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JAMA Oct 2023Bipolar disorder affects approximately 8 million adults in the US and approximately 40 million individuals worldwide. (Review)
Review
IMPORTANCE
Bipolar disorder affects approximately 8 million adults in the US and approximately 40 million individuals worldwide.
OBSERVATIONS
Bipolar disorder is characterized by recurrent episodes of depression and mania or hypomania. Bipolar depressive episodes are similar to major depressive episodes. Manic and hypomanic episodes are characterized by a distinct change in mood and behavior during discrete time periods. The age of onset is usually between 15 and 25 years, and depression is the most frequent initial presentation. Approximately 75% of symptomatic time consists of depressive episodes or symptoms. Early diagnosis and treatment are associated with a more favorable prognosis. Diagnosis and optimal treatment are often delayed by a mean of approximately 9 years following an initial depressive episode. Long-term treatment consists of mood stabilizers, such as lithium, valproate, and lamotrigine. Antipsychotic agents, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine, are recommended, but some are associated with weight gain. Antidepressants are not recommended as monotherapy. More than 50% of patients with bipolar disorder are not adherent to treatment. Life expectancy is reduced by approximately 12 to 14 years in people with bipolar disorder, with a 1.6-fold to 2-fold increase in cardiovascular mortality occurring a mean of 17 years earlier compared with the general population. Prevalence rates of metabolic syndrome (37%), obesity (21%), cigarette smoking (45%), and type 2 diabetes (14%) are higher among people with bipolar disorder, contributing to the risk of early mortality. The annual suicide rate is approximately 0.9% among individuals with bipolar disorder, compared with 0.014% in the general population. Approximately 15% to 20% of people with bipolar disorder die by suicide.
CONCLUSIONS AND RELEVANCE
Bipolar disorder affects approximately 8 million adults in the US. First-line therapy includes mood stabilizers, such as lithium, anticonvulsants, such as valproate and lamotrigine, and atypical antipsychotic drugs, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine.
Topics: Humans; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Psychotropic Drugs
PubMed: 37815563
DOI: 10.1001/jama.2023.18588 -
JAMA Psychiatry Aug 2023Cannabis use is increasing worldwide and is suspected to be associated with increased risk of psychiatric disorders; however, the association with affective disorders...
IMPORTANCE
Cannabis use is increasing worldwide and is suspected to be associated with increased risk of psychiatric disorders; however, the association with affective disorders has been insufficiently studied.
OBJECTIVE
To examine whether cannabis use disorder (CUD) is associated with an increased risk of psychotic and nonpsychotic unipolar depression and bipolar disorder and to compare associations of CUD with psychotic and nonpsychotic subtypes of these diagnoses.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, population-based cohort study using Danish nationwide registers included all individuals born in Denmark before December 31, 2005, who were alive, aged at least 16 years, and living in Denmark between January 1, 1995, and December 31, 2021.
EXPOSURE
Register-based diagnosis of CUD.
MAIN OUTCOME AND MEASURES
The main outcome was register-based diagnosis of psychotic or nonpsychotic unipolar depression or bipolar disorder. Associations between CUD and subsequent affective disorders were estimated as hazard ratios (HRs) using Cox proportional hazards regression with time-varying information on CUD, adjusting for sex; alcohol use disorder; substance use disorder; having been born in Denmark; calendar year; parental educational level (highest attained); parental cannabis, alcohol, or substance use disorders; and parental affective disorders.
RESULTS
A total of 6 651 765 individuals (50.3% female) were followed up for 119 526 786 person-years. Cannabis use disorder was associated with an increased risk of unipolar depression (HR, 1.84; 95% CI, 1.78-1.90), psychotic unipolar depression (HR, 1.97; 95% CI, 1.73-2.25), and nonpsychotic unipolar depression (HR, 1.83; 95% CI, 1.77-1.89). Cannabis use was associated with an increased risk of bipolar disorder in men (HR, 2.96; 95% CI, 2.73-3.21) and women (HR, 2.54; 95% CI, 2.31-2.80), psychotic bipolar disorder (HR, 4.05; 95% CI, 3.52-4.65), and nonpsychotic bipolar disorder in men (HR, 2.96; 95% CI, 2.73-3.21) and women (HR, 2.60; 95% CI, 2.36-2.85). Cannabis use disorder was associated with higher risk for psychotic than nonpsychotic subtypes of bipolar disorder (relative HR, 1.48; 95% CI, 1.21-1.81) but not unipolar depression (relative HR, 1.08; 95% CI, 0.92-1.27).
CONCLUSIONS AND RELEVANCE
This population-based cohort study found that CUD was associated with an increased risk of psychotic and nonpsychotic bipolar disorder and unipolar depression. These findings may inform policies regarding the legal status and control of cannabis use.
Topics: Male; Female; Humans; Bipolar Disorder; Depression; Cohort Studies; Prospective Studies; Marijuana Abuse; Substance-Related Disorders; Depressive Disorder, Major
PubMed: 37223912
DOI: 10.1001/jamapsychiatry.2023.1256 -
Journal of Psychopharmacology (Oxford,... Oct 2023Postpartum psychosis (PPP) is a psychiatric emergency that generally warrants acute inpatient care. PPP is marked by the sudden onset of affective and psychotic symptoms... (Review)
Review
BACKGROUND
Postpartum psychosis (PPP) is a psychiatric emergency that generally warrants acute inpatient care. PPP is marked by the sudden onset of affective and psychotic symptoms with a rapid deterioration in mental state. Evidence suggests that PPP is a discrete disorder on the bipolar disorder spectrum with a distinct treatment profile and prognosis.
METHODS
We conducted a PubMed database search for various terms involving PPP and its treatment and included peer-reviewed articles published in English.
OBJECTIVE
To provide a treatment algorithm for the management of PPP based on available evidence.
RESULTS
Pharmacological therapy is the mainstay of PPP management in the acute phase. Evidence points to a combination of antipsychotics and lithium in the acute treatment of PPP. Electroconvulsive therapy can offer a rapid treatment response where required. Lithium appears to have the best evidence for relapse prevention and prophylaxis in PPP. Psychoeducation is essential and psychosocial interventions used in bipolar disorder may be effective in PPP.
CONCLUSION
Early detection and prompt treatment with antipsychotics and lithium, followed by maintenance treatment with lithium, is associated with a favourable prognosis in PPP.
Topics: Female; Humans; Lithium; Psychotic Disorders; Bipolar Disorder; Antipsychotic Agents; Postpartum Period; Algorithms
PubMed: 37515460
DOI: 10.1177/02698811231181573 -
JAMA Psychiatry Jan 2024Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools.
IMPORTANCE
Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools.
OBJECTIVE
To identify a reproducible metabolomic biomarker signature in patient dried blood spots (DBSs) that differentiates BD from MDD during depressive episodes and assess its added value when combined with self-reported patient information.
DESIGN, SETTING, AND PARTICIPANTS
This diagnostic analysis used samples and data from the Delta study, conducted in the UK between April 27, 2018, and February 6, 2020. The primary objective was to identify BD in patients with a recent (within the past 5 years) diagnosis of MDD and current depressive symptoms (Patient Health Questionnaire-9 score of 5 or more). Participants were recruited online through voluntary response sampling. The analysis was carried out between February 2022 and July 2023.
MAIN OUTCOMES AND MEASURES
Patient data were collected using a purpose-built online questionnaire (n = 635 questions). DBS metabolites (n = 630) were analyzed using a targeted mass spectrometry-based platform. Mood disorder diagnoses were established using the Composite International Diagnostic Interview.
RESULTS
Of 241 patients in the discovery cohort, 170 (70.5%) were female; 67 (27.8%) were subsequently diagnosed with BD and 174 (72.2%) were confirmed as having MDD; and the mean (SD) age was 28.1 (7.1) years. Of 30 participants in the validation cohort, 16 (53%) were female; 9 (30%) were diagnosed with BD and 21 (70%) with MDD; and the mean (SD) age was 25.4 (6.3) years. DBS metabolite levels were assessed in 241 patients with depressive symptoms with a recent diagnosis of MDD, of whom 67 were subsequently diagnosed with BD by the Composite International Diagnostic Interview and 174 were confirmed as having MDD. The identified 17-biomarker panel provided a mean (SD) cross-validated area under the receiver operating characteristic curve (AUROC) of 0.71 (SD, 0.12; P < .001), with ceramide d18:0/24:1 emerging as the strongest biomarker. Combining biomarker data with patient-reported information significantly enhanced diagnostic performance of models based on extensive demographic data, PHQ-9 scores, and the outcomes from the Mood Disorder Questionnaire. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of MDD (n = 21) or BD (n = 9) during the study's 1-year follow-up period, with a mean (SD) AUROC of 0.73 (0.06; P < .001).
CONCLUSIONS AND RELEVANCE
This study provides a proof of concept for developing an accessible biomarker test to facilitate the differential diagnosis of BD and MDD and highlights the potential involvement of ceramides in the pathophysiological mechanisms of mood disorders.
Topics: Humans; Female; Adult; Male; Bipolar Disorder; Depressive Disorder, Major; Mood Disorders; Diagnosis, Differential; Biomarkers
PubMed: 37878349
DOI: 10.1001/jamapsychiatry.2023.4096 -
Bipolar Disorders Sep 2023This article examines the ongoing debate concerning the diagnosis of bipolar disorder in children and adolescents. This contentious issue has generated robust discussion... (Review)
Review
AIMS
This article examines the ongoing debate concerning the diagnosis of bipolar disorder in children and adolescents. This contentious issue has generated robust discussion over the past two decades without consensus, and as such the true prevalence of so-called paediatric bipolar disorder (PBD) remains unknown. In this article we offer a solution to break this deadlock.
METHODS
Recent meta-analyses and additional literature concerning the definition and prevalence of PBD was critically reviewed with a view to understanding the perspectives of those developing the taxonomy of PBD, and those engaged in research and clinical practice.
RESULTS
A key finding is the lack of iteration and meaningful communication between the various groups interested in PBD that stems from deep-seated problems within our classificatory systems. This undermines our research efforts and complicates clinical practice. These problems make the already difficult diagnosis of bipolar disorder in adults even more challenging to transpose to younger populations, and additional complexities arise when parsing clinical phenomenology from normative developmental changes in youth. Therefore, in those manifesting bipolar symptoms post-puberty, we argue for the use of adolescent bipolar disorder to describe bipolar symptoms whereas in pre-pubertal children, we propose a reconceptualisation that allows symptomatic treatment to be advanced whilst requiring critical review of these symptoms over time.
CONCLUSION
Significant changes in our current taxonomy are necessary and to be clinically meaningful, these revisions to our diagnoses need to be developmentally-informed.
Topics: Humans; Adolescent; Child; Bipolar Disorder; Consensus; Prevalence
PubMed: 37433682
DOI: 10.1111/bdi.13367 -
Current Opinion in Neurobiology Dec 2023This review focuses on recent advances made towards understanding the neurobiology of bipolar disorder (BD), a chronic neuropsychiatric illness characterized by altered... (Review)
Review
This review focuses on recent advances made towards understanding the neurobiology of bipolar disorder (BD), a chronic neuropsychiatric illness characterized by altered mood and energy states. The past few years have seen the completion of the largest genetic studies by far, which have emphasized the polygenic nature of BD as well as it's connection to other psychiatric illnesses. Furthermore, the use of inducible pluripotent stem cells has rapidly expanded. These studies support previous work that implicates dysregulation of neurodevelopment, mitochondria, and calcium homeostasis, while also allowing for investigation into the underlying mechanisms of individual responsivity to lithium. Sleep and circadian rhythms have also been heavily implicated in BD, from disruptions in activity patterns to molecular abnormalities.
Topics: Humans; Bipolar Disorder; Lithium; Circadian Rhythm; Sleep
PubMed: 38223491
DOI: 10.1016/j.conb.2023.102801 -
Neuroscience and Biobehavioral Reviews Sep 2023This review and meta-analysis aimed to describe the existing literature on interventions for bipolar disorder (BD) targeting the 6 pillars of Lifestyle Psychiatry: diet,... (Meta-Analysis)
Meta-Analysis Review
This review and meta-analysis aimed to describe the existing literature on interventions for bipolar disorder (BD) targeting the 6 pillars of Lifestyle Psychiatry: diet, physical activity (PA), substance use (SU), sleep, stress management, and social relationships (SR). Randomized Controlled Trials that examined the efficacy of lifestyle interventions targeting improvement in depressive/(hypo)manic symptom severity, lifestyle patterns, functioning, quality of life, and/or circadian rhythms were included. The systematic review included 18 studies, while the meta-analysis included studies targeting the same lifestyle domains and outcomes. Sleep (n = 10), PA (n = 9), and diet (n = 8) were the most targeted domains, while SU, SM and SR were least targeted (n = 4 each). Combined diet and PA interventions led to significant improvements in depressive symptoms (SMD: -0.46; 95%CI: -0.88, -0.04; p = 0.03), and functioning (SMD: -0.47; 95%CI: -0.89, -0.05; p = 0.03). Sleep interventions also led to significant improvements in depressive symptoms (SMD: -0.80; 95%CI: -1.21, -0.39; p < 0.01). Future research should focus on developing more multidimensional lifestyle interventions for a potentially greater impact on clinical and functional outcomes of BD.
Topics: Humans; Bipolar Disorder; Quality of Life; Life Style; Exercise; Psychotherapy
PubMed: 37263531
DOI: 10.1016/j.neubiorev.2023.105257 -
The Lancet. Psychiatry Sep 2023Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines required updated evidence synthesis to improve their current recommendations. In order to inform evidence-based prescribing, we investigated the comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression.
METHODS
We conducted a systematic review and network meta-analysis. We searched for randomised controlled trials comparing pharmacological interventions with each other or placebo in adults with acute bipolar depression (type I, type II, or not otherwise specified), excluding those with substance misuse, unipolar depression, or schizophrenia, in MEDLINE, Embase, PsycINFO, Google Scholar, Cochrane Library, Web of Knowledge, CINAHL, and LILACS from database inception up to April 13, 2023. Criteria for eligibility were a duration of 2-16 weeks with masked outcome assessments, and we included combination, add-on design, and monotherapy studies. The co-primary outcomes were depressive symptoms, examined with standardised mean differences (SMDs), and manic switch, examined with odds ratios (ORs). We also investigated dropouts due to any reason, inefficacy, adverse events, and important side-effects as secondary outcomes. The confidence in the evidence was evaluated using Confidence-In-Network-Meta-Analysis (CINeMA). The study was registered with PROSPERO, CRD42020171726.
RESULTS
We analysed data from 101 randomised controlled trials covering 20 081 participants, 8063 men (41·7%) and 11 263 women (58·3%; sex not available in four studies), mean age 41·0 years (range of means 28·7-53·6 years), and 68 medications and placebo. Ethnicity data were not available. With moderate confidence in the evidence, olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were more efficacious than placebo in reducing depressive symptoms, with SMDs ranging from 0·41 (95% CI 0·19-0·64) for olanzapine plus fluoxetine to 0·16 (0·03-0·29) for lamotrigine. Several other drugs might also be efficacious, but the confidence in the evidence was very low to low. Antidepressants as a class seem to be efficacious, but had a higher risk for manic switch compared to antipsychotics. Medications differed in their side-effect profiles.
INTERPRETATION
This is, to our knowledge, the largest network meta-analysis of pharmacotherapy for bipolar depression to date. Olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were found to be more efficacious than placebo in adults with acute bipolar depression, with good confidence in the evidence, and to differ in their side-effect profiles. These findings can inform evidence-based care and the development of treatment guidelines internationally.
FUNDING
None.
Topics: Male; Adult; Female; Humans; Middle Aged; Bipolar Disorder; Depression; Fluoxetine; Lamotrigine; Olanzapine; Lurasidone Hydrochloride; Quetiapine Fumarate; Network Meta-Analysis; Drug-Related Side Effects and Adverse Reactions
PubMed: 37595997
DOI: 10.1016/S2215-0366(23)00199-2 -
Schizophrenia Bulletin Sep 2023Psychiatric disorders impose a huge health and economic burden on modern society. However, there is currently no proven completely effective treatment available, partly...
BACKGROUND AND HYPOTHESIS
Psychiatric disorders impose a huge health and economic burden on modern society. However, there is currently no proven completely effective treatment available, partly owing to the inefficiency of drug target identification and validation. We aim to identify therapeutic targets relevant to psychiatric disorders by conducting Mendelian randomization (MR) analysis.
STUDY DESIGN
We performed genome-wide MR analysis by integrating expression quantitative trait loci (eQTL) of 4479 actionable genes that encode druggable proteins and genetic summary statistics from genome-wide association studies of psychiatric disorders. After conducting colocalization analysis on the brain MR findings, we employed protein quantitative trait loci (pQTL) data as genetic proposed instruments for intersecting the colocalized genes to provide further genetic evidence.
STUDY RESULTS
By performing MR and colocalization analysis with eQTL genetic instruments, we obtained 31 promising drug targets for psychiatric disorders, including 21 significant genes for schizophrenia, 7 for bipolar disorder, 2 for depression, 1 for attention deficit and hyperactivity (ADHD) and none for autism spectrum disorder. Combining MR results using pQTL genetic instruments, we finally proposed 8 drug-targeting genes supported by the strongest MR evidence, including gene ACE, BTN3A3, HAPLN4, MAPK3 and NEK4 for schizophrenia, gene NEK4 and HAPLN4 for bipolar disorder, and gene TIE1 for ADHD.
CONCLUSIONS
Our findings with genetic support were more likely to be to succeed in clinical trials. In addition, our study prioritizes approved drug targets for the development of new therapies and provides critical drug reuse opportunities for psychiatric disorders.
Topics: Humans; Autism Spectrum Disorder; Genome-Wide Association Study; Mendelian Randomization Analysis; Bipolar Disorder; Attention Deficit Disorder with Hyperactivity; Polymorphism, Single Nucleotide
PubMed: 37418754
DOI: 10.1093/schbul/sbad100 -
Ugeskrift For Laeger Apr 2024ADHD and bipolar disorder (BP) commonly coexist, and both share key symptoms, depending on affective state and emotional dysregulation. The overlap poses diagnostic... (Review)
Review
ADHD and bipolar disorder (BP) commonly coexist, and both share key symptoms, depending on affective state and emotional dysregulation. The overlap poses diagnostic challenges and may lead to underdiagnoses. Comorbid cases exhibit worsened symptom burden, increased psychiatric morbidity, admissions, and suicide attempts. Treating BP before ADHD is recommended. Stimulant use combined with mood stabilisers may be effective and relatively safe; however, this review finds that well-designed randomised controlled studies in the area is warranted.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Adult; Central Nervous System Stimulants
PubMed: 38708700
DOI: 10.61409/V10230620