OBJECTIVE:The Rapid Mood Screener (RMS) is a reliable and validated brief, point-of-care, patient-administered screening tool for bipolar disorders. Herein we aim to evaluate the reliability and validity of the RMS in Turkish adults with bipolar I disorder (BD). METHOD:Forward and backward translation was conducted for the English version of the RMS to the Turkish version of RMS (RMS-T). We conducted a ROC analysis for both the Mood Disorder Questionnaire (MDQ) and RMS-T in adults with major depressive disorder (MDD) or BD. The maximum sensitivity and specificity were also calculated. RESULTS:We recruited 128 participants (n = 63 BD-I, n = 65 MDD). Participants who responded 4 or more "yes" out of six items on the RMS-T were adjudicated as a positive screen for BD-I. The sensitivity of the RMS-T was 79.4% and the specificity was 84.6%. The RMS-T was determined to be of higher discriminative power in discriminating BD relative to the MDQ (AUC = 0.865, p < 0.001). CONCLUSION:The RMS-T is a valid and easy-to-use self-administer tool for the identification of BD-I in individuals with depression. The RMS has many advantages over the MDQ in clinical settings by having fewer items, a simpler scoring system, and shorter completion time. Early screening and detection of BD is critical for appropriate treatment selection to achieve the goal of overall improving health outcomes.
OBJECTIVES:Treatment-resistant depression poses substantial clinical challenges, particularly following multiple unsuccessful pharmacologic treatments. This brief report considers the role of hope as a therapeutic imperative in the management of treatment-resistant depression. METHODS:The case presented by Malhi and colleagues is considered in relation to established approaches to staging treatment resistance and the broader humanistic dimensions of caring for patients with chronic and refractory illness. RESULTS:Existing staging systems can help characterize the extent of treatment resistance and support a systematic approach to management but do not fully capture these humanistic dimensions. Hope extends beyond simple optimism to encompass a realistic belief in the possibility of meaningful improvement despite previous treatment failures. Clinicians can foster hope by clarifying patients' goals, identifying attainable improvements in quality of life and functioning, and reinforcing agency and purpose alongside continued multidisciplinary treatment. CONCLUSIONS:Treatment resistance should not be equated with irremediability; hope is an integral component of person-centred psychiatric care.
OBJECTIVES:Sleep disturbances are common in individuals with bipolar disorder (BD) and are linked to greater symptom severity, higher relapse risk, and increased suicidality. Despite their clinical relevance, sleep problems in BD are frequently underdiagnosed and inadequately treated. This systematic review aimed to evaluate the efficacy and safety of pharmacological and non-pharmacological interventions specifically targeting sleep disturbances in BD. METHODS:We systematically searched PubMed, Embase, Web of Science, and PsycINFO for studies published until May 2025. Inclusion criteria encompassed randomized controlled trials and observational studies assessing interventions specifically targeting sleep disturbances in individuals with BD. RESULTS:Eleven studies met the inclusion criteria. Non-pharmacological interventions, particularly cognitive behavioral therapy for insomnia adapted for bipolar disorder (CBTI-BD), consistently improved sleep efficiency, latency, and total sleep time and were associated with reductions in depressive symptoms. Bright light therapy yielded mixed results, whereas the Benson Relaxation Technique showed improvements in sleep quality and emotional regulation. Among pharmacological approaches, melatonin improved circadian alignment and sleep parameters without mood destabilization. Suvorexant showed limited efficacy. Antidepressants were linked to poorer sleep quality and greater impulsivity during euthymia. CONCLUSIONS:Sleep-focused interventions, especially behavioral strategies such as CBTI-BD, appear effective and well tolerated for managing sleep disturbances in BD, primarily in euthymic and interepisode samples where they have been tested. Pharmacological interventions show more variable effects and require careful attention to tolerability and clinical stability. Because each intervention was evaluated in a single clinical phase, the available evidence cannot determine whether clinical phase or chronotype moderates treatment response; trials designed to detect such moderation are needed before individualized, phase-specific recommendations can be made.
OBJECTIVES:To contextualize the real-world findings of repeated intravenous ketamine infusions for treatment-resistant bipolar depression (TRBPD) and identify priorities for safer, more durable clinical implementation. METHODS:We provide a focused commentary on Zhou et al. (2023) and integrate selected evidence concerning inflammatory and metabolic correlates, neurocognitive outcomes, and continuation-phase ketamine treatment. RESULTS:Repeated subanesthetic ketamine infusions may rapidly improve depressive and anxiety symptoms with an acceptable short-term safety profile. However, the predictive value of C-reactive protein and body mass index varies across cohorts; available cognitive findings are reassuring but limited; and relapse after induction highlights the need for individualized maintenance planning. CONCLUSIONS:Ketamine pathways for TRBPD should combine cautious patient stratification, repeatable cognitive monitoring, and explicit continuation or booster strategies. Prospective bipolar-specific studies are needed to clarify predictors, durability, and stopping rules.
OBJECTIVES:To investigate pharmacological treatment patterns in individuals with bipolar disorder (BD) with and without comorbid substance use disorder (SUD) and anxiety disorder (AX), we leveraged the Global Bipolar Cohort to analyze cross-regional practices across North America, Europe, and the Pacific. METHODS:Fourteen cohorts contributed aggregate data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities. Proportional meta-analyses using generalized linear mixed models were conducted to examine prescription trends and identify clinical differences. RESULTS:The sample (N = 11,521) was 60% female and 84% Caucasian. Participants were categorized into four mutually exclusive groups based on comorbidity status: those with comorbid AX only, comorbid SUD only, both AX and SUD, or neither. The AX+SUD subgroup showed higher rates of attention-deficit/hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), rapid cycling, obesity, and unemployment, reflecting a more severe clinical profile. Regional variations were notable: North American cohorts reported higher prevalence of AX and SUD than European and Pacific cohorts. Antidepressants use for AX were more common in Europe and the Pacific, while North American prescribing patterns were more variable. Benzodiazepine use was high among individuals with SUD across all regions. Lithium and first-generation antipsychotic prescriptions varied, with higher rates observed in Europe. CONCLUSIONS:Findings underscore the heterogeneity of BD and the influence of comorbid AX and SUD on illness burden and treatment. Regional prescribing variations underscore the need for context-specific guidelines. Gaps in data on medication-assisted treatment for SUD point to areas for future research. These insights can support more individualized and effective care for complex BD presentations.
INTRODUCTION:This cross-sectional descriptive study aims to examine the relationship between perceived social support, treatment adherence and recovery in individuals diagnosed with bipolar disorder. The impact of social support elements, especially family, friend and special person support, on the treatment adherence and recovery are evaluated. METHODS:105 individuals diagnosed with bipolar disorder participated in the study. Data were collected using the Multidimensional Perceived Social Support Scale (MSPSS), Morisky Medication Adherence Scale (MMAS) and Recovery Assessment Scale (RAS). The obtained data were evaluated using the SPSS program. RESULTS:Analysis showed a significant and positive relationship between perceived social support and recovery levels (p < 0.05). It was determined that family support, in particular, significantly increases treatment adherence and contributes positively to the recovery process. It was also determined that the RAS sub-dimensions of hope, help, success, trust and coping levels were in a strong relationship with social support. Moreover, perceived social support has consistently been identified as a significant predictor of recovery. DISCUSSION:Study findings reveal that social support is of critical importance in the treatment of bipolar disorder. In particular, strengthening family support can positively affect treatment adherence and the recovery process. These results emphasize that the effective use of social support systems should be considered a key element in treatment planning. By demonstrating this relationship, the study provides a valuable basis for future investigations that may further clarify how social support can be systematically leveraged to improve treatment effectiveness.
BACKGROUND:Older adults with bipolar disorder (BD) are at high risk for severe mood symptoms, cognitive difficulties, and early mortality; however, underlying brain alterations have received little study. Gray matter decreases in ventral prefrontal cortex (VPFC) seen in younger persons with BD, and additionally in dorsal PFC (DPFC), are implicated. Here, cortical thickness was examined in an international sample. METHODS:Cortical thickness in 34 regions was measured from structural magnetic resonance imaging data using enhancing neuroImaging genetics through meta-analysis pipelines for individuals with BD (n = 308) and non-psychiatric comparison participants (n = 287), ages 40-70y, from six Global Aging and Geriatric Experiments in BD (GAGE-BD) consortium sites. Group differences were assessed for VPFC, DPFC and remaining cortical regions, covarying for scanner, age and sex. Results were considered significant corrected for false discovery fate (FDR) at pFDR < 0.05. Relationships with demographic and clinical factors were explored. RESULTS:Cortical thickness was significantly lower among BD in VPFC and DPFC, and additional distributed regions (pFDR < 0.05) and negatively associated with age (p < 0.05); group and age did not interact significantly. Relationships with BD subtype and medications were observed; lithium was associated with higher frontal pole and anterior cingulate thickness (pFDR < 0.05). CONCLUSIONS:In this international middle and older aged adult BD sample, lower VPFC cortical thickness was observed, suggesting these deficits persist from younger age. DPFC and additional regions of reduced cortical thickness could contribute to the older adult BD phenotype. Cortical thinning was more pronounced among older individuals regardless of diagnosis. Lithium may lessen cortical thinning.
BACKGROUND:Higher time in sedentary behavior and insufficient physical activity are very common in bipolar disorder (BD). Whereas physical activity and exercise offer significant benefits across mental health, brain health, and heart health in BD. The International Society for Bipolar Disorders Nutrition and Exercise Task Force (NExT) synthesized evidence to evaluate the impacts of sedentary behavior, physical activity, and exercise on illness course, physical health, and treatment outcomes. METHODS:A best-evidence synthesis was conducted using a question-and-answer format. We searched PsycINFO, SPORTDiscus, Embase, PubMed, and Web of Science from inception to March 1st, 2026, supplemented by reference lists and existing guidelines. Search terms included combinations of physical activity, exercise, sedentary behavior, and bipolar disorder-related terms. RESULTS:Observational studies show that individuals with BD exhibit significantly higher sedentary behavior and lower physical activity compared to the general population, with notable discrepancies between self-reported and objective measurements. Evidence on physical activity's protective role against BD onset is mixed, with some prospective and Mendelian randomization studies suggesting reduced risk, while others report bidirectional or null associations. Preliminary findings from clinical trials indicate that exercise improves overall functioning, reduces mood episode frequency and hospitalizations, and alleviates depressive symptoms, with one pilot study showing an 82% antidepressant response rate. Exercise also shows potential to reduce anxiety and improve sleep, though robust data are limited. CONCLUSIONS:Despite limited high-quality evidence, physical activity and exercise demonstrate promising physical and mental health benefits for individuals with BD. Future research should prioritize multicenter randomized controlled trials, enhanced assessment tools, and accessible, tailored programs to integrate physical activity into routine BD management.
BACKGROUND:Induced pluripotent stem cell (iPSC)-derived brain cells are widely utilised as in vitro models for several neuropsychiatric disorders, as they retain the donor's genetic profile, offering a unique opportunity to study living human brain cells and perform controlled experimental manipulations. In this study, we conducted whole transcriptome sequencing of cortical networks (co-cultures of neurons and astrocytes) derived from 12 participants with bipolar disorder (BD) and 12 participants without a history of mental health disorders. Aiming to identify new molecular mechanisms underlying the pathophysiology of bipolar disorder. METHODS:iPSCs were generated by reprogramming peripheral blood mononuclear cells (PBMCs) using episomal vectors. iPSCs were then differentiated into neural progenitor cells (NPCs) and matured into cortical networks (CNs) that express markers of neurons and astrocytes. Whole transcriptome data were obtained using the Illumina NovaSeq X sequencing platform. Differential expression analysis was performed using DESeq2 in R. RESULTS:Gene set enrichment analysis identified 191 enriched pathways in BD, 171 were downregulated, and around 10% were associated with the immune system. Of these, the toll-like signalling pathway, which is downregulated in BD, was further investigated. CONCLUSION:Our results suggest a profound immune dysregulation in BD, with downregulation of the sensing innate immune system, particularly highlighting the immune system's role as a complex signalling network.
BACKGROUND:Aberrant thalamic structure has been documented in youth with bipolar disorder (BD) and linked with cannabis use, which commonly co-occurs with BD. However, the timeline of when these associations evolve remains unclear. This study aimed to longitudinally compare thalamic volume among youth with and without first episode mania who do or do not use cannabis and other substances. METHODS:Demographic and magnetic resonance imaging (MRI) data from youth (13-18 years old) with BD (n = 22) were compared to similarly aged healthy youth (n = 23) at baseline and 12-month follow-up. Clinical group status, including BD and substance misuse and dependence, was evaluated using semistructured interviews. Multivariate analyses accounting for total brain volume and baseline age were conducted to evaluate baseline and longitudinal group differences in thalamic volume. RESULTS:At 12 months, BD youth had significantly smaller left thalamus volumes compared to healthy youth (p = 0.009). Lifetime cannabis use was associated with smaller left thalamus volumes for all youth (p < 0.001) and for youth with BD compared to healthy controls (p < 0.001) across time. Among BD youth, co-occurring lifetime substance use was associated with significant volumetric reductions in the left thalamus from baseline to follow-up (p = 0.004), but not among healthy youth (p = 0.517). No significant group differences or changes were observed in the right thalamus. CONCLUSIONS:BD is associated with smaller left thalamic volume after the first manic episode. Cannabis use may compound thalamic volume reductions in youth with BD. Investigations with larger sample sizes are needed to replicate these findings and examine clinical correlates of cannabis use alongside long-term thalamic trajectories.
INTRODUCTION:The prevalence of tobacco smoking and high nicotine dependence (ND) in bipolar disorder (BD) is higher than in the general population but lower than in schizophrenia. This study aims to analyse the relationship of smoking behaviours, including age at onset of daily smoking (AODS), with age at onset of BD and course-of-illness variables -particularly recurrent suicide attempt- in a community sample of BD patients, also compared in their smoking behaviour variables with a sample of non-psychiatric adults. METHODS:Samples of 108 patients with BD and 290 non-psychiatric adults were compared in their smoking habit. High ND was defined by a score of ≥ 6 on the Fagerström Test for Nicotine Dependence. Logistic regression analyses were employed to identify factors associated with daily smoking and high ND. Hazard curves were used to compare AODS between patients and controls and, among patients, age of BD onset between smokers and non-smokers. Within-subject survival times -AODS and the age at onset of BD symptoms- were compared with a multi-state illness-death model. RESULTS:Compared with controls, BD patients showed higher prevalences of current daily smoking (44% vs. 34%) and high ND (25% vs. 9%); and lower smoking cessation rates (23% vs. 38%). Among BD patients, recurrent suicide attempt showed a strong independent association with both daily smoking and high ND. AODS was later in BD patients than the control group. Among patients, illness onset was earlier in smokers and AODS was earlier than illness onset. CONCLUSION:Addressing tobacco consumption should be an integral component of BD prevention and treatment strategies.
INTRODUCTION:Mood and/or affective instability and circadian rhythm disruptions are increasingly recognised in psychiatric disorders, notably bipolar disorder (BD), but their interrelationship remains unclear. By definition, both have an integral temporal component and, as such, measuring them longitudinally and remotely is desirable. METHODS:We assessed the feasibility and value of digital devices to capture mood and subjective state (affect) instability and daily rest-activity patterns over a 10-week period in two groups of participants. The first group (n = 37) scored > 7 on the Mood Disorder Questionnaire (MDQ) ('high MDQ'), indicating a history of mood elevation and increased risk for BD. They were compared with a group (n = 37) scoring < 5 on the MDQ ('low MDQ'). Over the 10-week period, mood was rated daily, clinical ratings of depression, mania and anxiety were captured weekly, and a GENEActiv actigraph was worn to collect rest-activity pattern data. RESULTS:The main findings were that (1) MDQ score predicted instability in mood and subjective state; (2) high MDQ score was associated with greater negative affect, mood symptoms and altered circadian activity profiles compared with low MDQ; and (3) mood and subjective state instability appeared unrelated to circadian indices. CONCLUSION:These findings suggest that (1) remote monitoring of these domains is feasible and valuable; (2) selection of participants based on MDQ score is useful for studying mood and affective instability; and (3) this approach has potential utility for clinical and experimental medicine studies assessing interventions targeting mood dysregulation and affective instability.
OBJECTIVES:Lithium is recommended as the first-line maintenance treatment for older adults with bipolar disorder (OABD). However, age-related reduction in renal clearance, heightened sensitivity to adverse effects, and drug interactions increase the risk of toxicity and necessitate lower therapeutic serum levels in this population. Despite expert consensus supporting age-adjusted targets, most clinical laboratories still do not report age-specific therapeutic ranges. We conducted a systematic review on recommended serum lithium levels in OABD to update evidence supporting age-specific therapeutic ranges for safe and effective lithium management. METHODS:We searched Medline, PsycINFO, Embase, and Cochrane Central Register of Controlled Trials since 2017 for studies analyzing lithium serum levels in individuals with bipolar disorder ≥ 60 years. Two reviewers independently screened titles, abstracts, and full texts. We used the National Institutes of Health Quality Assessment Tool to assess methodological quality. RESULTS:Fourteen studies, including 8808 older adults using lithium, met inclusion criteria. All studies were observational with cross-sectional or cohort designs. Mean or median lithium levels ranged from 0.47-0.67 mmol/L. Levels of 0.82-1.00 mmol/L were associated with increased side effects or early toxicity signs, while levels of 1.20-1.25 mmol/L were overtly toxic. Impaired renal function and concomitant use of diuretics, ACE inhibitors, and NSAIDs required closer monitoring for toxicity. CONCLUSIONS:These findings are consistent with age-adjusted lithium therapeutic targets in older adults and provide additional observational support for clinical laboratories to adopt age-specific therapeutic ranges. Clinicians should consider individualized monitoring accounting for age-related physiological changes and medication interactions to ensure safer and effective lithium therapy.
BACKGROUND:Epigenetic age accelerations have been associated with the clinical expression of BD; however, with few available studies. METHOD:We calculated Horvath, Hannum, EN, GrimAge, and PhenoAge epigenetic ages in a sample of 139 individuals with BD. We used a latent profile analysis to identify subgroups of individuals based on their profile of epigenetic age accelerations. We compared these profiles for socio-demographic characteristics, course of BD, associated psychiatric conditions, current medication use, telomere length, mitochondrial DNA copy number (mtDNAcn), markers of metabolic syndrome, and of systemic inflammation. RESULTS:The latent profile analysis identified two subgroups, one with accelerated and one with decelerated epigenetic aging (respectively 58% and 42%). Subgroups did not differ for socio-demographic characteristics, course of BD, associated psychiatric conditions, nor current medication use. The accelerated aging subgroup was characterized by higher depressive symptoms (p < 0.001), lower mtDNAcn (p < 0.001), higher levels of systemic inflammation (platelet/neutrophil ratio, neutrophil/lymphocyte ratio, systemic inflammation index, p < 0.001) that remained significant after correction for multiple testing. Some associations with anxiety symptoms, social functioning, blood pressure, and waist circumference did not remain significant after correction for multiple testing. CONCLUSIONS:Most individuals with BD were characterized by an accelerated epigenetic age profile. This study suggests a link between epigenetic age acceleration, systemic inflammation, and mtDNAcn. This subgroup might represent a target for personalized prevention and treatment.
OBJECTIVE:Systematically collected pregnancy safety data for cariprazine have been lacking, despite growing use of this medication across psychiatric indications. The goal of this analysis was to determine the risk of major malformations among infants of mothers with psychiatric illness who used cariprazine during the first trimester of pregnancy compared to unexposed controls. METHODS:The National Pregnancy Registry for Psychiatric Medications (NPRPM) is a prospective pharmacovigilance program in which pregnant women with psychiatric diagnoses are enrolled during pregnancy and followed through the postpartum period. Labor and delivery and pediatric medical records are reviewed for evidence of major malformations followed by final adjudication by a dysmorphologist blinded to medication exposure. Infants with first-trimester exposure to cariprazine were compared to controls not exposed to second-generation antipsychotic medications. RESULTS:As of September 9, 2025, N = 4,125 have enrolled in the study. Of those enrolled, 58 cariprazine-exposed infants and 2,098 infants in the comparison group were eligible for inclusion in this analysis. There were no major malformations in the cariprazine-exposed group (absolute risk 0.00%; 95% confidence interval, 0.00%-6.16%) compared to 32 infants with major malformations in the control group (1.53%; 1.05%-2.15%). CONCLUSIONS:In this prospective cohort, 0 of 58 infants exposed to cariprazine during the first trimester had major malformations, compared with 32 of 2,098 (1.53%) unexposed infants. Although these data are preliminary and cannot rule out modest teratogenic effects, they are nonetheless important to provide to health care providers and the public, as cariprazine use has been rising among women of reproductive age.
