International Journal of Bipolar Disorders最新文献

Background: Both bipolar disorder (BD) and epilepsy (ES) have been linked to polycystic ovary syndrome (PCOS) that is one of the most common endocrine disorders in women of reproductive age. The antiseizures medication valproate is widely used in the treatment of both disorders but has been suspected to increase the risk of PCOS. Previous studies have been limited by small sample sizes and heterogeneous definitions. We aimed to investigate the association between valproate exposure and incident PCOS in females with BS and ES.

Methods: We conducted a register-based cohort study including all females in Denmark with a first diagnosis of BD (ICD-10: F30.x-F31.x) or ES (ICD-10: G40.x) between January 1, 2000, and July 31, 2022. Women with BD, ES, valproate exposure, or PCOS prior to January 1, 2000, were excluded. Exposure to valproate was primarily modeled as current cumulative exposure. We also included a never/ever analysis and an overall cumulative analysis, accumulating dosages over the entire study period. The outcome was incident PCOS (ICD-10: E28.2). Cox regression models adjusted for age at diagnosis and calendar year were applied.

Results: The cohort comprised of 20,967 women, 8,003 diagnosed with BD and 12,964 diagnosed with ES. In total, 266 females developed PCOS during follow-up, of whom 160 had been exposed to valproate. In the main analysis, current cumulative exposure was strongly associated with PCOS, with HRRs rising from 4.43, 95%CI:3.42-5.73 (0-90 DDDs) to 7.08, 95%CI:3.85-13.03 (> 365 DDDs), P < 0.001. In the never/ever analysis, valproate exposure was also associated with increased PCOS risk (HRR 1.55, 95%CI:1.20-2.00). By contrast, overall cumulative exposure showed a less consistent pattern, with risk most clearly elevated in the highest dosage category (> 365 DDDs, HRR 2.04, 95%:CI 1.28-3.20), p < 0.01.

Conclusions: Valproate exposure was associated with an increased risk of PCOS. The risk was especially pronounced during current and cumulative exposure, whereas overall cumulative exposure suggested increased risk at higher thresholds. These findings suggest that PCOS risk may be driven by acute pharmacological effects, although long-term cumulative use may also contribute. The results reinforce recommendations to avoid valproate in women of reproductive age when possible.

Background: Although bipolar disorder (BD) typically emerges in young adulthood, several studies have suggested that the onset of this disorder can occur later in life. However, there are hardly any studies that have established the incidence of BD in older ages and compared clinical features between later-onset and earlier-onset BD. Our study aimed to (1) assess the incidence rate of BD in a population-based prospective study of people older than 35 years, (2) clinically characterize these people with incident BD, and (3) compare their sociodemographic and clinical characteristics with those of people who had already reported lifetime BD at baseline.

Methods: We included 3,709 participants from a population-based cohort study aged 35 to 75 years at the first psychiatric evaluation (mean age 51.4 years, 54.1% women) with at least two psychiatric evaluations. Those exempt from BD at baseline were followed-up (mean duration 11.3 years) to assess the incidence rate of BD. Diagnostic criteria for mental disorders were elicited according to the DSM-IV using the semi-structured Diagnostic Interview for Genetic Studies.

Results: At baseline, 94 participants already met lifetime criteria for BD, whereas five developed BD during the follow-up, corresponding to an incidence rate of 12.2 per 100,000 person-years. Participants who developed BD during the follow-up had a substantially older age at the first episode compared to those who had already reported lifetime BD at the initial psychiatric evaluation (49.8 vs. 29.0 years, respectively). Those with incident BD also reported more frequent initial episodes with mixed symptoms (p = 0.003), a shorter duration of initial episodes (p = 0.005) and a higher prevalence of pre-existing or co-occurring illicit drug use disorders (p = 0.039) than those with pre-existing BD.

Conclusions: Although our results support a later emergence of BD in middle-aged adults, they also suggest atypical first manifestations of this later disorder with a high proportion of mixed episodes and high comorbidity with drug use disorders. From a clinical point of view, our data highlight the necessity for a thorough screening for first manifestations of BD also in middle-aged people particularly in the presence of drug misuse, which may delay the earlier recognition of mood episodes.

Background: Bipolar disorders (BD) are severe mental illnesses with recurrent depressive and (hypo-)manic episodes and a chronic course. While anecdotal and cross-sectional studies suggest a link between BD and creativity, longitudinal evidence is limited. This study investigates the role of creativity in individuals with varying risk for developing BD, using data from the multicenter, prospective Early-BipoLife study. N = 1,255 individuals aged 15-35 years were assessed and followed for over two years. Of these, N = 1,105 were included in the analyses; 150 were excluded due to missing creativity questionnaires. Creativity was measured with the Barron-Welsh Art Scale (BWAS) and the Creative Achievement Questionnaire (CAQ); BD risk was assessed with the EPIbipolar. Analyses included comparisons of mean creativity scores across BD risk groups and logistic regressions testing prospective associations between continuous creativity scores and transition to manifest BD. To enhance clinical applicability, group comparisons and odds ratios (ORs) were also calculated, providing estimates of relative risk across subgroups defined by BD risk status and creativity level.

Results: At baseline (BL), participants at high BD risk scored significantly higher on the CAQ than those at low risk, while no differences were observed for BWAS scores. During FU, 25 of 1,105 individuals transitioned to manifest BD. Logistic regression analyses did not reveal significant associations between creativity and transitions. However, group comparisons indicated elevated transition likelihood in individuals with high BD risk, with the highest ORs in those combining high BD risk and high creativity (BWAS: OR = 7.05, 95% CI: 1.94-25.56; CAQ: OR = 5.57, 95% CI: 1.88-16.54) compared to low-risk individuals with low creativity.

Conclusions: High BD risk was associated with higher CAQ scores at BL, suggesting heightened creativity may precede transition. Prospective analyses over two years did not confirm this association, likely due to the small number of transitions. Nonetheless, cross-sectional differences and group comparisons suggest that individuals with both high BD risk and high creativity, particularly real-world accomplishments captured by the CAQ, may show an increased likelihood of transition. These preliminary findings warrant replication in larger, longer-term studies. Importantly, creativity should not be pathologized but considered both as a resource and as a potential modifier of risk trajectories.

Bipolar Disorder (BD) is a highly complex and heterogeneous disorder. As such, accurate diagnosis is often delayed, and effective treatment options are limited. The Integrated Network, a program of Breakthrough Discoveries for thriving with Bipolar Disorder (BD²), was designed as a platform for longitudinal deep phenotyping of a diverse group of people with bipolar disorder to define disease trajectories and to gain insight into the biological drivers of the illness. Biosamples, including whole blood, serum, plasma, and peripheral blood mononuclear cells (PBMCs), will be collected longitudinally and will also be made available. The Integrated Network is designed to be the largest and most comprehensive prospective longitudinal study conducted in bipolar disorder, allowing for the development of precision-based treatment strategies that optimize quality of life for people living with bipolar disorder.

Bipolar disorder (BD) is a highly heritable mental illness that affects ∼ 1-2% of the world's population and has complex genetic and environmental underpinnings. Early detection is critical to improving treatment outcomes, but current strategies have limited predictive power. Early detection tools such as the Early Phase Inventory for Bipolar Disorder (EPIbipolar) and the Bipolar At-Risk (BARS) criteria assess phenotypic risk factors, including family history (FH) and subthreshold mood problems. Polygenic risk scores (PRS) are a quantitative metric of genetic susceptibility. This study examined the associations between BD-PRS and screening tools in order to assess their combined potential to identify individuals at risk of BD with improved predictive accuracy. The analysis included 1068 participants, including 199 at-risk young adults aged 15 to 35 years and 869 healthy controls aged 18 to 50 years. All of them had no prior psychiatric disorders. Inclusion criteria for the at-risk group comprised a positive FH (1st or 2nd degree) for BD, major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD), or the presence of specific BD risk factors (e.g., subthreshold hypomanic symptoms, mood swings, or sleep disturbances). Participants who had a confirmed BD, schizophrenia, schizoaffective disorder diagnosis, or other psychiatric conditions that could explain the symptomatology, were excluded. Diagnostic assessments that were utilized validated early detection instruments, including EPIbipolar, Bipolar Prodrome Interview and Symptom Scale-Prospective (BPSS-FP), and BARS criteria. Binary logistic regression models were employed to assess associations between BD-PRS and phenotypic risk markers, with adjustments for population stratification. Results revealed significant associations between BD-PRS and BARS criteria risk groups and EPIbipolar "at risk" criteria compared to controls. Significant associations were also identified for subscales including FH for BD, MDD, or schizophrenia, sleep and circadian rhythm disturbances, depressive characteristics, functional impairment, and episodic course. However, no significant associations were observed between BD-PRS and BPSS-FP, which highlights variability in the sensitivity of different early detection instruments. Our findings emphasize the potential of combining genetic susceptibility measures with phenotypic risk markers to enhance early detection strategies for BD. Further research is needed to optimize predictive models and evaluate the clinical utility of PRS in early intervention frameworks.

Background: Between major affective episodes some people with bipolar disorder experience persistent low mood or mood instability. Here we report an initial evaluation of the STABILISE programme (ISRCTN19416314; registration date 01.02.23), an adaptation of individual behavioural therapy that includes concepts and techniques addressing emotion regulation designed to support people experiencing these inter-episode symptoms. This study aimed to evaluate the safety, feasibility and acceptability of the intervention and to explore whether the pattern of clinical change had potential for the intervention to be of benefit. Twelve individuals with inter-episode bipolar symptoms received the STABILISE therapy in a randomised, multiple baseline case series. Participants were randomly assigned to wait 3, 4 or 5 weeks before commencing treatment, which comprised up to 22 sessions up to 7 months. Measures of symptoms, mood lability, recovery and quality of life were completed at intake, pre-therapy, and post therapy. Participants completed weekly measures of affective symptoms over the baseline and therapy periods, and for three weeks after.

Results: All 12 participants completed the therapy programme and reported high levels of satisfaction overall. No adverse events were judged to be therapy related. There was one instance of reliable deterioration on one outcome measure. Across all parameters of clinical change 9 of the 12 participants showed an overall pattern of improvement and none showed a pattern of deterioration overall.

Conclusions: This study provides preliminary support for the feasibility, acceptability, safety, and clinical potential of the STABILISE therapy. Further investigation of these aspects in a larger sample and within a randomised controlled trial design is required.

Background: Responsiveness to mood-stabilizing pharmacotherapy varies in bipolar disorder (BD). We investigated clinical correlates of second-generation antipsychotic (SGA) treatment response and conducted the first genome-wide association study (GWAS), including exploratory polygenic scores (PGS), of SGA pharmacogenomic treatment response in BD.

Methods: Treatment response was quantified using the Alda scale, and GWAS was performed using Alda-A score, controlling for sex, genotyping batch, and the genomic principal components.

Results: The cohort included 2,159 adults with BD (1,416 BD-I, 691 BD-II, 51 schizoaffective BD), mean age 41.8 years, 62% female, 84% white, and 14% Hispanic. Nearly half (48%) were treated with SGAs. Current SGA users were younger (41.2 ± 14.7 vs. 42.5 ± 15.3 years, p = 0.040), more likely to be Hispanic (14% vs. 11%, p = 0.047), had a higher body mass index (BMI; 30.4 ± 7.6 vs. 29.5 ± 7.1 kg/m², p = 0.005). Lifetime comorbidity patterns for current SGA users include higher rates of manic psychosis (29% vs. 17%, p < 0.001) and eating disorders - Anorexia Nervosa (7% vs. 4%, p = 0.003), Bulimia Nervosa (7% vs. 4%, p = 0.003), and Binge Eating Disorder (14% vs. 11%, p = 0.030). We detected a genome-wide significant association between SGA Alda-A scores and GAS7 variants (top variant: rs202127418, β=-2.998, p = 4.96E-08). However, SGA response was not significantly associated with PGS for schizophrenia, BD, and major depression (FDR > 0.05).

Conclusions: SGAs are frequently utilized as mood stabilizers in patients with BD and are associated with manic psychosis and eating disorders. GAS7 variants may predict SGA response, but larger, more diverse cohorts are needed for validation.

Background: There is emerging evidence that negative symptoms are a source of functional impairment for individuals with bipolar I disorder (BD). Patients with BD may also demonstrate notable changes in the perception of pain. The objective of this preliminary study was to explore potential associations between negative symptom severity and pain perception (measured with quantitative sensory testing (QST)) in BD as well as identify neurobiological correlates of these two domains.

Results: In patients with BD (N = 24, 30.3 ± 9.4 years of age), the Clinical Assessment Interview for Negative Symptoms (CAINS) Total and CAINS Motivation and Pleasure (MAP) subscale scores were associated with cold pain detection thresholds (CAINS Total: ρ = -0.49, p_UNC = 0.02, p_FDR = 0.09; CAINS MAP: ρ = -0.61, p_UNC = 0.003, p_FDR = 0.047; controlled for chlorpromazine (CPZ)-equivalent dose and Montgomery-Åsberg Depression Rating Scale (MADRS) scores). Parallel findings were observed for heat pain detection thresholds (CAINS Total: Spearman's ρ = 0.55, p_UNC = 0.009, p_FDR = 0.057; CAINS MAP: ρ = 0.54, p_UNC = 0.01, p_FDR = 0.057). Associations among CAINS expression scores and any QST-based measure less robust. An advanced multi-tensor model of crossing fibers was used to analyze Diffusion Tensor Imaging (DTI) data (N = 20). Here, the fractional anisotropy (FA) of the superior longitudinal fasciculus I (SLF-I), a white matter pathway integrating sensorimotor (Brodmann areas 5 and 7), parietal, and frontal cortices was associated with negative symptom severity (CAINS Total: ρ = -0.55, p_UNC = 0.019, p_FDR = 0.09; CAINS MAP: ρ = -0.56, p_UNC = 0.016; p_FDR = 0.09). A slightly more moderate trend between the FA of SLF-I and heat pain detection thresholds (ρ = -0.48, p_UNC = 0.044; p_FDR = 0.26) and heat pain tolerances (ρ = -0.53, p_UNC = 0.022; p_FDR = 0.26) was observed.

Conclusion: This preliminary study points to the relationship among negative symptom severity and the perception of pain in adults with BD. These findings suggest that thermal pain hypoalgesia in patients with BD may serve as a behavioral marker of negative symptoms, particularly in the MAP domain, potentially reflecting disruptions in sensory-affective integration. Further research with larger samples is warranted to clarify underlying neurobehavioral mechanisms.

Background: Recurrent course and disruption of circadian rhythms are among the core features of bipolar disorder (BD). Thus, ongoing symptom monitoring is an essential part of good clinical management.

Objective: We conducted a study to validate the English version of the ASERT (Aktibipo questionnaire), a tool for self-assessment of mood symptoms. We also analyzed the relationship of self-assessed symptoms with clinician ratings and actigraphy measures, and investigated the possibility of predicting depressive episodes using subjective and digital measures.

Methods: This was a longitudinal study of twenty individuals with BD, followed for up to 11 months. The participants completed weekly mood self-assessments (ASERT) using a smartphone app and wore wrist actigraphs. During monthly appointments, the severity of their mood symptoms was rated by clinicians, and the participants completed questionnaires addressing overall functioning (FAST), and biological rhythms (BRIAN).

Results: The study confirmed the validity and reliability of the ASERT as a measure of subjective mood. Additionally, we found significant associations between ASERT responses, clinical scales, and actigraphy data (ASERT_dep vs. MADRS β = 1.42, p < 0.001, ASERT_man vs. YMRS β = 0.38, p < 0.001, mixed-effect model). In our analysis, a combination of self-assessment and actigraphy data detected depression relapse with 67% sensitivity, 90% specificity, 81% balanced accuracy, and AUC of 0.80. Furthermore, we observed a strong correlation between the actigraphy-derived interdaily stability and BRIAN scores (β=-3.86, p = 0.005) overall functioning, emphasizing the significance of circadian rhythm disruptions in BD.

Conclusion: This study highlights the potential of digital tools, such as digitally administered self-assessments and actigraphy, to enhance the management of BD by providing valuable insights into mood states and detecting relapse. Further research is needed to refine and optimize these tools for widespread clinical application, such as informing personalized treatment plans.

Background: Pharmacological treatment for mental illness can paradoxically compromise physical health, with weight gain and related cardiovascular and metabolic diseases among its most concerning side effects. Understanding and mitigating the metabolic consequences of antipsychotic and mood stabilizing treatments is therefore crucial for improving long-term health outcomes in individuals with severe mental illness such as schizophrenia and bipolar disorder. This literature review focuses on the underlying mechanisms linking antipsychotics and mood stabilizers to weight gain in bipolar disorder. Current evidence on both pharmacologic and nonpharmacologic strategies to prevent this side effect is also addressed.

Methods: A literature search was conducted from February-April 2025 using PubMed and Google Scholar. The electronic search was complemented by a manual search for additional articles in reference lists and previous reviews. Relevant reviews, cohort studies, meta-analyses and randomized controlled trials (RCTs) were reviewed.

Results: Our results support that different mood stabilizers and antipsychotics contribute to weight gain through distinct biological mechanisms, including metabolic dysregulation, appetite modulation, and hormonal changes. Nonpharmacologic interventions, such as dietary modifications, physical activity, cognitive and behavioral strategies, play a crucial role in counteracting medication-induced weight gain. Pharmacologic approaches, including adjunctive medications, offer potential in mitigating weight gain, but their effectiveness and safety profiles require further evaluation.

Conclusion: Customized treatment plans tailored to each patient's needs, preferences, goals and circumstances should be considered for the treatment of antipsychotic and mood stabilizer-associated weight gain.