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The British Journal of Psychiatry : the... May 2024Circadian dysfunction is a core feature of bipolar disorder and may be due, at least in part, to abnormalities of non-visual photoreception. We critically review the...
Circadian dysfunction is a core feature of bipolar disorder and may be due, at least in part, to abnormalities of non-visual photoreception. We critically review the evidence for light hypersensitivity in bipolar disorder and discuss how this may shape future research and clinical innovation, with a focus on a possible novel mechanism of action for lithium.
Topics: Humans; Bipolar Disorder; Light
PubMed: 38174418
DOI: 10.1192/bjp.2023.150 -
Journal of Clinical PsychopharmacologyThe purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression.
METHODS
Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model.
RESULTS
Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters.
CONCLUSION
Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.
Topics: Humans; Antidepressive Agents; Bipolar Disorder; Mania; Pharmacogenetics; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 37683232
DOI: 10.1097/JCP.0000000000001747 -
Dialogues in Clinical Neuroscience Dec 2023Repetitive transcranial magnetic stimulation (TMS) is increasingly used to treat neurocognitive symptoms in mood disorders. Intermittent theta burst stimulation (iTBS)... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Repetitive transcranial magnetic stimulation (TMS) is increasingly used to treat neurocognitive symptoms in mood disorders. Intermittent theta burst stimulation (iTBS) is a brief version of TMS that may preferentially target cognitive functions. This study evaluated whether iTBS leads to cognitive improvements and associated increased hippocampal volumes in bipolar depression.
METHODS
In a two-site double-blind randomised sham controlled trial (NCT02749006), 16 patients received active iTBS to the Left Dorsolateral Prefrontal Cortex (DLPF) and 15 patients received sham stimulation across four weeks. A composite neuropsychological score and declarative memory scores served as the cognitive outcomes. Hippocampal volumes were derived from T1 weighted MRI scans using the longitudinal ComBat method to harmonise data across sites.
RESULTS
No significant improvements were observed in any cognitive variables in the active relative to the sham group; however, there was a trend for increased left hippocampal volume in the former. Left hippocampal volume increases were associated with improvements in nonverbal memory in the active group.
CONCLUSIONS
Although cognitive improvements were not associated with iTBS, the finding that hippocampal volume increases were associated with memory improvement suggests there may be some level of prefrontal-temporal neuroplasticity that could support cognitive change in future studies of iTBS in bipolar disorder.
Topics: Humans; Bipolar Disorder; Transcranial Magnetic Stimulation; Theta Rhythm; Prefrontal Cortex; Cognition; Hippocampus
PubMed: 36924413
DOI: 10.1080/19585969.2023.2186189 -
Molecular Psychiatry Jul 2023Cross-sectional neuroimaging studies show that bipolar disorder is associated with structural brain abnormalities, predominantly observed in prefrontal and temporal... (Review)
Review
Cross-sectional neuroimaging studies show that bipolar disorder is associated with structural brain abnormalities, predominantly observed in prefrontal and temporal cortex, cingulate gyrus, and subcortical regions. However, longitudinal studies are needed to elucidate whether these abnormalities presage disease onset or are consequences of disease processes, and to identify potential contributing factors. Here, we narratively review and summarize longitudinal structural magnetic resonance imaging studies that relate imaging outcomes to manic episodes. First, we conclude that longitudinal brain imaging studies suggest an association of bipolar disorder with aberrant brain changes, including both deviant decreases and increases in morphometric measures. Second, we conclude that manic episodes have been related to accelerated cortical volume and thickness decreases, with the most consistent findings occurring in prefrontal brain areas. Importantly, evidence also suggests that in contrast to healthy controls, who in general show age-related cortical decline, brain metrics remain stable or increase during euthymic periods in bipolar disorder patients, potentially reflecting structural recovering mechanisms. The findings stress the importance of preventing manic episodes. We further propose a model of prefrontal cortical trajectories in relation to the occurrence of manic episodes. Finally, we discuss potential mechanisms at play, remaining limitations, and future directions.
Topics: Humans; Bipolar Disorder; Mania; Cross-Sectional Studies; Brain; Prefrontal Cortex; Magnetic Resonance Imaging
PubMed: 37147390
DOI: 10.1038/s41380-023-02073-4 -
Medicina (Kaunas, Lithuania) Dec 2023Depressive symptoms are prominent in both major depressive disorder (MDD) and bipolar disorder (BD). However, comparative research on the network structure of...
Depressive symptoms are prominent in both major depressive disorder (MDD) and bipolar disorder (BD). However, comparative research on the network structure of depressive symptoms in these two diagnostic groups has been limited. This study aims to compare the network structure of depressive symptoms in MDD and BD, providing a deeper understanding of the depressive symptomatology of each disorder. The Zung Self-Rating Depressive Scale, a 20-item questionnaire, was administered to assess the depressive symptoms in individuals with MDD ( = 322) and BD ( = 516). A network analysis was conducted using exploratory graph analysis (EGA), and the network structure was analyzed using regularized partial correlation models. To validate the dimensionality of the Zung SDS, principal component analysis (PCA) was adopted. Centrality measures of the depressive symptoms within each group were assessed, followed by a network comparison test between the two groups. In both diagnostic groups, the network analysis revealed four distinct categories, aligning closely with the PCA results. "Depressed affect" emerged as the most central symptom in both MDD and BD. Furthermore, non-core symptoms, "Personal devaluation" in MDD and "Confusion" in BD, displayed strong centrality. The network comparison test did not reveal significant differences in the network structure between MDD and BD. The absence of significant differences in the network structures between MDD and BD suggests that the underlying mechanisms of depressive symptoms may be similar across these disorders. The identified central symptoms, including "Depressed affect", in both disorders and the distinct non-core symptoms in each highlight the complexity of the depressive symptomatology. Future research should focus on validating these symptoms as therapeutic targets and incorporate various methodologies, including non-metric dimension reduction techniques or canonical analysis.
Topics: Humans; Depressive Disorder, Major; Bipolar Disorder; Confusion; Principal Component Analysis
PubMed: 38256293
DOI: 10.3390/medicina60010032 -
Asian Journal of Psychiatry Jul 2023Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice,...
OBJECTIVE
Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar.
METHODS
Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection.
RESULTS
In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication.
CONCLUSIONS
Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.
Topics: Humans; Bipolar Disorder; Valproic Acid; Antimanic Agents; Antipsychotic Agents; Anticonvulsants; Pakistan
PubMed: 37163943
DOI: 10.1016/j.ajp.2023.103613 -
JAMA Network Open Sep 2023Predicting the onset of bipolar disorder (BD) could facilitate preventive treatments. Among risk measures, bipolar at-risk (BAR) criteria have shown promise in...
IMPORTANCE
Predicting the onset of bipolar disorder (BD) could facilitate preventive treatments. Among risk measures, bipolar at-risk (BAR) criteria have shown promise in predicting onset of bipolar disorder in the first year in clinical cohorts; however, it is not known whether BAR criteria are associated with the onset of BD in the longer term.
OBJECTIVE
To assess the association of BAR criteria with onset of BD over 10 to 13 years follow-up.
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study, completed between May 1, 2020, and November 7, 2022, included consenting people seeking help for nonpsychotic major mental health difficulties, including mood, personality, and substance use disorders, who were originally recruited at ages 15 to 25 years from a tertiary youth mental health setting in metropolitan Melbourne, Victoria, Australia, from May 1, 2008, to September 30, 2010.
EXPOSURE
Meeting BAR criteria at baseline. Criteria included subthreshold mania, cyclothymic features, subthreshold depression, and family history of BD. A matched clinical comparison group was recruited from the same help-seeking population.
MAIN OUTCOMES AND MEASURES
The primary outcome was expert consensus diagnosis of BD I or II based on the Mini International Neuropsychiatric Interview, self-reported information collected through online assessments, and linked data on mental health service utilization in Victoria over 10 to 13 years of follow-up.
RESULTS
Among 69 eligible participants, follow-up data were available for 60 (88.2%). The mean (SD) age at the end of follow-up was 32.9 (2.8) years, and 49 (81.7%) were women. A total of 28 participants met BAR criteria, and 32 were in the comparison group. In the BAR group, 8 patients (28.6%) developed BD over a mean (SD) of 11.1 (0.7) years of follow-up, and no patients in the comparison group developed BD. The risk of developing BD was higher in the BAR group than in the non-BAR group (χ21 = 70.0; P < .001). The proportions of transitions to BD were equal in the first and second halves of the follow-up period.
CONCLUSIONS AND RELEVANCE
In this cohort study of participants seeking care for mental health difficulties, patients meeting the BAR criteria were significantly more likely to transition to BD over a decade after ascertainment compared with patients not meeting the BAR criteria. The findings suggest that those meeting BAR criteria may benefit from longer-term monitoring and support. Evaluation of predictive properties in longer-term studies using a risk measure will help with implementation of BAR criteria in clinical settings.
Topics: Adolescent; Humans; Female; Male; Bipolar Disorder; Cohort Studies; Prospective Studies; Mania; Victoria
PubMed: 37713195
DOI: 10.1001/jamanetworkopen.2023.34078 -
Journal of Affective Disorders Nov 2023It remains unclear how adverse childhood experiences (ACE) and increased genetic risk for bipolar disorder (BD) interact to influence BD symptom outcomes. Here we...
BACKGROUND
It remains unclear how adverse childhood experiences (ACE) and increased genetic risk for bipolar disorder (BD) interact to influence BD symptom outcomes. Here we calculated multiple psychiatric polygenic risk scores (PRS) and used the measures of ACE to understand these gene-environment interactions.
METHOD
885 BD subjects were included for analyses. BD, ADHD, MDD and SCZ PRSs were calculated using the PRS-CS-auto method. ACEs were evaluated using the Children Life Event Questionnaire (CLEQ). Participants were divided into groups based on the presence of ACE and the total number of ACEs. The associations between total ACE number, PRSs and their interactions were evaluated using multiple linear and logistic regressions. Secondary analyses were performed to evaluate the influence of ACE and PRS on sub-phenotypes of BD.
RESULTS
The number of ACEs increased with the ADHD PRS. BD participants who had ACEs showed an earlier age of BD onset and higher odds of having rapid cycling. Increased BD PRS was associated with increased odds of developing psychotic symptoms. Higher ADHD PRS was associated with increased odds of having rapid cycling. No prediction effect was observed from MDD and SCZ PRS. And, we found no significant interaction between ACE numbers and any of the PRSs in predicting any selected BD sub-phenotypes.
LIMITATIONS
The study was limited by sample size, ACE definition, and cross-sectional data collection method.
CONCLUSIONS
The findings consolidate the importance of considering multiple psychiatric PRSs in predicting symptom outcomes among BD patients.
Topics: Child; Humans; Bipolar Disorder; Adverse Childhood Experiences; Cross-Sectional Studies; Risk Factors; Gene-Environment Interaction
PubMed: 37643680
DOI: 10.1016/j.jad.2023.08.116 -
BJPsych Open May 2024Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management... (Review)
Review
BACKGROUND
Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder.
AIMS
We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder.
METHOD
The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates.
RESULTS
We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = -3.19, 95% CI: -5.30 to -1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = -1.57, 95% CI: -2.88 to -0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP ( < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP ( < 0.05). No differences were estimated for other variables.
CONCLUSIONS
Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.
PubMed: 38708573
DOI: 10.1192/bjo.2024.51 -
JAMA Psychiatry Aug 2023Psychiatric disorders display high levels of comorbidity and genetic overlap, necessitating multivariate approaches for parsing convergent and divergent psychiatric risk...
IMPORTANCE
Psychiatric disorders display high levels of comorbidity and genetic overlap, necessitating multivariate approaches for parsing convergent and divergent psychiatric risk pathways. Identifying gene expression patterns underlying cross-disorder risk also stands to propel drug discovery and repurposing in the face of rising levels of polypharmacy.
OBJECTIVE
To identify gene expression patterns underlying genetic convergence and divergence across psychiatric disorders along with existing pharmacological interventions that target these genes.
DESIGN, SETTING, AND PARTICIPANTS
This genomic study applied a multivariate transcriptomic method, transcriptome-wide structural equation modeling (T-SEM), to investigate gene expression patterns associated with 5 genomic factors indexing shared risk across 13 major psychiatric disorders. Follow-up tests, including overlap with gene sets for other outcomes and phenome-wide association studies, were conducted to better characterize T-SEM results. The Broad Institute Connectivity Map Drug Repurposing Database and Drug-Gene Interaction Database public databases of drug-gene pairs were used to identify drugs that could be repurposed to target genes found to be associated with cross-disorder risk. Data were collected from database inception up to February 20, 2023.
MAIN OUTCOMES AND MEASURES
Gene expression patterns associated with genomic factors or disorder-specific risk and existing drugs that target these genes.
RESULTS
In total, T-SEM identified 466 genes whose expression was significantly associated (z ≥ 5.02) with genomic factors and 36 genes with disorder-specific effects. Most associated genes were found for a thought disorders factor, defined by bipolar disorder and schizophrenia. Several existing pharmacological interventions were identified that could be repurposed to target genes whose expression was associated with the thought disorders factor or a transdiagnostic p factor defined by all 13 disorders.
CONCLUSIONS AND RELEVANCE
The findings from this study shed light on patterns of gene expression associated with genetic overlap and uniqueness across psychiatric disorders. Future versions of the multivariate drug repurposing framework outlined here have the potential to identify novel pharmacological interventions for increasingly common, comorbid psychiatric presentations.
Topics: Humans; Transcriptome; Drug Repositioning; Latent Class Analysis; Mental Disorders; Bipolar Disorder; Genome-Wide Association Study; Genetic Predisposition to Disease
PubMed: 37314780
DOI: 10.1001/jamapsychiatry.2023.1808