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Psychotic symptoms, that we defined as delusions or hallucinations, are common in bipolar disorders (BD). This systematic review and meta-analysis aims to synthesise the literature on both lifetime and point prevalence rates of psychotic symptoms across different BD subtypes, including both BD type I (BDI) and BD type II (BDII). We performed a systematic search of Medline, PsycINFO, Embase and Cochrane Library until 5 August 2021. Fifty-four studies (N = 23 461) of adults with BD met the predefined inclusion criteria for evaluating lifetime prevalence, and 24 studies (N = 6480) for evaluating point prevalence. Quality assessment and assessment of publication bias were performed. Prevalence rates were calculated using random effects meta-analysis, here expressed as percentages with a 95% confidence interval (CI). In studies of at least moderate quality, the pooled lifetime prevalence of psychotic symptoms in BDI was 63% (95% CI 57.5–68) and 22% (95% CI 14–33) in BDII. For BDI inpatients, the pooled lifetime prevalence was 71% (95% CI 61–79). There were no studies of community samples or inpatient BDII. The pooled point prevalence of psychotic symptoms in BDI was 54% (95 CI 41–67). The point prevalence was 57% (95% CI 47–66) in manic episodes and 13% (95% CI 7–23.5) in depressive episodes. There were not enough studies in BDII, BDI depression, mixed episodes and outpatient BDI. The pooled prevalence of psychotic symptoms in BDI may be higher than previously reported. More studies are needed for depressive and mixed episodes and community samples. Prospero registration number: CRD 42017052706.

The neuroanatomical alteration in bipolar II depression (BDII-D) and its associations with inflammation, childhood adversity, and psychiatric symptoms are currently unclear. We hypothesize that neuroanatomical deficits will be related to higher inflammation, greater childhood adversity, and worse psychiatric symptoms in BDII-D. Voxel- and surface-based morphometry was performed using the CAT toolbox in 150 BDII-D patients and 155 healthy controls (HCs). Partial Pearson correlations followed by multiple comparison correction was used to indicate significant relationships between neuroanatomy and inflammation, childhood adversity, and psychiatric symptoms. Compared with HCs, the BDII-D group demonstrated significantly smaller gray matter volumes (GMVs) in frontostriatal and fronto-cerebellar area, insula, rectus, and temporal gyrus, while significantly thinner cortices were found in frontal and temporal areas. In BDII-D, smaller GMV in the right middle frontal gyrus (MFG) was correlated with greater sexual abuse ( = -0.348, < 0.001) while larger GMV in the right orbital MFG was correlated with greater physical neglect ( = 0.254, = 0.03). Higher WBC count ( = -0.227, = 0.015) and IL-6 levels ( = -0.266, = 0.015) was associated with smaller GMVs in fronto-cerebellar area in BDII-D. Greater positive symptoms was correlated with larger GMVs of the left middle temporal pole ( = 0.245, = 0.03). Neuroanatomical alterations in frontostriatal and fronto-cerebellar area, insula, rectus, temporal gyrus volumes, and frontal-temporal thickness may reflect a core pathophysiological mechanism of BDII-D, which are related to inflammation, trauma, and psychiatric symptoms in BDII-D.

Atypical depressive disorder and bipolar disorder often present with symptoms like emotional instability and impulsive behaviors. Various treatments, both pharmaceutical and non-pharmacological, are employed to manage these conditions. Transcranial direct current stimulation (tDCS) is a modern treatment option that has shown promise with minimal side effects. This study aims to compare the effectiveness of tDCS on emotional instability and impulsivity in individuals with atypical depression and bipolar type II. This study utilized a semi-experimental, pre-test-post-test design with a control group. The participants were patients diagnosed with atypical and bipolar depression, all of whom were referred from the neuropsychiatric clinic at Sina Hospital in Hamedan, Iran. Two hundred instability and impulsivity questionnaires were distributed among the patients using a purposeful sampling method. From these, participants were randomly assigned into four groups of 20 individuals each. The research tools included transcranial direct current stimulation (tDCS), delivered in ten consecutive sessions (30 min each, 2 mA) with the anode at F3 and the cathode at F4; the sham condition used the same montage with current discontinued after 30 s to ensure blinding., the Eysenck Personality Questionnaire (EPQ) by Eysenck and Sybil, and Barratt Impulsiveness Scale (BIS). Data analysis using covariance and multivariate covariance analysis (MANCOVA) revealed a significant difference in emotional instability and impulsivity scores between the experimental and control groups for individuals with atypical depression and bipolar type II. Direct current electrical brain stimulation was found to reduce emotional instability in these groups, leading to improved emotional stability and reduced impulsivity in people with atypical depression and bipolar disorder. The results of this study confirm the potential of direct current electrical brain stimulation in reducing emotional instability and impulsivity in individuals with atypical depression. The emergence of tDCS as a promising non-pharmacological treatment option for managing these symptoms in people with both atypical depression and bipolar disorder type II is reassuring. This method modulates the prefrontal cortex’s activity, a brain region crucial for planning, decision-making, and emotional regulation. The significant potential of tDCS as a non-pharmacological intervention for atypical depression and bipolar disorder type II is a positive sign for the future. However, further research is necessary to fully realize its benefits.

Introduction Bipolar disorder is a psychiatric condition characterized by the coexistence of depression and mania. Diagnosis of this disorder can be challenging due to limited pathologic and experimental tools. Treatment compliance is often poor due to medication side effects. Although cathepsin is known to play a significant role in diseases such as tumors and osteoporosis, its role in psychiatric disorders is not yet fully understood. Objective The aim of this study was to investigate the relationship between cathepsin in the blood circulation and bipolar disorder. Methods The causal relationship between cathepsin and different subtypes of bipolar affective disorder was explored using bidirectional Mendelian randomization analysis and multivariate analysis. Results It was found that cathepsin H level was a protective factor for type II bipolar disorder. No potential causal relationship was found between cathepsin H and type I bipolar disorder, but cathepsin B changes with the development of type I bipolar disorder. A causal relationship was found between cathepsin H and cerebral dopamine neurotrophic factor. Conclusions In conclusion, cathepsin H may be a diagnostic target for bipolar II disorder and may play a guiding role in clinical diagnosis. Cathepsin H may have an effect on BD through cerebral dopamine neurotrophic factor.

Current approaches to identifying individuals at risk for psychosis capture only a small proportion of future psychotic disorders. Recent Finnish research suggests a substantial proportion of individuals at risk of psychosis attend child and adolescent mental health services (CAMHS) earlier in life, creating important opportunities for prediction and prevention. To what extent this is true outside Finland is unknown. To establish the proportion of psychotic and bipolar disorder diagnoses that occurred in individuals who had attended CAMHS in Wales, UK, and whether, within CAMHS, certain factors were associated with increased psychosis risk. We examined healthcare contacts for individuals born between 1991 and 1998 ( = 348 226), followed to age 25-32. Using linked administrative healthcare records, we identified all psychotic and bipolar disorder diagnoses in the population, then determined the proportion of cases where the individual had attended CAMHS. Regression analyses examined associations between sociodemographic and clinical risk markers with psychotic and bipolar disorder outcomes. Among individuals diagnosed with a psychotic or bipolar disorder, 44.78% had attended CAMHS (hazard ratio = 6.28, 95% CI = 5.92-6.65). Low birth weight (odds ratio = 1.33, 95% CI = 1.15-1.53), out-of-home care experience (odds ratio = 2.05, 95% CI = 1.77-2.38), in-patient CAMHS admission (odds ratio = 1.49, 95% CI = 1.29-1.72) and attending CAMHS in childhood (in addition to adolescence; odds ratio = 1.16, 95% CI = 1.02-1.30) were all within-CAMHS risk markers for psychotic and bipolar disorders. A substantial proportion (45%) of future psychotic and bipolar disorder cases emerge in individuals who had attended CAMHS, demonstrating large-scale opportunities for early intervention and prevention within CAMHS.

Mood disorders are among the leading causes of disease burden worldwide, with 20-70% of affected individuals experiencing comorbid premenstrual disorders. This systematic review and meta-analysis investigated the comorbidity of premenstrual dysphoric disorder (PMDD) or premenstrual syndrome (PMS) with non-reproductive mood disorders. We aimed to determine the pooled prevalence of PMDD/PMS with adult mood disorders, assess the impact of comorbidity on clinical course and summarise the associated neurobiological findings. Eligible studies were identified through Embase, MEDLINE and APA PsycINFO from inception to 22 January 2024 (PROSPERO, no. CRD42021246796). Studies on women ('females') with diagnoses of PMDD/PMS and mood disorders were included. Risk of bias was assessed using National Institutes of Health quality assessment tools. A random-effects, pooled-prevalence meta-analysis was conducted using the Comprehensive Meta-Analysis software, categorising diagnostic sampling strategies as follows: mood disorders diagnosed first, PMDD/PMS diagnosed first or concurrent diagnoses. A narrative synthesis explored secondary outcomes, including illness course and biomarkers. A total of 39 studies were included, with 36 of these ( = 3646) contributing to the meta-analysis. Seven studies focused on bipolar disorders, 18 on unipolar depressive disorders and 14 on mixed samples of bipolar and unipolar disorders. Random-effects pooled-prevalence meta-analyses showed consistently high comorbidity rates between PMDD/PMS and mood disorders, ranging from 42% (95% CI: 30%, 55%) to 49% (95% CI: 38%, 60%) across sampling strategies. Risk of bias varied, with methodological heterogeneity noted. This review underscores high comorbidity rates between PMDD/PMS and mood disorders, regardless of sampling strategy, and highlights the need for research into clinical and neurobiological characteristics specific to this comorbidity. Limitations include study heterogeneity, reliance on cross-sectional designs and provisional PMDD/PMS diagnoses. Future research should address these gaps to inform diagnostic and therapeutic advancements tailored to this population.

Aim: Genome-wide association studies (GWAS) analyses have revealed genetic evidence of bipolar disorder (BD), but little is known about the genetic structure of BD subtypes. We aimed to investigate the genetic overlap and distinction of bipolar type I (BD I) & type II (BD II) by conducting integrative post-GWAS analyses. Methods: We utilized single nucleotide polymorphism (SNP)–level approaches to uncover correlated and distinct genetic loci. Transcriptome-wide association analyses (TWAS) were then approached to pinpoint functional genes expressed in specific brain tissues and blood. Next, we performed cross-phenotype analysis, including exploring the potential causal associations between two BD subtypes and lithium responses and comparing the difference in genetic structures among four different psychiatric traits. Results: SNP-level evidence revealed three genomic loci, SLC25A17, ZNF184 , and RPL10AP3 , shared by BD I and II, and one locus ( MAD1L1 ) and significant gene sets involved in calcium channel activity, neural and synapsed signals that distinguished two subtypes. TWAS data implicated different genes affecting BD I and II through expression in specific brain regions (nucleus accumbens for BD I). Cross-phenotype analyses indicated that BD I and II share continuous genetic structures with schizophrenia and major depressive disorder, which help fill the gaps left by the dichotomy of mental disorders. Conclusion: These combined evidences illustrate genetic convergence and divergence between BD I and II and provide an underlying biological and trans-diagnostic insight into major psychiatric disorders.

Introduction Bipolar disorders (BDs) comprise different variants of chronic, comorbid, and disabling conditions, with relevant suicide and suicide attempt rates. The hypothesis that BD types I (BDI) and II (BDII) represent more and less severe forms of illness, respectively, has been increasingly questioned over recent years, justifying additional investigation to better characterize related sociodemographic and clinical profiles. A sample of 217 outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)-described BD (141 BDI, 76 BDII), without a current syndromal mood episode, was recruited, and sociodemographic and clinical characteristics of BDI and II patients were compared. BDII patients had significantly more favorable sociodemographics, in relation to occupational stability, cohabitation, and marital status. However, BDII compared with BDI patients had significantly longer duration of untreated illness, more frequent lifetime anxiety disorders comorbidity, longer most recent episode duration, higher rate of depressive first/most recent episode, and more current antidepressant use. In contrast, BDI compared with BDII patients had significantly more severe illness in terms of earlier age at onset; higher rate of elevated first/most recent episode, lifetime hospitalizations, and involuntary commitments; lower Global Assessment of Functioning score; and more current antipsychotic use. BDI and II patients had similar duration of illness, psychiatric family history, lifetime number of suicide attempts, current subthreshold symptoms, history of stressful life events, and overall psychiatric/medical comorbidity. BDII compared with BDI patients had more favorable sociodemographic features, but a mixture of specific unfavorable illness characteristics, confirming that BDII is not just a milder form of BD and requires further investigation in the field.

BackgroundThe distinction between bipolar I and bipolar II disorder and its treatment implications have been a matter of ongoing debate. The aim of this study was to examine differences between patients with bipolar I and II disorders with particular emphasis on the early phases of the disorders.Methods808 subjects diagnosed with bipolar I (N = 587) or bipolar II disorder (N = 221) according to DSM-IV criteria were recruited between April 1994 and March 2022 from tertiary-level mood disorder clinics. Sociodemographic and clinical variables concerning psychiatric and medical comorbidities, family history, illness course, suicidal behavior, and response to treatment were compared between the bipolar disorder types.ResultsBipolar II disorder patients were more frequently women, older, married or widowed. Bipolar II disorder was associated with later “bipolar” presentation, higher age at first (hypo)mania and treatment, less frequent referral after a single episode, and more episodes before lithium treatment. A higher proportion of first-degree relatives of bipolar II patients were affected by major depression and anxiety disorders. The course of bipolar II disorder was typically characterized by depressive onset, early depressive episodes, multiple depressive recurrences, and depressive predominant polarity; less often by (hypo)mania or (hypo)mania-depression cycles at onset or during the early course. The lifetime clinical course was more frequently rated as chronic fluctuating than episodic. More patients with bipolar II disorder had a history of rapid cycling and/or high number of episodes. Mood stabilizers and antipsychotics were prescribed less frequently during the early course of bipolar II disorder, while antidepressants were more common. We found no differences in global functioning, lifetime suicide attempts, family history of suicide, age at onset of mood disorders and depressive episodes, and lithium response.ConclusionsDifferences between bipolar I and II disorders are not limited to the severity of (hypo)manic syndromes but include patterns of clinical course and family history. Caution in the use of potentially mood-destabilizing agents is warranted during the early course of bipolar II disorder.

Background Bipolar disorder is a serious mental illness, which requires new strategies for prevention and management. Recent evidence suggests that a ketogenic diet may be an effective intervention. This research aimed to explore the feasibility and acceptability of a ketogenic diet intervention for bipolar disorder, fidelity to its behavioural components and the experiences of the participants and research clinicians involved. Methods A mixed-methods process evaluation was conducted. Semi-structured telephone interviews were carried out with 15 participants 1–2 months after completing a 6–8 week modified ketogenic diet intervention, and 4 research clinicians from the study team following the completion of data collection. Data were thematically analysed. Fidelity checklists completed by research dietitians were analysed using descriptive count and percentage statistics. Findings are reported post-hoc, following the analysis and publication of the main pilot study findings. Reporting was guided by the COREQ checklist. Results Five themes were identified in the qualitative data: (1) ‘ Encouraging entry and supporting exit’ (e.g. recognising and managing participants’ varied motives and expectations, including around weight loss and symptom alleviation); (2) ‘ Challenging but potentially transformational ,’ which reflects that while it can be difficult to initiate and maintain a ketogenic diet day-to-day, many participants perceived physical and psychological benefits (e.g. significant weight loss, mood stability and enhanced ability to focus); (3) ‘Intervention facilitators ,’ including a range of behavioural (e.g. goal setting), social (e.g. family and dietitians) and technological (e.g. apps for monitoring) support mechanisms; (4) ‘Intervention barriers’ (e.g. dietary preferences, concerns about the diet and its impact, the testing burden and capacity of the delivery team); and (5) ‘The wider context’ (e.g. the cost of living and sociocultural expectations) was a crucial factor explaining differential experiences. Overall, descriptive analyses indicated moderate-to-good fidelity to the behaviour change components of the study. Conclusion We provide novel insight into the experiences of people living with bipolar disorder initiating and following a ketogenic diet, as well as those of research clinicians who support the intervention. Future trials may benefit from increased clinical research capacity, better-defined entry and exit routes, additional interpersonal support, and greater understanding of how social and societal factors impact participation. Trial registration Study registration number: ISRCTN61613198 (02/03/22).