Search

Bipolar disorder is characterized by recurrent mood episodes, affecting 1% to 2% of the population. Although its defining features are manic and hypomanic episodes, its course is dominated by depressive syndromes. Diagnosis can be challenging owing to symptom overlap with other disorders. Management goals include early and complete remission of acute episodes and the prevention of relapse between episodes. We present an overview of bipolar disorder and its subtypes, including algorithms and suggestions for screening, assessment, and treatment.

Sex is seldom considered as a potential moderator of the impact of bipolar disorder (BD) on cardiovascular disease (CVD) risk. We aimed to characterize the sex-specific association of CVD and BD using data from the UK Biobank.In a cross-sectional analysis, we compared the odds ratio between women and men with BD for seven CVD diagnoses (coronary artery disease, myocardial infarction, angina, atrial fibrillation, heart failure, stroke, and essential hypertension) and four cardiovascular biomarkers (arterial stiffness index, low-density lipoprotein, C-reactive protein, and HbA1c) in 293 participants with BD and 257,380 psychiatrically healthy controls in the UK Biobank.After adjusting for age, we found a two- to three-fold stronger association among women than among men between BD and rates of coronary artery disease, heart failure, and essential hypertension, with a significant sex-by-diagnosis interactions. The association remained significant after controlling for self-reported race, education, income, and smoking status. After controlling for potential confounders, there was no significant association between sex and any cardiovascular biomarkers.These analyses could not disentangle effects of BD from its treatment.Our results underscore the importance of incorporating sex and mental illness in risk estimation tools for CVD, and improving screening for, and timely treatment of, CVD in those with BD. Future research is needed to better understand the contributors and mechanisms of sex differences related to CVD risk in BD.

BackgroundThe neural underpinnings of bipolar disorder (BD) remain poorly understood. The cerebellum is ideally positioned to modulate emotional regulation circuitry yet has been understudied in BD. Previous studies have suggested differences in cerebellar activity and metabolism in BD, however findings on cerebellar structural differences remain contradictory.MethodsWe collected 3T anatomical MRI scans from participants with (N = 131) and without (N = 81) BD type I. Differences in cerebellar volumes were assessed along with factors that influence the results.ResultsThe cerebellar cortex was smaller bilaterally in participants with BD. Polygenic propensity score (bipolar N = 103, control N = 64) did not predict any cerebellar volumes, suggesting that non-genetic factors may have greater influence on the cerebellar volume difference we observed in BD. Cerebellar white matter volumes increased with more adverse childhood events, but we did not observe any associations with parental psychiatric illness. We also evaluated time from onset and symptom burden and found no associations with cerebellar volumes, suggesting neurodevelopment may differ prior to onset. Finally, we found taking sedatives was associated with larger cerebellar white matter and non-significantly larger cortical volume.LimitationsThis study was cross-sectional, limiting interpretation of possible mechanisms. Most of our participants were White, which could limit the generalizability. Additionally, we did not account for potential polypharmacy interactions.ConclusionsThese findings suggest that external influences, such as medications, may influence cerebellum structure in BD and may mask underlying differences. Accounting for medication may be critical for consistent findings in future studies.

AIMS: Bipolar type I disorder (BD) is characterized by severe mood swings and occurs in about 1% of the population. The mechanisms underlying the disorder remain unknown. Prior studies have suggested abnormalities in brain metabolism using (1)H and (31)P magnetic resonance spectroscopy (MRS). Supporting altered metabolism, in previous studies we found T1ρ relaxation times in the cerebellum were elevated in participants with BD. In addition, T1ρ relaxation times in the basal ganglia were lower in participants with BD experiencing depressed mood. Based on these findings, this study sought to probe brain metabolism with a focus of extending these assessments to the cerebellum. METHODS: This study collected data from 64 participants with Bipolar type I disorder (BD) and 42 controls. Subjects were scanned at both 3T (anatomical, functional, and T1ρ imaging data) and 7T ((31)P and (1)H spectroscopy). Regions of interest defined by the 1H MRS data were used to explore metabolic and functional changes in the cerebellar vermis and putamen. RESULTS: Elevated concentrations of n-Acetyl-L-aspartate (NAA), glutamate, glutathione, taurine, and creatine were found in the cerebellar vermis along with decreased intra-cellular pH. Similar trends were observed in the right putamen for glutamate, creatine, and pH. We also observed a relationship between T1ρ relaxation times and mood in the putamen. We did not observe a significant effect of medications on these measures. LIMITATIONS: The study was cross sectional in design and employed a naturalistic approach for assessing the impact of medications on the results. CONCLUSION: This study supports prior findings of reduced pH in mitochondrial dysfunction in BD while also showing that these differences extend to the cerebellum.

Background The ability to predict an individual's risk of mood episode recurrence can facilitate personalized medicine in bipolar disorder (BD). We sought to externally validate, in an adult sample, a risk calculator of mood episode recurrence developed in youth/young adults with BD from the Course and Outcome of Bipolar Youth (COBY) study. Methods Adult participants from the National Institute of Mental Health Collaborative Depression Study (CDS; N=258; mean(SD) age=35.5(12.0) years; mean follow-up=24.9 years) were utilized as a sample to validate the youth COBY risk calculator for onset of depressive, manic, or any mood episodes. Results In this older validation sample, the risk calculator predicted recurrence of any episode over 1, 2, 3, or 5-year follow-up intervals, with Area Under the Curves (AUCs) approximating 0.77. The AUC for prediction of depressive episodes was about 0.81 for each of the time windows, which was higher than for manic or hypomanic episodes (AUC=0.72). While the risk calculator was well-calibrated across the range of risk scores, it systematically underestimated risk in the CDS sample by about 20%. The length of current remission was a highly significant predictor of recurrence risk in the CDS sample. Limitations Predominantly self-reported White samples may limit generalizability; the risk calculator does not assess more proximal risk (e.g., 1 month). Conclusions Risk of mood episode recurrence can be predicted with good accuracy in youth and adults with BD in remission. The risk calculators may help identify higher risk BD subgroups for treatment and research.

Objective Acceptance and Commitment Therapy (ACT) is a behavioral intervention demonstrating sustained improvements in anxiety in individuals with chronic anxiety and psychological distress. Because anxiety disorders are associated with the development of cardiovascular disease (CVD), we hypothesized that a novel 1-day ACT workshop would both lower anxiety and improve vascular function in persons with moderate/high anxiety. Methods In a randomized controlled study, 72 adults (age 33.9 ± 8.6 (SD) years) with baseline moderate/high anxiety completed a one-day ACT intervention (n = 44, age 33.9 ± 8.7 years) or control (n = 28, age 37.1 ± 10.1 years). Pre-specified secondary outcomes were measured over 12 weeks: aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]), forearm vascular endothelial function (post-ischemic peak forearm blood flow [FBF] via plethysmography), and brachial artery flow-mediated dilation (FMD). Carotid artery stiffness (β-stiffness index), and inflammatory markers (C-reactive protein and tumor necrosis factor-alpha) were also explored. Results Although the intervention had a significant and sustained effect on the primary outcome of anxiety as measured by the Beck Anxiety Inventory, the 1-day ACT workshop was not associated with improvement in vascular or inflammatory endpoints. The intervention was unexpectedly associated with increases in β-stiffness index that were also associated with changing trait anxiety. Conclusion Anxiety improvements did not translate into improvements in any of the vascular function outcomes. This may reflect a less-than-robust effect of the intervention on anxiety, failure in design to select those with vascular dysfunction, or not intervening on a relevant causal pathway. (Trial registration NCT02915874 at www.clinicaltrials.gov ).

Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n=50), BD individuals with (n=77, BD/SA) and without (n=67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n=48) and BD/non-SA (n=47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F=5.424,p=0.005), with the highest GrimAgeAccel in BD/SA (p=0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p=0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.

INTRODUCTION: Despite the high risk for suicide, relatively few studies have explored the relationship between suicide and brain imaging measures in bipolar disorder. In addition, fewer studies have explored the possibility that altered brain metabolism may be associated with suicide attempt. To begin to fill in these gaps, we evaluated functional (task based fMRI) and metabolic (quantitative T1ρ) differences associated with suicide attempt in participants with bipolar disorder. METHODS: Thirty-nine participants with bipolar disorder underwent fMRI during a flashing checkerboard task and 27 also underwent quantitative T1ρ. The relationship between neuroimaging and history of suicide attempt was tested using multiple regression while adjusting for age, sex, and current mood state. Differences between two measures of suicide attempt (binary: yes/no and continuous: number of attempts) were quantified using the corrected Akaike Information Criterion. RESULTS: Participants who had attempted suicide had greater fMRI task-related activation in visual areas and the cerebellum. The number of suicide attempts was associated with a difference in BOLD response in the amygdala, prefrontal cortex, and cerebellum. Increased quantitative T1ρ was associated with number of suicide attempts in limbic, basal ganglia, and prefrontal cortex regions. LIMITATIONS: This study is a secondary analysis with a modest sample size. Differences between measures of suicide history may be due to differences in statistical power. CONCLUSIONS: History of suicide was associated with limbic, prefrontal, and cerebellar alterations. Results comparing those with and without suicide attempts differed from results using number of suicide attempts, suggesting that these variables have different neurobiological underpinnings.

OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth.METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer.RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001).CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.

Background : It has not been established that suicide risk with mixed symptoms is any greater than the depressive component or if there is synergy between depressive and manic symptoms in conveying suicide risk. Methods : The National Network of Depression Centers Mood Outcomes Program collected data from measurement-based care for 17,179 visits from 6,105 unique individuals with clinically diagnosed mood disorders (998 bipolar disorder, 5,117 major depression). The Patient Health Questionaire-8 (PHQ-8) captured depressive symptoms and the Altman Self-Rating Mania scale (ASRM) measured hypomanic/manic symptoms. Generalized linear mixed models assessed associations between depressive symptoms, manic symptoms, and their interaction (to test for synergistic effects of mixed symptoms) on the primary outcome of suicidal ideation or behavior (secondarily suicidal behavior only) from the Columbia-Suicide Severity Rating Scale (C-SSRS). Moderation was assessed. Results : PHQ-8 scores were strongly associated with suicide-related outcomes across diagnoses. ASRM scores showed no association with suicidal ideation/behavior in bipolar disorder and an inverse association in major depression. There was no evidence of synergy between depressive and manic symptoms. There was no moderation by sex, race, or mood disorder polarity. Those over 55 years of age showed a protective effect of manic symptoms, which was lost when depressive symptoms were also present (mixed symptoms). Discussion : Mixed depressive and manic symptoms convey no excess risk of suicidal ideation or behavior beyond the risk conveyed by the depressive symptoms alone. Depressive symptoms are strongly linked to suicidal ideation and suicidal behavior and represent an important and potentially modifiable risk factor for suicide.

Posterior fossa arachnoid cysts (PFACs) are rare congenital abnormalities observed in 0.3 to 1.7% of the population and are traditionally thought to be benign. While conducting a neuroimaging study investigating cerebellar structure in bipolar disorder, we observed a higher incidence of PFACs in bipolar patients (5 of 75; 6.6%) compared to the neuronormative control group (1 of 54; 1.8%). In this report, we detail the cases of the five patients with bipolar disorder who presented with PFACs. Additionally, we compare neuropsychiatric measures and cerebellar volumes of these patients to neuronormative controls and bipolar controls (those with bipolar disorder without neuroanatomical abnormalities). Our findings suggest that patients with bipolar disorder who also present with PFACs may have a milder symptom constellation relative to patients with bipolar disorder and no neuroanatomical abnormalities. Furthermore, our observations align with prior literature suggesting an association between PFACs and psychiatric symptoms that warrants further study. While acknowledging sample size limitations, our primary aim in the present work is to highlight a connection between PFACs and BD-associated symptoms and encourage further study of cerebellar abnormalities in psychiatry.

Background Recruitment to psychiatry as a career has been challenging in Canada and abroad despite the known shortage and increasing burden of psychiatric issues globally. Deterrents to choosing psychiatry as a career include its negative stigma and paucity of knowledge about the field. The study goal was to evaluate the Ottawa Psychiatry Enrichment Program (OPEP), a one-week extracurricular program about psychiatry as a career for 1st and 2nd year medical students. We hypothesized OPEP would improve students’ attitudes towards psychiatry, and positive changes would be sustained 2–3 years later following their residency match. We hypothesized there would be a high recruitment of OPEP attendees to psychiatry programs. Methods 1st and 2nd year medical students from Canada applied to OPEP. Attendees completed the Attitudes Towards Psychiatry Questionnaire (ATP-30) at three times: before OPEP (PreOPEP), after OPEP (PostOPEP) and after their Canadian Residency Matching Service (CaRMs) match 2–3 years later. OPEP ATP-30 scores were compared to third-year student ATP-30 scores before and after their psychiatry rotation. Data were analysed using Friedman non-parametric ANOVA and post hoc testing by either Wilcoxon rank sum test, Wilcoxon matched pairs signed rank test, or parametric Welch independent t-test as appropriate. Effect sizes of group mean differences were calculated using Cohen’s “d”. Results Between 2017–2018, 29/53 Canadian applicants were selected for OPEP. 100%, 93.1% and 75.8% of OPEP students completed the PreOPEP, PostOPEP, and CaRMs ATP-30 surveys respectively. 43% of OPEP attendees matched to psychiatry. PostOPEP ATP-30 scores (mean = 133, median = 137, SD = 10.6) were significantly higher than PreOPEP ATP-30 (mean score = 121, median = 122, SD = 9.3, p p p = 0.078, d = 0.44). 97/202 students completed the ATP-30 before and after their psychiatry rotation (clerkship). Clerkship effect size on improvement in ATP-30 was moderate (d = 0.39). There was a non-significant difference between OPEP CaRMS ATP-30 and post clerkship ATP-30 scores (median 127 vs 121, p = 0.056). Conclusions OPEP ameliorated attitudes toward Psychiatry, but improvement deteriorated longitudinally. Strategies for program design, and innovations to boost/retain improvements during clerkship years are discussed.

Studies have shown that chronic obstructive pulmonary disease (COPD) and smoking are associated with increased suicide risk. To date there are no prospective studies examining suicide risk among smokers along a spectrum of pulmonary disease ranging from completely normal spirometry to severe COPD.Which clinical variables predict death by suicide or overdose of indeterminate intent in a large cohort of heavy smokers within the COPDGene study?We studied data from 9,930 participants involved in COPDGene, a multisite, prospective cohort study of current and former smokers. Primary cause of adjudicated deaths was identified using death certificates, family reports, and medical records. We examined time to death by suicide/overdose as the primary outcome in Cox regression adjusted for age, sex, race, BMI, pack-years, current smoking status, airflow limitation (%predicted FEVThe cohort was 47% female, 33% Black (67% White), had a mean (SD) age of 59.6 (9.0) years, and mean FEVIn this well-characterized cohort of current and former smokers with and without COPD, we identified risk factors for suicide/overdose that emphasize the subjective experience of illness over objective assessments of lung function.

OBJECTIVE: People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population.METHODS: Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age).RESULTS: Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES).CONCLUSIONS: Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.

The authors describe how attitudes and confidence in the integration of psychiatry into other areas of medicine change over time during clinical clerkship in medical school.From January 2015 to December 2016, medical students from the University of Iowa were recruited for a prospective study of changes in the Attitudes and Confidence in the Integration of Psychiatry Scale (ACIP) scale. The survey instrument was completed before their psychiatry clerkship, after the clerkship, and at the end of the year following that and other clinical clerkships. Other information such as gender, time spent in clerkship, USMLE Step 1 score, and clerkship grades was also collected.A total of 172 surveys were completed by 138 students. The ACIP score was significantly higher at the end of the participants' clinical clerkship (67.2 to 76.6; t=-7.72, p0.0001). Of the two ACIP subscales, confidence increased significantly (25.6 to 33.3; t=-9.82, p0.0001), but attitudes toward integration of psychiatry did not (41.7 to 43.4; t=-1.96, p=0.059). Similar findings were seen in the subset of 34 students for whom pre- and post-clerkship data could be matched.At the end of their clinical clerkship, medical students feel more confident providing psychiatric care. The lack of significant increase in the ACIP scale's attitude subscale either demonstrates that attitude scores going into clerkship were already high and did not deteriorate, or highlights an area for clerkship curriculum development.

Weight gain is a common side-effect of medications used to treat major depressive disorder (MDD). We sought to estimate the frequency of weight gain for obesogenic medications prescribed for MDD and to evaluate if bupropion mitigated risk for weight gain. We analyzed a prospective cohort of patients with weight available at baseline and 12 weeks (n = 1,032) or 24 weeks (n = 871) in a post hoc analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) study of patients with MDD who failed at least one medication trial. We compared weight gain between those on versus not on medications with high risk for weight gain, including a subgroup receiving combination treatment with bupropion. A second analysis evaluated weight gain across traditional medication classes, adjusting for potential confounding variables. Those on medications identified as high risk for weight gain were significantly more likely to experience clinically significant weight gain (≥3%) at 12 weeks (29.3% vs. 16.3%, p < .001) and 24 weeks (33.5% vs. 23.5%, p = .015). No protection from clinically significant weight gain was observed among patients treated with a high-risk medication concomitantly with bupropion (N = 31, 35% and 52% with clinically significant weight gain at 12 and 24 weeks). Antipsychotic medications and tricyclic antidepressants were most often associated with clinically significant weight gain. This study helps quantify the real-world risk of weight gain for patients with MDD on medications with high risk for weight gain, especially for patients taking antipsychotics. Concurrent treatment with bupropion does not appear to mitigate the weight gain risk.

BACKGROUND Cognitive-behavioral therapies often are recommended for anxiety disorders. However, treatment adherence and compliance are major barriers for these treatments, which are often delivered in 10 to 12 sessions over several months. This randomized controlled trial (trial registration NCT02915874 at www.clinicaltrials.gov) examined the effectiveness and feasibility of a 1-day cognitive-behavioral intervention for mixed anxiety. METHODS A total of 72 adults with moderate-to-high anxiety were randomized into a 1-day acceptance and commitment therapy (ACT) work-shop (n = 44) or treatment as usual (n = 28). Follow-up assessments were conducted 6 and 12 weeks after the workshop. Clinical outcomes were anxiety (primary) and depressive (secondary) symptoms, as measured by the Beck Anxiety Inventory and Beck Depression Inventory-II, respectively. Proposed mediators of ACT-psychological flexibility and commit-ted action-also were examined. RESULTS Participants assigned to the ACT workshop showed significant improvements in anxiety (beta = -1.13; P = .02) and depression (beta = -1.09; P = .02) after 12 weeks. Consistent with the theoretical model, these clinical improvements were mediated by psychological flexibility and committed action. Notable limitations included the sample size, inability to blind to treatment condition, and a racially and ethnically homogeneous sample. CONCLUSIONS Our 1-day ACT workshop was effective for anxiety with co-occurring depressive symptoms. One-day interventions are a promising alternative to weekly treatments.

Objective: This study used meta-analysis to assess disparities in cardiovascular disease (CVD) screening and treatment in people with mental disorders, a group that has elevated CVD incidence and mortality.Methods: The authors searched PubMed and PsycInfo through July 31, 2020, and conducted a random-effect meta-analysis of observational studies comparing CVD screening and treatment in people with and without mental disorders. The primary outcome was odds ratios for CVD screening and treatment. Sensitivity analyses on screening and treatment separately and on specific procedures, subgroup analyses by country, and by controlling for confounding by indication, as well as meta-regressions, were also run, and publication bias and quality were assessed.Results: Forty-seven studies (N=24,400,452 patients, of whom 1,283,602 had mental disorders) from North America (k=26), Europe (k=16), Asia (k=4), and Australia (k=1) were meta-analyzed. Lower rates of screening or treatment in patients with mental disorders emerged for any CVD (k=47, odds ratio=0.773, 95% CI=0.742, 0.804), coronary artery disease (k=34, odds ratio=0.734, 95% CI=0.690, 0.781), cerebrovascular disease (k=8, odds ratio=0.810, 95% CI=0.779, 0.842), and other mixed CVDs (k=11, odds ratio=0.839, 95% CI=0.761, 0.924). Significant disparities emerged for any screening, any intervention, catheterization or revascularization in coronary artery disease, intravenous thrombolysis for stroke, and treatment with any and with specific medications for CVD across all mental disorders (except for CVD medications in mood disorders). Disparities were largest for schizophrenia, and they differed across countries. Median study quality was high (Newcastle-Ottawa Scale score, 8); higher-quality studies found larger disparities, and publication bias did not affect results.Conclusions: People with mental disorders, and those with schizophrenia in particular, receive less screening and lower-quality treatment for CVD. It is of paramount importance to address underprescribing of CVD medications and underutilization of diagnostic and therapeutic procedures across all mental disorders.Keywords: Bipolar and Related Disorders; Cardiovascular Disease; Mental Health Care/Service Delivery Systems; Physical Health; Schizophrenia Spectrum and Other Psychotic Disorders; Screening.

BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n= 9,268) and the ECLIPSE study (n= 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1%(95%CI, 2.4%-3.7%; P< .001) in COPDGene, and 2.4%(95%CI, 0.9%-4.0%; P< .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.

Objective The journal received a request to retract a paper reporting the results of a triple-blind randomized placebo-controlled trial. The present and immmediate past editors expand on the journal's decision not to retract this paper in spite of undisputable evidence of scientific misconduct on behalf of one of the investigators. Methods The editors present an ethical reflection on the request to retract this randomized clinical trial with consideration of relevant guidelines from the Committee on Publication Ethics (COPE) and the International Committee of Medical Journal Editors (ICMJE) applied to the unique contextual issues of this case. Results In this case, scientific misconduct by a blinded provider of a homeopathy intervention attempted to undermine the study blind. As part of the study, the integrity of the study blind was assessed. Neither participants nor homeopaths were able to identify whether the participant was assigned to homeopathic medicine or placebo. Central to the decision not to retract the paper was the fact that the rigorous scientific design provided evidence that the outcome of the study was not affected by the misconduct. The misconduct itself was thought to be insufficient reason to retract the paper. Conclusion Retracting a paper of which the outcome is still valid was in itself considered unethical, as it takes away the opportunity to benefit from its results, rendering the whole study useless. In such cases, scientific misconduct is better handled through other professional channels.

Objectives Limited prospective data, mostly focused on bipolar I disorder, suggests that pro-inflammatory cytokines are elevated in abnormal mood states. We evaluated whether treatment normalizes peripheral markers of inflammation in bipolar II disorder. Methods Using data from a randomized clinical trial of Interpersonal and Social Rhythm Therapy (IPSRT) + quetiapine vs. IPSRT + placebo for bipolar II depression, we examined whether these treatments for bipolar II depression impact inflammatory cytokines and whether observed changes in cytokines are associated with changes in depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD-17). Results Cytokine values were available for 33 participants who completed baseline and 20-week follow-up visits. After excluding those with CRP values > = 10 mg/L, there were 27 patients available for analysis (IPSRT + quetiapine N = 10, IPSRT + placebo N = 17). Baseline measure of inflammation did not appear to moderate treatment response, nor was change in HRSD-17 score correlated with changes in cytokines. Those who received IPSRT + quetiapine had significantly greater increases in IL-6 (p = 0.02) and TNF-α (p = 0.04), even after adjusting for changes in body mass index, than the IPSRT alone group. Descriptively, the quetiapine group showed increases in pro-inflammatory and decreases in anti-inflammatory cytokines and the psychotherapy group showed reduced pro-inflammatory cytokines. Conclusions Despite both groups showing depression improvement, this small study suggests a more pro-inflammatory cytokine profile over time with quetiapine plus psychotherapy compared to psychotherapy alone. Elevated risk of cardiovascular morbidity and mortality among those with bipolar II disorder underscores the importance of delivering treatments that do not exacerbate these risk factors.

Although much attention has appropriately been paid to suicide risk in bipolar disorder, cardiovascular disease has not received commensurate attention. People with bipolar disorder bear approximately twice the expected risk of cardiovascular disease and mortality. Several potential explanations for this alarming finding are reviewed with a focus on potential targets for clinical intervention. Many medications used to treat bipolar disorder may adversely impact risk factors for cardiovascular disease. People with bipolar disorder are additionally more likely to smoke, less likely to exercise regularly, and less likely to have healthy eating habits. Sleep problems are also nearly ubiquitous in bipolar disorder. Unacceptably, patients with bipolar disorder receive inadequate screening for and management of risk factors for cardiovascular disease, even in countries with universal access to health care. As providers with the most contact with many of these patients, psychiatrists are challenged to come to the fore in addressing this public health disparity. [ Psychiatr Ann. 2019;49(9):380–385.]

Psychological inflexibility is a multifaceted construct reflecting a rigid dominance of psychological reactions over chosen values and contingencies in guiding action. Psychological inflexibility has been related to depressive and anxiety symptoms and has been studied as a target of treatment for different forms of psychopathology. This construct, however, remains understudied among some at-risk groups. To close this gap in knowledge, the current study examined cross-sectional relations between psychological inflexibility and (1) symptoms of depression among adults with migraines (n = 2936) and (2) symptoms of anxiety and depression among adults at-risk for cardiovascular disease (n = 921). Results indicate that psychological inflexibility significantly related to depressive and anxiety symptoms among these populations. Results are discussed in terms of treatment implications for such persons.

Objective We have previously shown that the severity of anxiety symptoms during major depressive episodes is associated in a linear fashion with the proportion of weeks in depressive episodes during a subsequent 25 years of follow-up. Here, we test whether the negative prognostic implications of anxiety comorbidity extend to higher likelihoods of suicidal behavior. Methods We used the NIMH Collaborative Depression Study (CDS) cohort to test both the severity of eight anxiety symptoms and the presence or absence of four anxiety disorders as risk factors for suicide attempts or completions over a mean (SD) follow-up of 16.6 (8.5) years. Separate analyses tested potential predictors of events that occurred within 2 years and those that occurred later. Results None of the baseline anxiety manifestations were significantly associated with overall risks for past or future suicide attempts. Only the diagnosis of phobic disorder was overrepresented in the 36 who committed suicide. Psychic anxiety was a risk factor for suicide attempts beyond 2 years of follow-up, and phobic anxiety was protective of suicides within this period. Conclusions These results did not show anxiety comorbidity to be an important risk factor for suicide attempts or completions.