an uptick in cannabis use among youth, as well as an increase in CIP, a syndrome that can be indistinguishable from other psychiatric disorders such as schizophrenia in the emergency department. But the two conditions require different approaches to care.

“You can’t differentiate unless you know the patient,” Dr. Randall said in an interview.

In 2019, 37% of high school students in the United States reported ever using marijuana, and 22% reported use in the past 30 days. Rates remained steady in 2020 following increases in 2018 and 2019, according to the Centers for Disease Control and Prevention.

The CDC also found that 8% of 8th graders, 19% of 10th graders, and 22% of 12th graders reported vaping marijuana in the past year.

Clinicians in states where recreational marijuana has been legalized say they have noticed an increase in young patients with psychiatric problems – especially after consumption of cannabis products in high doses. But CIP can be tricky to distinguish from psychoses of other causes, such as schizophrenia or bipolar disorder, which often begin to present in adolescence.
 

How to differentiate

CIP is characterized by delusions and hallucinations and sometimes anxiety, disorganized thoughts, paranoia, dissociation, and changes in mood and behavior. Symptoms typically last for a couple hours and do not require specific treatment, although they can persist, depending on a patient’s tolerance and the dose of tetrahydrocannabinol (THC) they have consumed. Research suggests that the higher the dose and concentration of the drug consumed, the more likely a person will develop symptoms of psychosis.

Diagnosis requires gathering information on previous bipolar disorder or schizophrenia diagnosis, prescriptions for mental illness indications, whether there is a family history of mental illness, and whether the patient recently started using marijuana. In some cases, marijuana use might exacerbate or unmask mental illness.

If symptoms of CIP resolve, and usually they do, clinicians can recommend that patients abstain from cannabis going forward, and psychosis would not need further treatment, according to Divya Singh, MD, a psychiatrist at Banner Behavioral Health Hospital in Scottsdale, Ariz., where recreational cannabis became legal in 2020.

“When I have limited information, especially in the first couple of days, I err on the side of safety,” Dr. Singh said.

Psychosis is the combination of symptoms, including delusions, hallucinations, and disorganized behavior, but it is not a disorder in itself. Rather, it is the primary symptom of schizophrenia and other chronic psychiatric illnesses.

Schizophrenia can be diagnosed only after a patient presents with signs of disturbance for at least 6 months, according to guidelines in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Dr. Singh said a diagnosis of schizophrenia cannot be made in a one-off interaction.

If the patient is younger than 24 years and has no family history of mental illness, a full recovery is likely if the patient abstains from marijuana, he said. But if the patient does have a family history, “the chances of them having a full-blown mental illness is very high,” Dr. Singh said.

If a patient reports that he or she has recently started using marijuana and was previously diagnosed with bipolar disorder or schizophrenia, Dr. Singh said he generally prescribes medications such as lithium or quetiapine and refers the patient to services such as cognitive-behavioral therapy. He also advises against continuing use of cannabis.

“Cannabis can result in people requiring a higher dose of medication than they took before,” Dr. Singh said. “If they were stable on 600 mg of lithium before, they might need more and may never be able to lower the dose in some cases, even after the acute episode.”
 

The science of cannabis

As of March 2023, 21 states and the District of Columbia permit the recreational use of marijuana, according to the Congressional Research Service. Thirty-seven states and the District of Columbia allow medicinal use of marijuana, and 10 states allow “limited access to medical cannabis,” defined as low-THC cannabis or cannabidiol (CBD) oil.

THC is the main psychoactive compound in cannabis. It creates a high feeling after binding with receptors in the brain that control pain and mood. CBD is another chemical found in cannabis, but it does not create a high.

Some research suggests cannabinoids may help reduce anxiety, reduce inflammation, relieve pain, control nausea, reduce cancer cells, slow the growth of tumor cells, relax tight muscles, and stimulate appetite.

The drug also carries risks, according to Mayo Clinic. Use of marijuana is linked to mental health problems in teens and adults, such as depression, social anxiety, and temporary psychosis, and long-lasting mental disorders, such as schizophrenia.

In the worst cases, CIP can persist for weeks or months – long after a negative drug test – and sometimes does not subside at all, according to Ken Finn, MD, president and founder of Springs Rehabilitation, PC, a pain medicine practice in Colorado Springs, Colo.

Dr. Finn, the co–vice president of the International Academy on the Science and Impact of Cannabis, which opposes making the drug more accessible, said educating health care providers is an urgent need.

Studies are mixed on whether the legalization of cannabis has led to more cases of CIP.

A 2021 study found that experiences of psychosis among users of cannabis jumped 2.5-fold between 2001 and 2013. But a study published earlier this year of more than 63 million medical claims from 2003 to 2017 found no statistically significant difference in rates of psychosis-related diagnoses or prescribed antipsychotics in states that have legalized medical or recreational cannabis compared with states where cannabis is still illegal. However, a secondary analysis did find that rates of psychosis-related diagnoses increased significantly among men, people aged 55-64 years, and Asian adults in states where recreational marijuana has been legalized.

Complicating matters, researchers say, is the question of causality. Cannabis may exacerbate or trigger psychosis, but people with an underlying psychological illness may also be more likely to use cannabis.

Dr. Finn said clinicians in Colorado and other states with legalization laws are seeing more patients with CIP. As more states consider legalizing recreational marijuana, he expects the data will reflect what doctors experience on the ground.

Cannabis-induced “psychosis is complicated and likely underdiagnosed,” Dr. Finn said.
 

Talking to teens

Clinicians outside the emergency department can play a role in aiding young people at risk for CIP. Primary care physicians, for instance, might explain to young patients that the brain only becomes fully developed at roughly age 26, after which the long-term health consequences of using cannabis become less likely. According to the CDC, using cannabis before age 18 can change how the brain builds connections and can impair attention, memory, and learning.

Dr. Singh takes a harm reduction approach when he engages with a patient who is forthcoming about substance use.

“If I see an 18-year-old, I tell them to abstain,” he said. “I tell them if they are ever going to use it, to use it after 26.”

Clinicians also should understand dosages to provide the optimal guidance to their patients who use cannabis.

“People often have no idea how much cannabis they are taking,” especially when using vape cartridges, Dr. Singh said. “If you don’t know, you can’t tell patients about the harms – and if you tell them the wrong information, they will write you off.”

Dr. Singh said he advises his patients to avoid using cannabis vapes or dabbing pens. Both can contain much higher levels of THC than dried flower or edible forms of the drug. He also says patients should stick with low concentrations and use products that contain CBD, which some studies have shown has a protective effect against CIP, although other studies have found that CBD can induce anxiety.

He also tells patients to buy from legal dispensaries and to avoid buying street products that may have methamphetamine or fentanyl mixed in.

Despite the risks, Dr. Singh said legalization can reduce the stigma associated with cannabis use and may prompt patients to be honest with their clinicians. Dr. Singh recalled a 28-year-old patient who was using cannabis to alleviate her arthritic pain. She also was taking a transplant medication, which carried potential side effects of delirium, generalized anxiety disorder, and hallucinosis. After doubling her THC dose, the patient experienced severe anxiety and paranoia.

Dr. Singh’s patient paid him a visit and asked for help. Dr. Singh told her to reduce the dose and to keep track of how she felt. If she continued to feel anxious and paranoid, he recommended that she switch to CBD instead.

“I think education and knowledge is liberating,” Dr. Singh said. “Legalization and frank conversations help people understand how to use a product – and right now, I think that’s lacking.”
 

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

The antipsychotic clozapine appears to guard against suicide for patients with treatment-resistant schizophrenia, results of an autopsy study suggest.

Investigators reviewed over 53,000 autopsy records, including over 600 from individuals whose autopsies revealed the presence of the antipsychotics clozapine or olanzapine, and found that those who took clozapine were significantly less likely to have died by suicide, compared with their counterparts who were taking olanzapine.

“Clozapine is an important and effective antisuicide medicine and should be strongly considered for treatment-resistant psychotic disorders, especially when the patient may be at risk for suicide,” study investigator Paul Nestadt, MD, associate professor, department of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, told this news organization.

The study was published online in The Journal of Clinical Psychiatry.
 

Underutilized medication

Clozapine is the only medication indicated for treatment-resistant schizophrenia and is considered “the most efficacious antipsychotic,” the investigators note. Unfortunately, it has “long been underutilized” for several reasons, including prescriber hesitancy and concerns about side effects.

The authors note that its mechanism of action and the basis for superior efficacy are “still poorly understood” but “may extend beyond neurotransmitter receptor binding.”

Importantly, it may have a beneficial impact on domains other than positive symptoms of schizophrenia, including suicidality. Several studies have shown that it’s beneficial in this regard, but it is “unclear whether the unique antisuicidal properties of clozapine are related to better symptom control ... or to the closer monitoring and follow-up mandated for clozapine use,” they note.

A previous trial, the International Suicide Prevention Trial (InterSePT), demonstrated that clozapine is associated with a greater reduction in suicidality, and the findings “led to an FDA indication for clozapine in reducing the risk of recurrent suicidal behavior.”

However, the authors note, “in the severely ill populations in these studies, it is difficult to be certain about patients’ adherence to prescribed clozapine.”

“Other studies, such as InterSePT, have shown some evidence of clozapine working to reduce suicide-related outcomes, such as attempts or suicidal ideation, but few have been sufficiently powered to measure an effect on actual suicide deaths,” said Dr. Nestadt.

‘Untapped resource’

Of 53,133 decedents, olanzapine or clozapine was detected in the blood of 621 persons (n = 571 and n = 50, respectively).

There were no significant differences in age, sex, race, or urban residence between the decedents who were treated with olanzapine and those who received clozapine.

The odds of a death by suicide in those treated with clozapine were less than half of the odds among decedents who had been treated with olanzapine (odds ratio, 0.47; 95% confidence interval, 0.26-0.84; P = .011).

In sensitivity analyses, the investigators reanalyzed the data to compare clozapine with other antipsychotics, including chlorpromazine, thioridazine, quetiapine, and olanzapine, and the results were similar. The odds of suicide (compared with accident) in those taking clozapine were much lower than in those taking any other tested antipsychotics individually or in combination (OR, 0.42; 95% CI, 0.24-0.73; P = .002).

Dr. Nestadt outlined several hypotheses regarding the mechanism of clozapine’s antisuicidal properties.

“Most theories stem from the differences in its receptor affinity, compared [with] the other neuroleptics,” he said. “In addition to the more typical dopaminergic blockade seen in neuroleptics, clozapine enhances serotonin release and greatly increases peripheral norepinephrine.”

This has been shown to “grant clozapine a greater antidepressant effect than other neuroleptics while also potentially decreasing aggression and impulsivity, which are both strongly associated with suicide risk,” he said.

Clozapine may also “work to reduce the inflammation-triggered activation of the kynurenine pathway, which otherwise contributes to serotonin depletion,” he added.

He noted that some studies have shown that as many as 1 in 10 patients with schizophrenia die by suicide, “so addressing this risk is paramount,” and that clozapine can play an important role in this.

The authors note that the findings “also highlight the utility of state-wide autopsy records, an untapped resource for investigating the potential protective effect of psychiatric medications on suicide at a population level.

“Importantly, we can be certain that this was not an issue of nonadherence to treatment in either group, which is a common issue in the use of these drugs because, instead of prescription records or self-report, we used actual measurements of drug presence in decedents’ blood at death,” said Dr. Nestadt.
 

‘Strongly suggestive’ data

Commenting on the study, Maria Oquendo, MD, PhD, Ruth Meltzer Professor and chair of psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, said most work on antisuicidal psychopharmacologic approaches “focuses on suicidal ideation or suicide attempts, due to the rarity of suicide death, even in high-risk populations.”

“Showing that clozapine may decrease risk for the most dreaded outcome of schizophrenia – suicide – is critically important,” said Dr. Oquendo, past president of the American Psychiatric Association.

Nevertheless, some questions remain, said Dr. Oquendo, who was not involved with the study. “Comparison of suicides to only accidental deaths has limitations. Many individuals who die due to accidents, like many suicides, are not similar to the general population,” she added.

However, she acknowledged, the data are strongly suggestive that clozapine protects against suicide.

“While not definitive, ideally these findings will stimulate changes in prescribing practices which may be lifesaving both literally – in terms of preventing suicides – and figuratively, given the drug’s effect on symptoms that impact quality of life and functioning,” said Dr. Oquendo.

The study received no funding or support. Dr. Nestadt is supported by the American Foundation for Suicide prevention and the National Institute on Drug Abuse. The other authors’ disclosures are listed in the original article. Dr. Oquendo receives royalties from the Research Foundation for Mental Hygiene for the commercial use of the Columbia Suicide Severity Rating Scale. She serves as an advisor to Alkermes, Mind Medicine, Sage Therapeutics, St. George’s University, and Fundacion Jimenez Diaz. Her family owns stock in Bristol-Myers Squibb.

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

The antipsychotic clozapine appears to guard against suicide for patients with treatment-resistant schizophrenia, results of an autopsy study suggest.

Investigators reviewed over 53,000 autopsy records, including over 600 from individuals whose autopsies revealed the presence of the antipsychotics clozapine or olanzapine, and found that those who took clozapine were significantly less likely to have died by suicide, compared with their counterparts who were taking olanzapine.

“Clozapine is an important and effective antisuicide medicine and should be strongly considered for treatment-resistant psychotic disorders, especially when the patient may be at risk for suicide,” study investigator Paul Nestadt, MD, associate professor, department of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, told this news organization.

The study was published online in The Journal of Clinical Psychiatry.
 

Underutilized medication

Clozapine is the only medication indicated for treatment-resistant schizophrenia and is considered “the most efficacious antipsychotic,” the investigators note. Unfortunately, it has “long been underutilized” for several reasons, including prescriber hesitancy and concerns about side effects.

The authors note that its mechanism of action and the basis for superior efficacy are “still poorly understood” but “may extend beyond neurotransmitter receptor binding.”

Importantly, it may have a beneficial impact on domains other than positive symptoms of schizophrenia, including suicidality. Several studies have shown that it’s beneficial in this regard, but it is “unclear whether the unique antisuicidal properties of clozapine are related to better symptom control ... or to the closer monitoring and follow-up mandated for clozapine use,” they note.

A previous trial, the International Suicide Prevention Trial (InterSePT), demonstrated that clozapine is associated with a greater reduction in suicidality, and the findings “led to an FDA indication for clozapine in reducing the risk of recurrent suicidal behavior.”

However, the authors note, “in the severely ill populations in these studies, it is difficult to be certain about patients’ adherence to prescribed clozapine.”

“Other studies, such as InterSePT, have shown some evidence of clozapine working to reduce suicide-related outcomes, such as attempts or suicidal ideation, but few have been sufficiently powered to measure an effect on actual suicide deaths,” said Dr. Nestadt.

‘Untapped resource’

Of 53,133 decedents, olanzapine or clozapine was detected in the blood of 621 persons (n = 571 and n = 50, respectively).

There were no significant differences in age, sex, race, or urban residence between the decedents who were treated with olanzapine and those who received clozapine.

The odds of a death by suicide in those treated with clozapine were less than half of the odds among decedents who had been treated with olanzapine (odds ratio, 0.47; 95% confidence interval, 0.26-0.84; P = .011).

In sensitivity analyses, the investigators reanalyzed the data to compare clozapine with other antipsychotics, including chlorpromazine, thioridazine, quetiapine, and olanzapine, and the results were similar. The odds of suicide (compared with accident) in those taking clozapine were much lower than in those taking any other tested antipsychotics individually or in combination (OR, 0.42; 95% CI, 0.24-0.73; P = .002).

Dr. Nestadt outlined several hypotheses regarding the mechanism of clozapine’s antisuicidal properties.

“Most theories stem from the differences in its receptor affinity, compared [with] the other neuroleptics,” he said. “In addition to the more typical dopaminergic blockade seen in neuroleptics, clozapine enhances serotonin release and greatly increases peripheral norepinephrine.”

This has been shown to “grant clozapine a greater antidepressant effect than other neuroleptics while also potentially decreasing aggression and impulsivity, which are both strongly associated with suicide risk,” he said.

Clozapine may also “work to reduce the inflammation-triggered activation of the kynurenine pathway, which otherwise contributes to serotonin depletion,” he added.

He noted that some studies have shown that as many as 1 in 10 patients with schizophrenia die by suicide, “so addressing this risk is paramount,” and that clozapine can play an important role in this.

The authors note that the findings “also highlight the utility of state-wide autopsy records, an untapped resource for investigating the potential protective effect of psychiatric medications on suicide at a population level.

“Importantly, we can be certain that this was not an issue of nonadherence to treatment in either group, which is a common issue in the use of these drugs because, instead of prescription records or self-report, we used actual measurements of drug presence in decedents’ blood at death,” said Dr. Nestadt.
 

‘Strongly suggestive’ data

Commenting on the study, Maria Oquendo, MD, PhD, Ruth Meltzer Professor and chair of psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, said most work on antisuicidal psychopharmacologic approaches “focuses on suicidal ideation or suicide attempts, due to the rarity of suicide death, even in high-risk populations.”

“Showing that clozapine may decrease risk for the most dreaded outcome of schizophrenia – suicide – is critically important,” said Dr. Oquendo, past president of the American Psychiatric Association.

Nevertheless, some questions remain, said Dr. Oquendo, who was not involved with the study. “Comparison of suicides to only accidental deaths has limitations. Many individuals who die due to accidents, like many suicides, are not similar to the general population,” she added.

However, she acknowledged, the data are strongly suggestive that clozapine protects against suicide.

“While not definitive, ideally these findings will stimulate changes in prescribing practices which may be lifesaving both literally – in terms of preventing suicides – and figuratively, given the drug’s effect on symptoms that impact quality of life and functioning,” said Dr. Oquendo.

The study received no funding or support. Dr. Nestadt is supported by the American Foundation for Suicide prevention and the National Institute on Drug Abuse. The other authors’ disclosures are listed in the original article. Dr. Oquendo receives royalties from the Research Foundation for Mental Hygiene for the commercial use of the Columbia Suicide Severity Rating Scale. She serves as an advisor to Alkermes, Mind Medicine, Sage Therapeutics, St. George’s University, and Fundacion Jimenez Diaz. Her family owns stock in Bristol-Myers Squibb.

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

The antipsychotic clozapine appears to guard against suicide for patients with treatment-resistant schizophrenia, results of an autopsy study suggest.

Investigators reviewed over 53,000 autopsy records, including over 600 from individuals whose autopsies revealed the presence of the antipsychotics clozapine or olanzapine, and found that those who took clozapine were significantly less likely to have died by suicide, compared with their counterparts who were taking olanzapine.

“Clozapine is an important and effective antisuicide medicine and should be strongly considered for treatment-resistant psychotic disorders, especially when the patient may be at risk for suicide,” study investigator Paul Nestadt, MD, associate professor, department of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, told this news organization.

The study was published online in The Journal of Clinical Psychiatry.
 

Underutilized medication

Clozapine is the only medication indicated for treatment-resistant schizophrenia and is considered “the most efficacious antipsychotic,” the investigators note. Unfortunately, it has “long been underutilized” for several reasons, including prescriber hesitancy and concerns about side effects.

The authors note that its mechanism of action and the basis for superior efficacy are “still poorly understood” but “may extend beyond neurotransmitter receptor binding.”

Importantly, it may have a beneficial impact on domains other than positive symptoms of schizophrenia, including suicidality. Several studies have shown that it’s beneficial in this regard, but it is “unclear whether the unique antisuicidal properties of clozapine are related to better symptom control ... or to the closer monitoring and follow-up mandated for clozapine use,” they note.

A previous trial, the International Suicide Prevention Trial (InterSePT), demonstrated that clozapine is associated with a greater reduction in suicidality, and the findings “led to an FDA indication for clozapine in reducing the risk of recurrent suicidal behavior.”

However, the authors note, “in the severely ill populations in these studies, it is difficult to be certain about patients’ adherence to prescribed clozapine.”

“Other studies, such as InterSePT, have shown some evidence of clozapine working to reduce suicide-related outcomes, such as attempts or suicidal ideation, but few have been sufficiently powered to measure an effect on actual suicide deaths,” said Dr. Nestadt.

‘Untapped resource’

Of 53,133 decedents, olanzapine or clozapine was detected in the blood of 621 persons (n = 571 and n = 50, respectively).

There were no significant differences in age, sex, race, or urban residence between the decedents who were treated with olanzapine and those who received clozapine.

The odds of a death by suicide in those treated with clozapine were less than half of the odds among decedents who had been treated with olanzapine (odds ratio, 0.47; 95% confidence interval, 0.26-0.84; P = .011).

In sensitivity analyses, the investigators reanalyzed the data to compare clozapine with other antipsychotics, including chlorpromazine, thioridazine, quetiapine, and olanzapine, and the results were similar. The odds of suicide (compared with accident) in those taking clozapine were much lower than in those taking any other tested antipsychotics individually or in combination (OR, 0.42; 95% CI, 0.24-0.73; P = .002).

Dr. Nestadt outlined several hypotheses regarding the mechanism of clozapine’s antisuicidal properties.

“Most theories stem from the differences in its receptor affinity, compared [with] the other neuroleptics,” he said. “In addition to the more typical dopaminergic blockade seen in neuroleptics, clozapine enhances serotonin release and greatly increases peripheral norepinephrine.”

This has been shown to “grant clozapine a greater antidepressant effect than other neuroleptics while also potentially decreasing aggression and impulsivity, which are both strongly associated with suicide risk,” he said.

Clozapine may also “work to reduce the inflammation-triggered activation of the kynurenine pathway, which otherwise contributes to serotonin depletion,” he added.

He noted that some studies have shown that as many as 1 in 10 patients with schizophrenia die by suicide, “so addressing this risk is paramount,” and that clozapine can play an important role in this.

The authors note that the findings “also highlight the utility of state-wide autopsy records, an untapped resource for investigating the potential protective effect of psychiatric medications on suicide at a population level.

“Importantly, we can be certain that this was not an issue of nonadherence to treatment in either group, which is a common issue in the use of these drugs because, instead of prescription records or self-report, we used actual measurements of drug presence in decedents’ blood at death,” said Dr. Nestadt.
 

‘Strongly suggestive’ data

Commenting on the study, Maria Oquendo, MD, PhD, Ruth Meltzer Professor and chair of psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, said most work on antisuicidal psychopharmacologic approaches “focuses on suicidal ideation or suicide attempts, due to the rarity of suicide death, even in high-risk populations.”

“Showing that clozapine may decrease risk for the most dreaded outcome of schizophrenia – suicide – is critically important,” said Dr. Oquendo, past president of the American Psychiatric Association.

Nevertheless, some questions remain, said Dr. Oquendo, who was not involved with the study. “Comparison of suicides to only accidental deaths has limitations. Many individuals who die due to accidents, like many suicides, are not similar to the general population,” she added.

However, she acknowledged, the data are strongly suggestive that clozapine protects against suicide.

“While not definitive, ideally these findings will stimulate changes in prescribing practices which may be lifesaving both literally – in terms of preventing suicides – and figuratively, given the drug’s effect on symptoms that impact quality of life and functioning,” said Dr. Oquendo.

The study received no funding or support. Dr. Nestadt is supported by the American Foundation for Suicide prevention and the National Institute on Drug Abuse. The other authors’ disclosures are listed in the original article. Dr. Oquendo receives royalties from the Research Foundation for Mental Hygiene for the commercial use of the Columbia Suicide Severity Rating Scale. She serves as an advisor to Alkermes, Mind Medicine, Sage Therapeutics, St. George’s University, and Fundacion Jimenez Diaz. Her family owns stock in Bristol-Myers Squibb.

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

Psychiatrists practice in a wide array of ways. We approach our work and our patients with beliefs and preconceptions that develop over time. Our training has significant influence, though our own personalities and biases also affect our understanding.

Psychiatrists have philosophical lenses through which they see patients. We can reflect and see some standard archetypes. We are familiar with the reductionistic pharmacologist, the somatic treatment specialist, the psychodynamic ‘guru,’ and the medicolegally paralyzed practitioner. It is without judgment that we lay these out, for our very point is that we have these constituent parts within our own clinical identities. The intensity with which we subscribe to these clinical sensibilities could contribute to a biased orthodoxy.

Orthodoxy can be defined as an accepted theory that stems from an authoritative entity. This is a well-known phenomenon that continues to be visible. For example, one can quickly peruse psychodynamic literature to find one school of thought criticizing another. It is not without some confrontation and even interpersonal rifts that the lineage of psychoanalytic theory has evolved. This has always been of interest to us. A core facet of psychoanalysis is empathy, truly knowing the inner state of a different person. And yet, the very bastions of this clinical sensibility frequently resort to veiled attacks on those in their field who have opposing views. It then begs the question: If even enlightened institutions fail at a nonjudgmental approach toward their colleagues, what hope is there for the rest of us clinicians, mired in the thick of day-to-day clinical practice?

It is our contention that the odds are against us. Even the aforementioned critique of psychoanalytic orthodoxy is just another example of how we humans organize our experience. Even as we write an article in argument against unbridled critique, we find it difficult to do so without engaging in it. For to criticize another is to help shore up our own personal identities. This is especially the case when clinicians deal with issues that we feel strongly about. The human psyche has a need to organize its experience, as “our experience of ourselves is fundamental to how we operate in the world. Our subjective experience is the phenomenology of all that one might be aware of.”¹

In this vein, we would like to cite attribution theory. This is a view of human behavior within social psychology. The Austrian psychologist Fritz Heider, PhD, investigated “the domain of social interactions, wondering how people perceive each other in interaction and especially how they make sense of each other’s behavior.”² Attribution theory suggests that as humans organize our social interactions, we may make two basic assumptions. One is that our own behavior is highly affected by an environment that is beyond our control. The second is that when judging the behavior of others, we are more likely to attribute it to internal traits that they have. A classic example is automobile traffic. When we see someone driving erratically, we are more likely to blame them for being an inherently bad driver. However, if attention is called to our own driving, we are more likely to cite external factors such as rush hour, a bad driver around us, or a faulty vehicle.

We would like to reference one last model of human behavior. It has become customary within the field of neuroscience to view the brain as a predictive organ: “Theories of prediction in perception, action, and learning suggest that the brain serves to reduce the discrepancies between expectation and actual experience, i.e., by reducing the prediction error.”³ Perception itself has recently been described as a controlled hallucination, where the brain makes predictions of what it thinks it is about to see based on past experiences. Visual stimulus ultimately takes time to enter our eyes and be processed in the brain – “predictions would need to preactivate neural representations that would typically be driven by sensory input, before the actual arrival of that input.”⁴ It thus seems to be an inherent method of the brain to anticipate visual and even social events to help human beings sustain themselves.

Having spoken of a psychoanalytic conceptualization of self-organization, the theory of attribution, and research into social neuroscience, we turn our attention back to the central question that this article would like to address. Can we, as clinicians, truly put ourselves into the mindset of our colleagues and appreciate, and even agree with, the philosophies and methodologies of our fellow psychiatrists?

When we find ourselves busy in rote clinical practice, we believe the likelihood of intercollegiate mentalization is low; our ability to relate to our peers becomes strained. We ultimately do not practice in a vacuum. Psychiatrists, even those in a solo private practice, are ultimately part of a community of providers who, more or less, follow some emergent ‘standard of care.’ This can be a vague concept; but one that takes on a concrete form in the minds of certain clinicians and certainly in the setting of a medicolegal court. Yet, the psychiatrists that we know all have very stereotyped ways of practice. And at the heart of it, we all think that we are right.

We can use polypharmacy as an example. Imagine that you have a new patient intake, who tells you that they are transferring care from another psychiatrist. They inform you of their medication regimen. This patient presents on eight or more psychotropics. Many of us may have a visceral reaction at this point and, following the aforementioned attribution theory, we may ask ourselves what ‘quack’ of a doctor would do this. Yet some among us would think that a very competent psychopharmacologist was daring enough to use the full armamentarium of psychopharmacology to help this patient, who must be treatment refractory.

When speaking with such a patient, we would be quick to reflect on our own parsimonious use of medications. We would tell ourselves that we are responsible providers and would be quick to recommend discontinuation of medications. This would help us feel better about ourselves, and would of course assuage the ever-present medicolegal ‘big brother’ in our minds. It is through this very process that we affirm our self-identities. For if this patient’s previous physician was a bad psychiatrist, then we are a good psychiatrist. It is through this process that our clinical selves find confirmation.

We do not mean to reduce the complexities of human behavior to quick stereotypes. However, it is our belief that when confronted with clinical or philosophical disputes with our colleagues, the basic rules of human behavior will attempt to dissolve and override efforts at mentalization, collegiality, or interpersonal sensitivity. For to accept a clinical practice view that is different from ours would be akin to giving up the essence of our clinical identities. It could be compared to the fragmentation process of a vulnerable psyche when confronted with a reality that is at odds with preconceived notions and experiences.

While we may be able to appreciate the nuances and sensibilities of another provider, we believe it would be particularly difficult for most of us to actually attempt to practice in a fashion that is not congruent with our own organizers of experience. Whether or not our practice style is ‘perfect,’ it has worked for us. Social neuroscience and our understanding of the organization of the self would predict that we would hold onto our way of practice with all the mind’s defenses. Externalization, denial, and projection could all be called into action in this battle against existential fragmentation.

Do we seek to portray a clinical world where there is no hope for genuine modeling of clinical sensibilities to other psychiatrists? That is not our intention. Yet it seems that many of the theoretical frameworks that we subscribe to argue against this possibility. We would be hypocritical if we did not here state that our own theoretical frameworks are yet other examples of “organizers of experience.” Attribution theory, intersubjectivity, and social neuroscience are simply our ways of organizing the chaos of perceptions, ideas, and intricacies of human behavior.

If we accept that psychiatrists, like all human beings, are trapped in a subjective experience, then we can be more playful and flexible when interacting with our colleagues. We do not have to be as defensive of our practices and accusatory of others. If we practice daily according to some orthodoxy, then we color our experiences of the patient and of our colleagues’ ways of practice. We automatically start off on the wrong foot. And yet, to give up this orthodoxy would, by definition, be disorganizing and fragmenting to us. For as Nietzsche said, “truth is an illusion without which a certain species could not survive.”⁵

Dr. Khalafian practices full time as a general outpatient psychiatrist. He trained at the University of California, San Diego, for his psychiatric residency and currently works as a telepsychiatrist, serving an outpatient clinic population in northern California. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Badre and Dr. Khalafian have no conflicts of interest.

References

1. Buirski P and Haglund P. Making sense together: The intersubjective approach to psychotherapy. Northvale, NJ: Jason Aronson; 2001.

2. Malle BF. Attribution theories: How people make sense of behavior. In Chadee D (ed.), Theories in social psychology. pp. 72-95. Wiley-Blackwell; 2011.

3. Brown EC and Brune M. The role of prediction in social neuroscience. Front Hum Neurosci. 2012 May 24;6:147. doi: 10.3389/fnhum.2012.00147.

4. Blom T et al. Predictions drive neural representations of visual events ahead of incoming sensory information. Proc Natl Acad Sci USA. 2020 Mar 31;117(13):7510-7515. doi: 10.1073/pnas.1917777117.

5. Yalom I. The Gift of Therapy. Harper Perennial; 2002.

Psychiatrists practice in a wide array of ways. We approach our work and our patients with beliefs and preconceptions that develop over time. Our training has significant influence, though our own personalities and biases also affect our understanding.

Psychiatrists have philosophical lenses through which they see patients. We can reflect and see some standard archetypes. We are familiar with the reductionistic pharmacologist, the somatic treatment specialist, the psychodynamic ‘guru,’ and the medicolegally paralyzed practitioner. It is without judgment that we lay these out, for our very point is that we have these constituent parts within our own clinical identities. The intensity with which we subscribe to these clinical sensibilities could contribute to a biased orthodoxy.

Orthodoxy can be defined as an accepted theory that stems from an authoritative entity. This is a well-known phenomenon that continues to be visible. For example, one can quickly peruse psychodynamic literature to find one school of thought criticizing another. It is not without some confrontation and even interpersonal rifts that the lineage of psychoanalytic theory has evolved. This has always been of interest to us. A core facet of psychoanalysis is empathy, truly knowing the inner state of a different person. And yet, the very bastions of this clinical sensibility frequently resort to veiled attacks on those in their field who have opposing views. It then begs the question: If even enlightened institutions fail at a nonjudgmental approach toward their colleagues, what hope is there for the rest of us clinicians, mired in the thick of day-to-day clinical practice?

It is our contention that the odds are against us. Even the aforementioned critique of psychoanalytic orthodoxy is just another example of how we humans organize our experience. Even as we write an article in argument against unbridled critique, we find it difficult to do so without engaging in it. For to criticize another is to help shore up our own personal identities. This is especially the case when clinicians deal with issues that we feel strongly about. The human psyche has a need to organize its experience, as “our experience of ourselves is fundamental to how we operate in the world. Our subjective experience is the phenomenology of all that one might be aware of.”¹

In this vein, we would like to cite attribution theory. This is a view of human behavior within social psychology. The Austrian psychologist Fritz Heider, PhD, investigated “the domain of social interactions, wondering how people perceive each other in interaction and especially how they make sense of each other’s behavior.”² Attribution theory suggests that as humans organize our social interactions, we may make two basic assumptions. One is that our own behavior is highly affected by an environment that is beyond our control. The second is that when judging the behavior of others, we are more likely to attribute it to internal traits that they have. A classic example is automobile traffic. When we see someone driving erratically, we are more likely to blame them for being an inherently bad driver. However, if attention is called to our own driving, we are more likely to cite external factors such as rush hour, a bad driver around us, or a faulty vehicle.

We would like to reference one last model of human behavior. It has become customary within the field of neuroscience to view the brain as a predictive organ: “Theories of prediction in perception, action, and learning suggest that the brain serves to reduce the discrepancies between expectation and actual experience, i.e., by reducing the prediction error.”³ Perception itself has recently been described as a controlled hallucination, where the brain makes predictions of what it thinks it is about to see based on past experiences. Visual stimulus ultimately takes time to enter our eyes and be processed in the brain – “predictions would need to preactivate neural representations that would typically be driven by sensory input, before the actual arrival of that input.”⁴ It thus seems to be an inherent method of the brain to anticipate visual and even social events to help human beings sustain themselves.

Having spoken of a psychoanalytic conceptualization of self-organization, the theory of attribution, and research into social neuroscience, we turn our attention back to the central question that this article would like to address. Can we, as clinicians, truly put ourselves into the mindset of our colleagues and appreciate, and even agree with, the philosophies and methodologies of our fellow psychiatrists?

When we find ourselves busy in rote clinical practice, we believe the likelihood of intercollegiate mentalization is low; our ability to relate to our peers becomes strained. We ultimately do not practice in a vacuum. Psychiatrists, even those in a solo private practice, are ultimately part of a community of providers who, more or less, follow some emergent ‘standard of care.’ This can be a vague concept; but one that takes on a concrete form in the minds of certain clinicians and certainly in the setting of a medicolegal court. Yet, the psychiatrists that we know all have very stereotyped ways of practice. And at the heart of it, we all think that we are right.

We can use polypharmacy as an example. Imagine that you have a new patient intake, who tells you that they are transferring care from another psychiatrist. They inform you of their medication regimen. This patient presents on eight or more psychotropics. Many of us may have a visceral reaction at this point and, following the aforementioned attribution theory, we may ask ourselves what ‘quack’ of a doctor would do this. Yet some among us would think that a very competent psychopharmacologist was daring enough to use the full armamentarium of psychopharmacology to help this patient, who must be treatment refractory.

When speaking with such a patient, we would be quick to reflect on our own parsimonious use of medications. We would tell ourselves that we are responsible providers and would be quick to recommend discontinuation of medications. This would help us feel better about ourselves, and would of course assuage the ever-present medicolegal ‘big brother’ in our minds. It is through this very process that we affirm our self-identities. For if this patient’s previous physician was a bad psychiatrist, then we are a good psychiatrist. It is through this process that our clinical selves find confirmation.

We do not mean to reduce the complexities of human behavior to quick stereotypes. However, it is our belief that when confronted with clinical or philosophical disputes with our colleagues, the basic rules of human behavior will attempt to dissolve and override efforts at mentalization, collegiality, or interpersonal sensitivity. For to accept a clinical practice view that is different from ours would be akin to giving up the essence of our clinical identities. It could be compared to the fragmentation process of a vulnerable psyche when confronted with a reality that is at odds with preconceived notions and experiences.

While we may be able to appreciate the nuances and sensibilities of another provider, we believe it would be particularly difficult for most of us to actually attempt to practice in a fashion that is not congruent with our own organizers of experience. Whether or not our practice style is ‘perfect,’ it has worked for us. Social neuroscience and our understanding of the organization of the self would predict that we would hold onto our way of practice with all the mind’s defenses. Externalization, denial, and projection could all be called into action in this battle against existential fragmentation.

Do we seek to portray a clinical world where there is no hope for genuine modeling of clinical sensibilities to other psychiatrists? That is not our intention. Yet it seems that many of the theoretical frameworks that we subscribe to argue against this possibility. We would be hypocritical if we did not here state that our own theoretical frameworks are yet other examples of “organizers of experience.” Attribution theory, intersubjectivity, and social neuroscience are simply our ways of organizing the chaos of perceptions, ideas, and intricacies of human behavior.

If we accept that psychiatrists, like all human beings, are trapped in a subjective experience, then we can be more playful and flexible when interacting with our colleagues. We do not have to be as defensive of our practices and accusatory of others. If we practice daily according to some orthodoxy, then we color our experiences of the patient and of our colleagues’ ways of practice. We automatically start off on the wrong foot. And yet, to give up this orthodoxy would, by definition, be disorganizing and fragmenting to us. For as Nietzsche said, “truth is an illusion without which a certain species could not survive.”⁵

Dr. Khalafian practices full time as a general outpatient psychiatrist. He trained at the University of California, San Diego, for his psychiatric residency and currently works as a telepsychiatrist, serving an outpatient clinic population in northern California. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Badre and Dr. Khalafian have no conflicts of interest.

References

1. Buirski P and Haglund P. Making sense together: The intersubjective approach to psychotherapy. Northvale, NJ: Jason Aronson; 2001.

2. Malle BF. Attribution theories: How people make sense of behavior. In Chadee D (ed.), Theories in social psychology. pp. 72-95. Wiley-Blackwell; 2011.

3. Brown EC and Brune M. The role of prediction in social neuroscience. Front Hum Neurosci. 2012 May 24;6:147. doi: 10.3389/fnhum.2012.00147.

4. Blom T et al. Predictions drive neural representations of visual events ahead of incoming sensory information. Proc Natl Acad Sci USA. 2020 Mar 31;117(13):7510-7515. doi: 10.1073/pnas.1917777117.

5. Yalom I. The Gift of Therapy. Harper Perennial; 2002.

Psychiatrists practice in a wide array of ways. We approach our work and our patients with beliefs and preconceptions that develop over time. Our training has significant influence, though our own personalities and biases also affect our understanding.

Psychiatrists have philosophical lenses through which they see patients. We can reflect and see some standard archetypes. We are familiar with the reductionistic pharmacologist, the somatic treatment specialist, the psychodynamic ‘guru,’ and the medicolegally paralyzed practitioner. It is without judgment that we lay these out, for our very point is that we have these constituent parts within our own clinical identities. The intensity with which we subscribe to these clinical sensibilities could contribute to a biased orthodoxy.

Orthodoxy can be defined as an accepted theory that stems from an authoritative entity. This is a well-known phenomenon that continues to be visible. For example, one can quickly peruse psychodynamic literature to find one school of thought criticizing another. It is not without some confrontation and even interpersonal rifts that the lineage of psychoanalytic theory has evolved. This has always been of interest to us. A core facet of psychoanalysis is empathy, truly knowing the inner state of a different person. And yet, the very bastions of this clinical sensibility frequently resort to veiled attacks on those in their field who have opposing views. It then begs the question: If even enlightened institutions fail at a nonjudgmental approach toward their colleagues, what hope is there for the rest of us clinicians, mired in the thick of day-to-day clinical practice?

It is our contention that the odds are against us. Even the aforementioned critique of psychoanalytic orthodoxy is just another example of how we humans organize our experience. Even as we write an article in argument against unbridled critique, we find it difficult to do so without engaging in it. For to criticize another is to help shore up our own personal identities. This is especially the case when clinicians deal with issues that we feel strongly about. The human psyche has a need to organize its experience, as “our experience of ourselves is fundamental to how we operate in the world. Our subjective experience is the phenomenology of all that one might be aware of.”¹

In this vein, we would like to cite attribution theory. This is a view of human behavior within social psychology. The Austrian psychologist Fritz Heider, PhD, investigated “the domain of social interactions, wondering how people perceive each other in interaction and especially how they make sense of each other’s behavior.”² Attribution theory suggests that as humans organize our social interactions, we may make two basic assumptions. One is that our own behavior is highly affected by an environment that is beyond our control. The second is that when judging the behavior of others, we are more likely to attribute it to internal traits that they have. A classic example is automobile traffic. When we see someone driving erratically, we are more likely to blame them for being an inherently bad driver. However, if attention is called to our own driving, we are more likely to cite external factors such as rush hour, a bad driver around us, or a faulty vehicle.

We would like to reference one last model of human behavior. It has become customary within the field of neuroscience to view the brain as a predictive organ: “Theories of prediction in perception, action, and learning suggest that the brain serves to reduce the discrepancies between expectation and actual experience, i.e., by reducing the prediction error.”³ Perception itself has recently been described as a controlled hallucination, where the brain makes predictions of what it thinks it is about to see based on past experiences. Visual stimulus ultimately takes time to enter our eyes and be processed in the brain – “predictions would need to preactivate neural representations that would typically be driven by sensory input, before the actual arrival of that input.”⁴ It thus seems to be an inherent method of the brain to anticipate visual and even social events to help human beings sustain themselves.

Having spoken of a psychoanalytic conceptualization of self-organization, the theory of attribution, and research into social neuroscience, we turn our attention back to the central question that this article would like to address. Can we, as clinicians, truly put ourselves into the mindset of our colleagues and appreciate, and even agree with, the philosophies and methodologies of our fellow psychiatrists?

When we find ourselves busy in rote clinical practice, we believe the likelihood of intercollegiate mentalization is low; our ability to relate to our peers becomes strained. We ultimately do not practice in a vacuum. Psychiatrists, even those in a solo private practice, are ultimately part of a community of providers who, more or less, follow some emergent ‘standard of care.’ This can be a vague concept; but one that takes on a concrete form in the minds of certain clinicians and certainly in the setting of a medicolegal court. Yet, the psychiatrists that we know all have very stereotyped ways of practice. And at the heart of it, we all think that we are right.

We can use polypharmacy as an example. Imagine that you have a new patient intake, who tells you that they are transferring care from another psychiatrist. They inform you of their medication regimen. This patient presents on eight or more psychotropics. Many of us may have a visceral reaction at this point and, following the aforementioned attribution theory, we may ask ourselves what ‘quack’ of a doctor would do this. Yet some among us would think that a very competent psychopharmacologist was daring enough to use the full armamentarium of psychopharmacology to help this patient, who must be treatment refractory.

When speaking with such a patient, we would be quick to reflect on our own parsimonious use of medications. We would tell ourselves that we are responsible providers and would be quick to recommend discontinuation of medications. This would help us feel better about ourselves, and would of course assuage the ever-present medicolegal ‘big brother’ in our minds. It is through this very process that we affirm our self-identities. For if this patient’s previous physician was a bad psychiatrist, then we are a good psychiatrist. It is through this process that our clinical selves find confirmation.

We do not mean to reduce the complexities of human behavior to quick stereotypes. However, it is our belief that when confronted with clinical or philosophical disputes with our colleagues, the basic rules of human behavior will attempt to dissolve and override efforts at mentalization, collegiality, or interpersonal sensitivity. For to accept a clinical practice view that is different from ours would be akin to giving up the essence of our clinical identities. It could be compared to the fragmentation process of a vulnerable psyche when confronted with a reality that is at odds with preconceived notions and experiences.

While we may be able to appreciate the nuances and sensibilities of another provider, we believe it would be particularly difficult for most of us to actually attempt to practice in a fashion that is not congruent with our own organizers of experience. Whether or not our practice style is ‘perfect,’ it has worked for us. Social neuroscience and our understanding of the organization of the self would predict that we would hold onto our way of practice with all the mind’s defenses. Externalization, denial, and projection could all be called into action in this battle against existential fragmentation.

Do we seek to portray a clinical world where there is no hope for genuine modeling of clinical sensibilities to other psychiatrists? That is not our intention. Yet it seems that many of the theoretical frameworks that we subscribe to argue against this possibility. We would be hypocritical if we did not here state that our own theoretical frameworks are yet other examples of “organizers of experience.” Attribution theory, intersubjectivity, and social neuroscience are simply our ways of organizing the chaos of perceptions, ideas, and intricacies of human behavior.

If we accept that psychiatrists, like all human beings, are trapped in a subjective experience, then we can be more playful and flexible when interacting with our colleagues. We do not have to be as defensive of our practices and accusatory of others. If we practice daily according to some orthodoxy, then we color our experiences of the patient and of our colleagues’ ways of practice. We automatically start off on the wrong foot. And yet, to give up this orthodoxy would, by definition, be disorganizing and fragmenting to us. For as Nietzsche said, “truth is an illusion without which a certain species could not survive.”⁵

Dr. Khalafian practices full time as a general outpatient psychiatrist. He trained at the University of California, San Diego, for his psychiatric residency and currently works as a telepsychiatrist, serving an outpatient clinic population in northern California. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Badre and Dr. Khalafian have no conflicts of interest.

References

1. Buirski P and Haglund P. Making sense together: The intersubjective approach to psychotherapy. Northvale, NJ: Jason Aronson; 2001.

2. Malle BF. Attribution theories: How people make sense of behavior. In Chadee D (ed.), Theories in social psychology. pp. 72-95. Wiley-Blackwell; 2011.

3. Brown EC and Brune M. The role of prediction in social neuroscience. Front Hum Neurosci. 2012 May 24;6:147. doi: 10.3389/fnhum.2012.00147.

4. Blom T et al. Predictions drive neural representations of visual events ahead of incoming sensory information. Proc Natl Acad Sci USA. 2020 Mar 31;117(13):7510-7515. doi: 10.1073/pnas.1917777117.

5. Yalom I. The Gift of Therapy. Harper Perennial; 2002.

People who had low hopes from a COVID-19 vaccine reported more negative side effects from the shots in a new study.

It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others. 

In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.

Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.

The research was published in JAMA Network Open.

“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”

More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.

The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
 

A version of this article originally appeared on WebMD.com.

People who had low hopes from a COVID-19 vaccine reported more negative side effects from the shots in a new study.

It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others. 

In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.

Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.

The research was published in JAMA Network Open.

“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”

More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.

The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
 

A version of this article originally appeared on WebMD.com.

People who had low hopes from a COVID-19 vaccine reported more negative side effects from the shots in a new study.

It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others. 

In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.

Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.

The research was published in JAMA Network Open.

“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”

More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.

The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
 

A version of this article originally appeared on WebMD.com.

Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy

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

Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy

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

Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy

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

PARIS – Listening to music via curated playlists at bedtime is effective for depression-related insomnia, although the depression itself is unaffected, new research suggests.

The Music to Improve Sleep Quality in Adults With Depression and Insomnia (MUSTAFI) trial randomly assigned more than 110 outpatients with depression to either a music intervention or a waiting list. Sleep quality and quality of life significantly improved after listening to music for half an hour at bedtime for 4 weeks.

“This is a low-cost, safe intervention that has no side effects and may easily be implemented in psychiatry” along with existing treatments, lead researcher Helle Nystrup Lund, PhD, unit for depression, Aalborg (Denmark) University Hospital, said in an interview.

The findings were presented at the European Psychiatric Association 2023 Congress, and recently published in the Nordic Journal of Psychiatry.
 

Difficult to resolve

The researchers noted that insomnia is common in patients with depression and is “difficult to resolve.”

They noted that, while music is commonly used as a sleep aid and a growing evidence base suggests it has positive effects, there have been few investigations into the effectiveness of music for patients with depression-related insomnia.

To fill this research gap, 112 outpatients with depression and comorbid insomnia who were receiving care at a single center were randomly assigned to either an intervention group or a wait list control group.

Participants in the intervention group listened to music for a minimum of 30 minutes at bedtime for 4 weeks. The music was delivered via the MusicStar app, which is available as a free download from the Apple and Android (Google Play) app stores. The app was developed by Dr. Lund and Lars Rye Bertelsen, a PhD student and music therapist at Aalborg University Hospital.

The app is designed as a multicolored star, with each arm of the star linking to a playlist lasting between 30 minutes and 1 hour. Each color of the star indicates a different tempo of music.

Blue playlists, Dr. Lund explained, offer the quietest music, green is more lively, and red is the most dynamic. Gray playlists linked to project-related soundtracks, such as summer rain.

Dr. Lund said organizing the playlists by stimuli and color code, instead of genre, allows users to regulate their level of arousal and makes the music choice intuitive and easy.

She said that the genres of music include New Age, folk, pop, classical, and film soundtracks, “but no hard rock.”

“There’s actually a quite large selection of music available, because studies show that individual choice is important, as are personal preferences,” she said, adding that the endless choices offered by streaming services can cause confusion.

“So we made curated playlists and designed them with well-known pieces, but also with newly composed music not associated with anything,” Dr. Lund said.

Participants were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Hamilton Depression Rating Scale, and two World Health Organization well-being questionnaires (WHO-5, WHOQOL-BREF), as well as actigraphy.

Results showed that, at 4 weeks, participants in the intervention group experienced significant improvements in sleep quality in comparison with control persons. The effect size for the PSQI was –2.1, and for quality of life on the WHO-5, the effect size was 8.4.

A subanalysis revealed that the length of nocturnal sleep in the intervention group increased by an average of 18 minutes during the study from a baseline of approximately 5 hours per night, said Dr. Lund.

However, there were no changes in actigraphy measurements and no significant improvements in HAMD-17 scores.

Dr. Lund said that, on the basis of these positive findings, music intervention as a sleep aid is now offered at Aalborg University Hospital to patients with depression-related insomnia.
 

Clinically meaningful?

Commenting on the findings, Gerald J. Haeffel, PhD, department of psychology, University of Notre Dame, South Bend, Ind., said that overall, the study showed there was a change in sleep-quality and quality of life scores of “about 10% in each.”

“This, on the surface, would seem to be a meaningful change,” although it is less clear whether it is “clinically meaningful.” Perhaps it is, “but it would be nice to have more information.”

It would be useful, he said, to “show the means for each group pre- to postintervention, along with standard deviations,” he added.

Dr. Haeffel added that on the basis of current results, it isn’t possible to determine whether individuals’ control over music choice is important.

“We have no idea if ‘choice’ or length of playlist had any causal role in the results. One would need to run a study with the same playlist, but in one group people have to listen to whatever song comes on versus another condition in which they get to choose a song off the same list,” he said.

He noted that his group conducted a study in which highly popular music that was chosen by individual participants was found to have a positive effect. Even so, he said, “we could not determine if it was ‘choice’ or ‘popularity’ that caused the positive effects of music.”

In addition, he said, the reason music has a positive effect on insomnia remains unclear.

“It is not because it helped with depression, and it’s not because it’s actually changing objective sleep parameters. It could be that it improves mood right before bed or helps distract people right before bed. At the same time, it could also just be a placebo effect,” said Dr. Haeffel.

In addition, he said, it’s important to note that the music intervention had no comparator, so “maybe just doing something different or getting to talk with researchers created the effect and has nothing to do with music.”

Overall, he believes that there are “not enough data” to use the sleep intervention that was employed in the current study “as primary intervention, but future work could show its usefulness as a supplement.”

Dr. Lund and Mr. Bertelsen reported ownership and sales of the MusicStar app. Dr. Haeffel reported no relevant financial relationships.

PARIS – Listening to music via curated playlists at bedtime is effective for depression-related insomnia, although the depression itself is unaffected, new research suggests.

The Music to Improve Sleep Quality in Adults With Depression and Insomnia (MUSTAFI) trial randomly assigned more than 110 outpatients with depression to either a music intervention or a waiting list. Sleep quality and quality of life significantly improved after listening to music for half an hour at bedtime for 4 weeks.

“This is a low-cost, safe intervention that has no side effects and may easily be implemented in psychiatry” along with existing treatments, lead researcher Helle Nystrup Lund, PhD, unit for depression, Aalborg (Denmark) University Hospital, said in an interview.

The findings were presented at the European Psychiatric Association 2023 Congress, and recently published in the Nordic Journal of Psychiatry.
 

Difficult to resolve

The researchers noted that insomnia is common in patients with depression and is “difficult to resolve.”

They noted that, while music is commonly used as a sleep aid and a growing evidence base suggests it has positive effects, there have been few investigations into the effectiveness of music for patients with depression-related insomnia.

To fill this research gap, 112 outpatients with depression and comorbid insomnia who were receiving care at a single center were randomly assigned to either an intervention group or a wait list control group.

Participants in the intervention group listened to music for a minimum of 30 minutes at bedtime for 4 weeks. The music was delivered via the MusicStar app, which is available as a free download from the Apple and Android (Google Play) app stores. The app was developed by Dr. Lund and Lars Rye Bertelsen, a PhD student and music therapist at Aalborg University Hospital.

The app is designed as a multicolored star, with each arm of the star linking to a playlist lasting between 30 minutes and 1 hour. Each color of the star indicates a different tempo of music.

Blue playlists, Dr. Lund explained, offer the quietest music, green is more lively, and red is the most dynamic. Gray playlists linked to project-related soundtracks, such as summer rain.

Dr. Lund said organizing the playlists by stimuli and color code, instead of genre, allows users to regulate their level of arousal and makes the music choice intuitive and easy.

She said that the genres of music include New Age, folk, pop, classical, and film soundtracks, “but no hard rock.”

“There’s actually a quite large selection of music available, because studies show that individual choice is important, as are personal preferences,” she said, adding that the endless choices offered by streaming services can cause confusion.

“So we made curated playlists and designed them with well-known pieces, but also with newly composed music not associated with anything,” Dr. Lund said.

Participants were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Hamilton Depression Rating Scale, and two World Health Organization well-being questionnaires (WHO-5, WHOQOL-BREF), as well as actigraphy.

Results showed that, at 4 weeks, participants in the intervention group experienced significant improvements in sleep quality in comparison with control persons. The effect size for the PSQI was –2.1, and for quality of life on the WHO-5, the effect size was 8.4.

A subanalysis revealed that the length of nocturnal sleep in the intervention group increased by an average of 18 minutes during the study from a baseline of approximately 5 hours per night, said Dr. Lund.

However, there were no changes in actigraphy measurements and no significant improvements in HAMD-17 scores.

Dr. Lund said that, on the basis of these positive findings, music intervention as a sleep aid is now offered at Aalborg University Hospital to patients with depression-related insomnia.
 

Clinically meaningful?

Commenting on the findings, Gerald J. Haeffel, PhD, department of psychology, University of Notre Dame, South Bend, Ind., said that overall, the study showed there was a change in sleep-quality and quality of life scores of “about 10% in each.”

“This, on the surface, would seem to be a meaningful change,” although it is less clear whether it is “clinically meaningful.” Perhaps it is, “but it would be nice to have more information.”

It would be useful, he said, to “show the means for each group pre- to postintervention, along with standard deviations,” he added.

Dr. Haeffel added that on the basis of current results, it isn’t possible to determine whether individuals’ control over music choice is important.

“We have no idea if ‘choice’ or length of playlist had any causal role in the results. One would need to run a study with the same playlist, but in one group people have to listen to whatever song comes on versus another condition in which they get to choose a song off the same list,” he said.

He noted that his group conducted a study in which highly popular music that was chosen by individual participants was found to have a positive effect. Even so, he said, “we could not determine if it was ‘choice’ or ‘popularity’ that caused the positive effects of music.”

In addition, he said, the reason music has a positive effect on insomnia remains unclear.

“It is not because it helped with depression, and it’s not because it’s actually changing objective sleep parameters. It could be that it improves mood right before bed or helps distract people right before bed. At the same time, it could also just be a placebo effect,” said Dr. Haeffel.

In addition, he said, it’s important to note that the music intervention had no comparator, so “maybe just doing something different or getting to talk with researchers created the effect and has nothing to do with music.”

Overall, he believes that there are “not enough data” to use the sleep intervention that was employed in the current study “as primary intervention, but future work could show its usefulness as a supplement.”

Dr. Lund and Mr. Bertelsen reported ownership and sales of the MusicStar app. Dr. Haeffel reported no relevant financial relationships.

PARIS – Listening to music via curated playlists at bedtime is effective for depression-related insomnia, although the depression itself is unaffected, new research suggests.

The Music to Improve Sleep Quality in Adults With Depression and Insomnia (MUSTAFI) trial randomly assigned more than 110 outpatients with depression to either a music intervention or a waiting list. Sleep quality and quality of life significantly improved after listening to music for half an hour at bedtime for 4 weeks.

“This is a low-cost, safe intervention that has no side effects and may easily be implemented in psychiatry” along with existing treatments, lead researcher Helle Nystrup Lund, PhD, unit for depression, Aalborg (Denmark) University Hospital, said in an interview.

The findings were presented at the European Psychiatric Association 2023 Congress, and recently published in the Nordic Journal of Psychiatry.
 

Difficult to resolve

The researchers noted that insomnia is common in patients with depression and is “difficult to resolve.”

They noted that, while music is commonly used as a sleep aid and a growing evidence base suggests it has positive effects, there have been few investigations into the effectiveness of music for patients with depression-related insomnia.

To fill this research gap, 112 outpatients with depression and comorbid insomnia who were receiving care at a single center were randomly assigned to either an intervention group or a wait list control group.

Participants in the intervention group listened to music for a minimum of 30 minutes at bedtime for 4 weeks. The music was delivered via the MusicStar app, which is available as a free download from the Apple and Android (Google Play) app stores. The app was developed by Dr. Lund and Lars Rye Bertelsen, a PhD student and music therapist at Aalborg University Hospital.

The app is designed as a multicolored star, with each arm of the star linking to a playlist lasting between 30 minutes and 1 hour. Each color of the star indicates a different tempo of music.

Blue playlists, Dr. Lund explained, offer the quietest music, green is more lively, and red is the most dynamic. Gray playlists linked to project-related soundtracks, such as summer rain.

Dr. Lund said organizing the playlists by stimuli and color code, instead of genre, allows users to regulate their level of arousal and makes the music choice intuitive and easy.

She said that the genres of music include New Age, folk, pop, classical, and film soundtracks, “but no hard rock.”

“There’s actually a quite large selection of music available, because studies show that individual choice is important, as are personal preferences,” she said, adding that the endless choices offered by streaming services can cause confusion.

“So we made curated playlists and designed them with well-known pieces, but also with newly composed music not associated with anything,” Dr. Lund said.

Participants were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Hamilton Depression Rating Scale, and two World Health Organization well-being questionnaires (WHO-5, WHOQOL-BREF), as well as actigraphy.

Results showed that, at 4 weeks, participants in the intervention group experienced significant improvements in sleep quality in comparison with control persons. The effect size for the PSQI was –2.1, and for quality of life on the WHO-5, the effect size was 8.4.

A subanalysis revealed that the length of nocturnal sleep in the intervention group increased by an average of 18 minutes during the study from a baseline of approximately 5 hours per night, said Dr. Lund.

However, there were no changes in actigraphy measurements and no significant improvements in HAMD-17 scores.

Dr. Lund said that, on the basis of these positive findings, music intervention as a sleep aid is now offered at Aalborg University Hospital to patients with depression-related insomnia.
 

Clinically meaningful?

Commenting on the findings, Gerald J. Haeffel, PhD, department of psychology, University of Notre Dame, South Bend, Ind., said that overall, the study showed there was a change in sleep-quality and quality of life scores of “about 10% in each.”

“This, on the surface, would seem to be a meaningful change,” although it is less clear whether it is “clinically meaningful.” Perhaps it is, “but it would be nice to have more information.”

It would be useful, he said, to “show the means for each group pre- to postintervention, along with standard deviations,” he added.

Dr. Haeffel added that on the basis of current results, it isn’t possible to determine whether individuals’ control over music choice is important.

“We have no idea if ‘choice’ or length of playlist had any causal role in the results. One would need to run a study with the same playlist, but in one group people have to listen to whatever song comes on versus another condition in which they get to choose a song off the same list,” he said.

He noted that his group conducted a study in which highly popular music that was chosen by individual participants was found to have a positive effect. Even so, he said, “we could not determine if it was ‘choice’ or ‘popularity’ that caused the positive effects of music.”

In addition, he said, the reason music has a positive effect on insomnia remains unclear.

“It is not because it helped with depression, and it’s not because it’s actually changing objective sleep parameters. It could be that it improves mood right before bed or helps distract people right before bed. At the same time, it could also just be a placebo effect,” said Dr. Haeffel.

In addition, he said, it’s important to note that the music intervention had no comparator, so “maybe just doing something different or getting to talk with researchers created the effect and has nothing to do with music.”

Overall, he believes that there are “not enough data” to use the sleep intervention that was employed in the current study “as primary intervention, but future work could show its usefulness as a supplement.”

Dr. Lund and Mr. Bertelsen reported ownership and sales of the MusicStar app. Dr. Haeffel reported no relevant financial relationships.

People’s perception of time is subjective and based not only on their emotional state but also on heartbeat and heart rate (HR), two new studies suggest.

Researchers studied young adults with an electrocardiogram (ECG), measuring electrical activity at millisecond resolution while participants listened to tones that varied in duration. Participants were asked to report whether certain tones were longer or shorter, in relation to others.

The researchers found that the momentary perception of time was not continuous but rather expanded or contracted with each heartbeat. When the heartbeat preceding a tone was shorter, participants regarded the tone as longer in duration; but when the preceding heartbeat was longer, the participants experienced the tone as shorter.

“Our findings suggest that there is a unique role that cardiac dynamics play in the momentary experience of time,” lead author Saeedah Sadeghi, MSc, a doctoral candidate in the department of psychology at Cornell University, Ithaca, N.Y., said in an interview.

The study was published online  in Psychophysiology.

In a second study, published in the journal Current Biology, a separate team of researchers asked participants to judge whether a brief event – the presentation of a tone or an image – was shorter or longer than a reference duration. ECG was used to track systole and diastole when participants were presented with these events.

The researchers found that the durations were underestimated during systole and overestimated during diastole, suggesting that time seemed to “speed up” or “slow down,” based on cardiac contraction and relaxation. When participants rated the events as more arousing, their perceived durations contracted, even during diastole.

“In our new paper, we show that our heart shapes the perceived duration of events, so time passes quicker when the heart contracts but slower when the heart relaxes,” lead author Irena Arslanova, PhD, postdoctoral researcher in cognitive neuroscience, Royal Holloway University of London, told this news organization.
 

Temporal ‘wrinkles’

“Subjective time is malleable,” observed Ms. Sadeghi and colleagues in their report. “Rather than being a uniform dimension, perceived duration has ‘wrinkles,’ with certain intervals appearing to dilate or contract relative to objective time” – a phenomenon sometimes referred to as “distortion.”

“We have known that people aren’t always consistent in how they perceive time, and objective duration doesn’t always explain subjective perception of time,” Ms. Sadeghi said.

Although the potential role of the heart in the experience of time has been hypothesized, research into the heart-time connection has been limited, with previous studies focusing primarily on estimating the average cardiac measures on longer time scales over seconds to minutes.

The current study sought to investigate “the beat-by-beat fluctuations of the heart period on the experience of brief moments in time” because, compared with longer time scales, subsecond temporal perception “has different underlying mechanisms” and a subsecond stimulus can be a “small fraction of a heartbeat.”

To home in on this small fraction, the researchers studied 45 participants (aged 18-21), who listened to 210 tones ranging in duration from 80 ms (short) to 188 ms (long). The tones were linearly spaced at 18-ms increments (80, 98, 116, 134, 152, 170, 188).

Participants were asked to categorize each tone as “short” or “long.” All tones were randomly assigned to be synchronized either with the systolic or diastolic phase of the cardiac cycle (50% each). The tones were triggered by participants’ heartbeats.

In addition, participants engaged in a heartbeat-counting activity, in which they were asked not to touch their pulse but to count their heartbeats by tuning in to their bodily sensations at intervals of 25, 35, and 45 seconds.
 

‘Classical’ response

“Participants exhibited an increased heart period after tone onset, which returned to baseline following an average canonical bell shape,” the authors reported.

The researchers performed regression analyses to determine how, on average, the heart rate before the tone was related to perceived duration or how the amount of change after the tone was related to perceived duration.

They found that when the heart rate was higher before the tone, participants tended to be more accurate in their time perception. When the heartbeat preceding a tone was shorter, participants experienced the tone as longer; conversely, when the heartbeat was longer, they experienced the duration of the identical sound as shorter.

When participants focused their attention on the sounds, their heart rate was affected such that their orienting responses actually changed their heart rate and, in turn, their temporal perception.

“The orienting response is classical,” Ms. Sadeghi said. “When you attend to something unpredictable or novel, the act of orienting attention decreases the HR.”

She explained that the heartbeats are “noise to the brain.” When people need to perceive external events, “a decrease in HR facilitates the intake of things from outside and facilitates sensory intake.”

A lower HR “makes it easier for the person to take in the tone and perceive it, so it feels as though they perceive more of the tone and the duration seems longer – similarly, when the HR decreases.”

It is unknown whether this is a causal relationship, she cautioned, “but it seems as though the decrease in HR somehow makes it easier to ‘get’ more of the tone, which then appears to have longer duration.”
 

Bidirectional relationship

“We know that experienced time can be distorted,” said Dr. Arslanova. “Time flies by when we’re busy or having fun but drags on when we’re bored or waiting for something, yet we still don’t know how the brain gives rise to such elastic experience of time.”

The brain controls the heart in response to the information the heart provides about the state of the body, she noted, “but we have begun to see more research showing that the heart–brain relationship is bidirectional.”

This means that the heart plays a role in shaping “how we process information and experience emotions.” In this analysis, Dr. Arslanova and colleagues “wanted to study whether the heart also shapes the experience of time.”

To do so, they conducted two experiments.

In the first, participants (n = 28) were presented with brief events during systole or during diastole. The events took the form of an emotionally neutral visual shape or auditory tone, shown for durations of 200 to 400 ms.

Participants were asked whether these events were of longer or shorter duration, compared with a reference duration.

The researchers found significant main effect of cardiac phase systole (F(1,27) = 8.1, P =.01), with stimuli presented at diastole regarded, on average, as 7 ms longer than those presented at systole.

They also found a significant main effect of modality (F(1,27) = 5.7, P = .02), with tones judged, on average, as 13 ms longer than visual stimuli.

“This means that time ‘sped up’ during the heart’s contraction and ‘slowed down’ during the heart’s relaxation,” Dr. Arslanova said.

The effect of cardiac phase on duration perception was independent of changes in HR, the authors noted.

In the second experiment, participants performed a similar task, but this time, it involved the images of faces containing emotional expressions. The researchers again observed a similar pattern of time appearing to speed up during systole and slow down during diastole, with stimuli present at diastole regarded as being an average 9 ms longer than those presented at systole.

These opposing effects of systole and diastole on time perception were present only for low and average arousal ratings (b = 14.4 [SE 3.2], P < .001 and b = 9.2 [2.3], P <.001, respectively). However, this effect disappeared when arousal ratings increased (b = 4.1 [3.2] P =.21).

“Interestingly, when participants rated the events as more arousing, their perceived durations contracted, even during the heart’s relaxation,” Dr. Arslanova observed. “This means that in a nonaroused state, the two cardiac phases pull the experienced duration in opposite directions – time contracts, then expands.”

The findings “also predict that increasing HR would speed up passing time, making events seem shorter, because there will be a stronger influence from the heart’s contractions,” she said.

She described the relationship between time perception and emotion as complex, noting that the findings are important because they show “that the way we experience time cannot be examined in isolation from our body,” she said.
 

Converging evidence

Martin Wiener, PhD, assistant professor, George Mason University, Fairfax, Va., said both papers “provide converging evidence on the role of the heart in our perception of time.”

Together, “the results share that our sense of time – that is, our incoming sensory perception of the present ‘moment’ – is adjusted or ‘gated’ by both our HR and cardiac phase,” said Dr. Wiener, executive director of the Timing Research Forum.

The studies “provide a link between the body and the brain, in terms of our perception, and that we cannot study one without the context of the other,” said Dr. Wiener, who was not involved with the current study.

“All of this opens up a new avenue of research, and so it is very exciting to see,” Dr. Wiener stated.

No source of funding was listed for the study by Ms. Sadeghi and coauthors. They declared no relevant financial relationships.

Dr. Arslanova and coauthors declared no competing interests. Senior author Manos Tsakiris, PhD, receives funding from the European Research Council Consolidator Grant. Dr. Wiener declared no relevant financial relationships.
 

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

People’s perception of time is subjective and based not only on their emotional state but also on heartbeat and heart rate (HR), two new studies suggest.

Researchers studied young adults with an electrocardiogram (ECG), measuring electrical activity at millisecond resolution while participants listened to tones that varied in duration. Participants were asked to report whether certain tones were longer or shorter, in relation to others.

The researchers found that the momentary perception of time was not continuous but rather expanded or contracted with each heartbeat. When the heartbeat preceding a tone was shorter, participants regarded the tone as longer in duration; but when the preceding heartbeat was longer, the participants experienced the tone as shorter.

“Our findings suggest that there is a unique role that cardiac dynamics play in the momentary experience of time,” lead author Saeedah Sadeghi, MSc, a doctoral candidate in the department of psychology at Cornell University, Ithaca, N.Y., said in an interview.

The study was published online  in Psychophysiology.

In a second study, published in the journal Current Biology, a separate team of researchers asked participants to judge whether a brief event – the presentation of a tone or an image – was shorter or longer than a reference duration. ECG was used to track systole and diastole when participants were presented with these events.

The researchers found that the durations were underestimated during systole and overestimated during diastole, suggesting that time seemed to “speed up” or “slow down,” based on cardiac contraction and relaxation. When participants rated the events as more arousing, their perceived durations contracted, even during diastole.

“In our new paper, we show that our heart shapes the perceived duration of events, so time passes quicker when the heart contracts but slower when the heart relaxes,” lead author Irena Arslanova, PhD, postdoctoral researcher in cognitive neuroscience, Royal Holloway University of London, told this news organization.
 

Temporal ‘wrinkles’

“Subjective time is malleable,” observed Ms. Sadeghi and colleagues in their report. “Rather than being a uniform dimension, perceived duration has ‘wrinkles,’ with certain intervals appearing to dilate or contract relative to objective time” – a phenomenon sometimes referred to as “distortion.”

“We have known that people aren’t always consistent in how they perceive time, and objective duration doesn’t always explain subjective perception of time,” Ms. Sadeghi said.

Although the potential role of the heart in the experience of time has been hypothesized, research into the heart-time connection has been limited, with previous studies focusing primarily on estimating the average cardiac measures on longer time scales over seconds to minutes.

The current study sought to investigate “the beat-by-beat fluctuations of the heart period on the experience of brief moments in time” because, compared with longer time scales, subsecond temporal perception “has different underlying mechanisms” and a subsecond stimulus can be a “small fraction of a heartbeat.”

To home in on this small fraction, the researchers studied 45 participants (aged 18-21), who listened to 210 tones ranging in duration from 80 ms (short) to 188 ms (long). The tones were linearly spaced at 18-ms increments (80, 98, 116, 134, 152, 170, 188).

Participants were asked to categorize each tone as “short” or “long.” All tones were randomly assigned to be synchronized either with the systolic or diastolic phase of the cardiac cycle (50% each). The tones were triggered by participants’ heartbeats.

In addition, participants engaged in a heartbeat-counting activity, in which they were asked not to touch their pulse but to count their heartbeats by tuning in to their bodily sensations at intervals of 25, 35, and 45 seconds.
 

‘Classical’ response

“Participants exhibited an increased heart period after tone onset, which returned to baseline following an average canonical bell shape,” the authors reported.

The researchers performed regression analyses to determine how, on average, the heart rate before the tone was related to perceived duration or how the amount of change after the tone was related to perceived duration.

They found that when the heart rate was higher before the tone, participants tended to be more accurate in their time perception. When the heartbeat preceding a tone was shorter, participants experienced the tone as longer; conversely, when the heartbeat was longer, they experienced the duration of the identical sound as shorter.

When participants focused their attention on the sounds, their heart rate was affected such that their orienting responses actually changed their heart rate and, in turn, their temporal perception.

“The orienting response is classical,” Ms. Sadeghi said. “When you attend to something unpredictable or novel, the act of orienting attention decreases the HR.”

She explained that the heartbeats are “noise to the brain.” When people need to perceive external events, “a decrease in HR facilitates the intake of things from outside and facilitates sensory intake.”

A lower HR “makes it easier for the person to take in the tone and perceive it, so it feels as though they perceive more of the tone and the duration seems longer – similarly, when the HR decreases.”

It is unknown whether this is a causal relationship, she cautioned, “but it seems as though the decrease in HR somehow makes it easier to ‘get’ more of the tone, which then appears to have longer duration.”
 

Bidirectional relationship

“We know that experienced time can be distorted,” said Dr. Arslanova. “Time flies by when we’re busy or having fun but drags on when we’re bored or waiting for something, yet we still don’t know how the brain gives rise to such elastic experience of time.”

The brain controls the heart in response to the information the heart provides about the state of the body, she noted, “but we have begun to see more research showing that the heart–brain relationship is bidirectional.”

This means that the heart plays a role in shaping “how we process information and experience emotions.” In this analysis, Dr. Arslanova and colleagues “wanted to study whether the heart also shapes the experience of time.”

To do so, they conducted two experiments.

In the first, participants (n = 28) were presented with brief events during systole or during diastole. The events took the form of an emotionally neutral visual shape or auditory tone, shown for durations of 200 to 400 ms.

Participants were asked whether these events were of longer or shorter duration, compared with a reference duration.

The researchers found significant main effect of cardiac phase systole (F(1,27) = 8.1, P =.01), with stimuli presented at diastole regarded, on average, as 7 ms longer than those presented at systole.

They also found a significant main effect of modality (F(1,27) = 5.7, P = .02), with tones judged, on average, as 13 ms longer than visual stimuli.

“This means that time ‘sped up’ during the heart’s contraction and ‘slowed down’ during the heart’s relaxation,” Dr. Arslanova said.

The effect of cardiac phase on duration perception was independent of changes in HR, the authors noted.

In the second experiment, participants performed a similar task, but this time, it involved the images of faces containing emotional expressions. The researchers again observed a similar pattern of time appearing to speed up during systole and slow down during diastole, with stimuli present at diastole regarded as being an average 9 ms longer than those presented at systole.

These opposing effects of systole and diastole on time perception were present only for low and average arousal ratings (b = 14.4 [SE 3.2], P < .001 and b = 9.2 [2.3], P <.001, respectively). However, this effect disappeared when arousal ratings increased (b = 4.1 [3.2] P =.21).

“Interestingly, when participants rated the events as more arousing, their perceived durations contracted, even during the heart’s relaxation,” Dr. Arslanova observed. “This means that in a nonaroused state, the two cardiac phases pull the experienced duration in opposite directions – time contracts, then expands.”

The findings “also predict that increasing HR would speed up passing time, making events seem shorter, because there will be a stronger influence from the heart’s contractions,” she said.

She described the relationship between time perception and emotion as complex, noting that the findings are important because they show “that the way we experience time cannot be examined in isolation from our body,” she said.
 

Converging evidence

Martin Wiener, PhD, assistant professor, George Mason University, Fairfax, Va., said both papers “provide converging evidence on the role of the heart in our perception of time.”

Together, “the results share that our sense of time – that is, our incoming sensory perception of the present ‘moment’ – is adjusted or ‘gated’ by both our HR and cardiac phase,” said Dr. Wiener, executive director of the Timing Research Forum.

The studies “provide a link between the body and the brain, in terms of our perception, and that we cannot study one without the context of the other,” said Dr. Wiener, who was not involved with the current study.

“All of this opens up a new avenue of research, and so it is very exciting to see,” Dr. Wiener stated.

No source of funding was listed for the study by Ms. Sadeghi and coauthors. They declared no relevant financial relationships.

Dr. Arslanova and coauthors declared no competing interests. Senior author Manos Tsakiris, PhD, receives funding from the European Research Council Consolidator Grant. Dr. Wiener declared no relevant financial relationships.
 

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

People’s perception of time is subjective and based not only on their emotional state but also on heartbeat and heart rate (HR), two new studies suggest.

Researchers studied young adults with an electrocardiogram (ECG), measuring electrical activity at millisecond resolution while participants listened to tones that varied in duration. Participants were asked to report whether certain tones were longer or shorter, in relation to others.

The researchers found that the momentary perception of time was not continuous but rather expanded or contracted with each heartbeat. When the heartbeat preceding a tone was shorter, participants regarded the tone as longer in duration; but when the preceding heartbeat was longer, the participants experienced the tone as shorter.

“Our findings suggest that there is a unique role that cardiac dynamics play in the momentary experience of time,” lead author Saeedah Sadeghi, MSc, a doctoral candidate in the department of psychology at Cornell University, Ithaca, N.Y., said in an interview.

The study was published online  in Psychophysiology.

In a second study, published in the journal Current Biology, a separate team of researchers asked participants to judge whether a brief event – the presentation of a tone or an image – was shorter or longer than a reference duration. ECG was used to track systole and diastole when participants were presented with these events.

The researchers found that the durations were underestimated during systole and overestimated during diastole, suggesting that time seemed to “speed up” or “slow down,” based on cardiac contraction and relaxation. When participants rated the events as more arousing, their perceived durations contracted, even during diastole.

“In our new paper, we show that our heart shapes the perceived duration of events, so time passes quicker when the heart contracts but slower when the heart relaxes,” lead author Irena Arslanova, PhD, postdoctoral researcher in cognitive neuroscience, Royal Holloway University of London, told this news organization.
 

Temporal ‘wrinkles’

“Subjective time is malleable,” observed Ms. Sadeghi and colleagues in their report. “Rather than being a uniform dimension, perceived duration has ‘wrinkles,’ with certain intervals appearing to dilate or contract relative to objective time” – a phenomenon sometimes referred to as “distortion.”

“We have known that people aren’t always consistent in how they perceive time, and objective duration doesn’t always explain subjective perception of time,” Ms. Sadeghi said.

Although the potential role of the heart in the experience of time has been hypothesized, research into the heart-time connection has been limited, with previous studies focusing primarily on estimating the average cardiac measures on longer time scales over seconds to minutes.

The current study sought to investigate “the beat-by-beat fluctuations of the heart period on the experience of brief moments in time” because, compared with longer time scales, subsecond temporal perception “has different underlying mechanisms” and a subsecond stimulus can be a “small fraction of a heartbeat.”

To home in on this small fraction, the researchers studied 45 participants (aged 18-21), who listened to 210 tones ranging in duration from 80 ms (short) to 188 ms (long). The tones were linearly spaced at 18-ms increments (80, 98, 116, 134, 152, 170, 188).

Participants were asked to categorize each tone as “short” or “long.” All tones were randomly assigned to be synchronized either with the systolic or diastolic phase of the cardiac cycle (50% each). The tones were triggered by participants’ heartbeats.

In addition, participants engaged in a heartbeat-counting activity, in which they were asked not to touch their pulse but to count their heartbeats by tuning in to their bodily sensations at intervals of 25, 35, and 45 seconds.
 

‘Classical’ response

“Participants exhibited an increased heart period after tone onset, which returned to baseline following an average canonical bell shape,” the authors reported.

The researchers performed regression analyses to determine how, on average, the heart rate before the tone was related to perceived duration or how the amount of change after the tone was related to perceived duration.

They found that when the heart rate was higher before the tone, participants tended to be more accurate in their time perception. When the heartbeat preceding a tone was shorter, participants experienced the tone as longer; conversely, when the heartbeat was longer, they experienced the duration of the identical sound as shorter.

When participants focused their attention on the sounds, their heart rate was affected such that their orienting responses actually changed their heart rate and, in turn, their temporal perception.

“The orienting response is classical,” Ms. Sadeghi said. “When you attend to something unpredictable or novel, the act of orienting attention decreases the HR.”

She explained that the heartbeats are “noise to the brain.” When people need to perceive external events, “a decrease in HR facilitates the intake of things from outside and facilitates sensory intake.”

A lower HR “makes it easier for the person to take in the tone and perceive it, so it feels as though they perceive more of the tone and the duration seems longer – similarly, when the HR decreases.”

It is unknown whether this is a causal relationship, she cautioned, “but it seems as though the decrease in HR somehow makes it easier to ‘get’ more of the tone, which then appears to have longer duration.”
 

Bidirectional relationship

“We know that experienced time can be distorted,” said Dr. Arslanova. “Time flies by when we’re busy or having fun but drags on when we’re bored or waiting for something, yet we still don’t know how the brain gives rise to such elastic experience of time.”

The brain controls the heart in response to the information the heart provides about the state of the body, she noted, “but we have begun to see more research showing that the heart–brain relationship is bidirectional.”

This means that the heart plays a role in shaping “how we process information and experience emotions.” In this analysis, Dr. Arslanova and colleagues “wanted to study whether the heart also shapes the experience of time.”

To do so, they conducted two experiments.

In the first, participants (n = 28) were presented with brief events during systole or during diastole. The events took the form of an emotionally neutral visual shape or auditory tone, shown for durations of 200 to 400 ms.

Participants were asked whether these events were of longer or shorter duration, compared with a reference duration.

The researchers found significant main effect of cardiac phase systole (F(1,27) = 8.1, P =.01), with stimuli presented at diastole regarded, on average, as 7 ms longer than those presented at systole.

They also found a significant main effect of modality (F(1,27) = 5.7, P = .02), with tones judged, on average, as 13 ms longer than visual stimuli.

“This means that time ‘sped up’ during the heart’s contraction and ‘slowed down’ during the heart’s relaxation,” Dr. Arslanova said.

The effect of cardiac phase on duration perception was independent of changes in HR, the authors noted.

In the second experiment, participants performed a similar task, but this time, it involved the images of faces containing emotional expressions. The researchers again observed a similar pattern of time appearing to speed up during systole and slow down during diastole, with stimuli present at diastole regarded as being an average 9 ms longer than those presented at systole.

These opposing effects of systole and diastole on time perception were present only for low and average arousal ratings (b = 14.4 [SE 3.2], P < .001 and b = 9.2 [2.3], P <.001, respectively). However, this effect disappeared when arousal ratings increased (b = 4.1 [3.2] P =.21).

“Interestingly, when participants rated the events as more arousing, their perceived durations contracted, even during the heart’s relaxation,” Dr. Arslanova observed. “This means that in a nonaroused state, the two cardiac phases pull the experienced duration in opposite directions – time contracts, then expands.”

The findings “also predict that increasing HR would speed up passing time, making events seem shorter, because there will be a stronger influence from the heart’s contractions,” she said.

She described the relationship between time perception and emotion as complex, noting that the findings are important because they show “that the way we experience time cannot be examined in isolation from our body,” she said.
 

Converging evidence

Martin Wiener, PhD, assistant professor, George Mason University, Fairfax, Va., said both papers “provide converging evidence on the role of the heart in our perception of time.”

Together, “the results share that our sense of time – that is, our incoming sensory perception of the present ‘moment’ – is adjusted or ‘gated’ by both our HR and cardiac phase,” said Dr. Wiener, executive director of the Timing Research Forum.

The studies “provide a link between the body and the brain, in terms of our perception, and that we cannot study one without the context of the other,” said Dr. Wiener, who was not involved with the current study.

“All of this opens up a new avenue of research, and so it is very exciting to see,” Dr. Wiener stated.

No source of funding was listed for the study by Ms. Sadeghi and coauthors. They declared no relevant financial relationships.

Dr. Arslanova and coauthors declared no competing interests. Senior author Manos Tsakiris, PhD, receives funding from the European Research Council Consolidator Grant. Dr. Wiener declared no relevant financial relationships.
 

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

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.