International Journal of Bipolar Disorders最新文献

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.

Background: Perinatal bipolar disorder (BD) presents unique challenges due to physiological, hormonal, and psychosocial changes during pregnancy and postpartum, increasing vulnerability to mood instability. Effective management is vital for maternal and infant health, but multiple barriers complicate care. This review aims to clarify whether obstacles arise from limited psychiatric expertise among obstetric providers, insufficient perinatal knowledge among psychiatric providers, or both.

Methods: A thematic review was conducted following PRISMA guidelines, synthesizing literature (2015-2025) from major databases and clinical guidelines on barriers and solutions in perinatal BD management. Both qualitative and quantitative studies were included. Data extraction, quality assessment, and thematic analysis were performed by multiple independent reviewers.

Results: Four major barriers were identified: (i) Diagnostic challenges-obstetric providers may miss or misdiagnose BD due to symptom overlap with normal perinatal changes, while psychiatric providers may lack specific perinatal expertise; (ii) Treatment issues-concerns about medication safety, particularly among obstetricians, and limited access to specialized psychiatric care, leading to increased relapse risk; (iii) Psychosocial barriers-stigma, inadequate support, and new maternal responsibilities hinder help-seeking; (iv) Poor interprofessional communication-fragmented care often results when obstetric and psychiatric providers lack coordination. These barriers adversely impact both mothers and infants, increasing relapse rates and impairing mother-infant bonding. Proposed solutions include improved diagnostic training for both provider types, integrated care models, enhanced patient education, support systems, and policy reforms. However, there remain knowledge gaps regarding long-term outcomes and optimal screening.

Conclusions: Effective perinatal BD management requires multidisciplinary, individualized, and integrated care addressing both clinical and psychosocial barriers. Bridging knowledge gaps between obstetric and psychiatric providers through education, research, and policy reform is essential to improve outcomes for mothers and their families.

Offspring of parents with bipolar disorder (OBD) are at increased risk for mood and behavioral disorders, with emotional dysregulation being an early marker. This pilot study aimed to evaluate the effect of a family-focused intervention on emotional dysregulation in OBD, hypothesizing a significant reduction in CBCL Emotional Dysregulation Profile scores over 12 months. Twenty-five OBD aged 6-16 years participated in a four-session psychoeducational program. Significant reductions were observed in CBCL emotional dysregulation scores suggesting that a brief family-focused program may reduce dysregulation and improve functioning in OBD. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov. ID NCT03299140. Registered on the 17th September, 2017.

Background: To identify, appraise, and synthesise qualitative studies exploring the experiences of informal caregivers (unpaid individuals providing emotional and or practical care) supporting individuals diagnosed with bipolar disorder (BD), and to identify any emotional, practical, or informational needs.

Methods: Ovid, MEDLINE, Scopus, PsychINFO and CINAHL were searched from 1980 to January 2025. Studies were eligible for inclusion if they were peer viewed, published in English, used qualitative data collection and analysis, had data on the experiences of caregivers (aged 18 or above) supporting individuals with BD (aged 14 or above), and were conducted in western countries with individualistic cultures. Studies were appraised using the Critical Appraisal Skills Programme checklist. Data were analysed using thematic synthesis.

Findings: Fourteen papers were included in the review. Three analytical themes: 'challenges of caregiving', 'healthcare system challenges', and 'coping with the shifting landscape' were identified, encompassing six descriptive themes and three supporting subthemes.

Conclusions: Caregivers supporting individuals with BD face complex emotional and physical challenges, coupled with significant imposed losses and responsibilities. The relapsing and unpredictable nature of BD can exacerbate caregiver demands. There is a need for increased societal awareness of BD, improved communication and collaboration between mental health services and caregivers, and improved support for caregiver wellbeing. Further research exploring cultural, gender, and role specific needs of caregivers is warranted.

Background: Bipolar disorders (BD) pose significant therapeutic health challenges due to recurrent and largely unpredictable depressive and (hypo)manic episodes. Traditional self-report methods for symptom monitoring are limited by their dependence on patient adherence which is frequently diminished during symptomatic phases. Circadian movement patterns, measured via actigraphy, have emerged as promising digital biomarkers for distinguishing mood states in BD. This study examined the utility of circadian rhythm parameters in differentiating euthymic, depressive, and (hypo)manic states.

Methods: This study analyzed data from 27 BD patients (mean age = 46 years, 16 female) monitored over 12 months as part of the BipoSense project. Wrist-worn accelerometers continuously recorded physical activity, while mood state was assessed using daily self-reports and biweekly expert evaluations. Circadian rhythm parameters included interdaily stability (IS), intradaily variability (IV), mean activity difference (MeanDiff), and circadian form difference (FormDiff). IS and IV reflect rhythm stability and fragmentation, while MeanDiff and FormDiff quantify overall activity and deviations in circadian rhythm form. Multilevel models were used to predict categorical mood states (depressive, (hypo)manic, euthymic) and dimensional symptom severity.

Results: Physical activity data from 23 patients yielded 2,669 valid days for analysis. In multilevel logistic models, lower MeanDiff (B = -.02, P < .001), reflecting reduced overall activity, lower IS (B = -.80, P = .009), indicating less stable circadian rhythms, and higher FormDiff (B = .03, P < .001), denoting a more rigid circadian activity pattern, were significantly associated with increased odds of depressive days compared to euthymic days. Conversely, higher MeanDiff (B = .02, P = .007) was linked to higher odds of (hypo)manic days. Dimensional linear mixed models showed a similar pattern: lower MeanDiff (β = -.11, P < .001), IS (β = -.06, P = .001), and IV (β = -.06, P = .002), together with higher FormDiff (β = .10, P < .001), predicted increased depressive symptom levels. Conversely, higher MeanDiff (β = .10, P < .001), IS (β = .04, P = .024), IV (β = .07, P < .001), and lower FormDiff (β = -.07, P = .001) were associated with heightened (hypo)manic symptoms.

Conclusions: Circadian rhythm parameters can effectively differentiate mood states in BD, highlighting their potential as clinical markers for episode transitions. Although the study was explorative by nature, the findings emphasize the potential value of integrating circadian biomarkers into digital phenotyping for mood state monitoring. Future studies should explore extended monitoring periods, larger samples, and real-time feedback systems to improve early intervention and personalized treatment strategies in BD.

Background: Although lithium is considered the gold standard for the maintenance treatment of bipolar disorder (BD), its prescription has declined in recent decades. At the same time, second-generation antipsychotics (SGAs), such as quetiapine, and other mood stabilisers such as valproic acid, have been increasingly used. Social media platforms such as X (formerly Twitter) provide real-time insights into public and professional perceptions of these treatments, which may influence their use and adherence.

Aims: To analyse how lithium, quetiapine, and valproic acid have been represented on X, by focusing on user type, engagement levels, and thematic content of tweets.

Method: We conducted a mixed-methods, observational study of tweets published in English and Spanish between 2008 and 2022. Tweets containing the generic or commercial names of lithium, valproic acid, and quetiapine were retrieved and analysed using a validated codebook and semi-supervised machine-learning models. Tweets were categorised by user type and clinical and non-clinical content themes.

Results: Among the 236,797 analysed tweets, quetiapine was the most frequently mentioned drug (69.4%), followed by valproic acid (19.1%) and lithium (11.5%). Lithium tweets showed the highest engagement (54.0 likes and 18.0 retweets per tweet). Patients mainly focused on quetiapine (47.0%), while healthcare professionals more often discussed lithium (58.1%). Tweets containing clinical content were more common in English (78.0%) than in Spanish (54.7%), especially regarding side effects (53.1% vs 8.2%). Tweets on effectiveness were more frequently discussed in English (48.8%), especially for quetiapine (54.7%), but were less common in Spanish (9.8%). Discussion about drug shortages was more prevalent in Spanish tweets (31.6% vs 0.5%), particularly for valproic acid (55.8%).

Conclusions: Despite lithium being the least mentioned drug, it generated the highest level of engagement, particularly among healthcare professionals. In contrast, quetiapine was widely mentioned by patients, which reflects a more socially widespread and, at times, problematic use. These findings highlight the value of listening to conversations on social media to better understand perceptions, concerns, and attitudes that may influence adherence and prescribing trends in mental health.

Background: The postpartum period is a recognized high-risk phase for maternal and infant health, yet predictors of bipolar disorder (BD) recurrence during this period remain unclear, particularly regarding distinctions between BD type I and II. This retrospective observational study assessed rates and clinical correlates of postpartum mood episodes in 248 women with a history of at least one pregnancy, affected by BD I (n:89) and BD II (n: 159). Participants were divided into two groups based on the presence/absence of postpartum mood episodes. Due to non-normal data distribution (Shapiro-Wilk:0.925, p < 0.001; Kolmogorov-Smirnov:0.122, p < 0.001), group comparisons were performed using Pearson's χ² test for categorical variables and the Kruskal-Wallis test for continuous variables. Logistic regression was used to identify clinical variables associated with a history of postpartum mood episodes.

Results: Eighty-two patients (29.4%) in the overall sample had a history of postpartum mood episodes, with a higher prevalence in BD I than BD II (30.3% vs. 27.0%). A later age at BD onset was significantly associated with a lower risk of postpartum recurrences in both BD I (21.4% vs. 55.7%, p:0.010) and BD II (27.3% vs. 59.1%, p < 0.001). In BD I, women with peripartum episodes had an earlier age at menarche (36.0% vs. 10.0%, p:0.003). In BD II, those with peripartum recurrences showed an earlier age at first hospitalization (40.6 ± 13.0 vs. 51.0 ± 12.3 years, p:0.010) and higher rates of medical comorbidities (74.8% vs. 54.5%, p:0.013). Logistic regression analysis confirmed the associations observed between clinical variables and postpartum mood episode risk in both BD I and BD II subgroups.

Conclusion: These findings indicate that in BD I underlying inherited constitutional factors (as age at onset and age at menarche) may influence postpartum episode risk, whereas in BD II recurrence appears more related to illness severity (such as age at first hospitalization and medical comorbidities). Given the lack of established predictors for perinatal recurrences, further studies are warranted to validate and expand these findings, enhancing the understanding of mood recurrence risk during the postpartum period.