International Journal of Bipolar Disorders最新文献

Background: Oxytocin (OXT), a neuropeptide involved in social behaviors and emotions, exhibits bidirectional effects depending upon positive or negative environments. Our previous report highlighted dysregulation of OXT on striatocortical functional connectivity (FC) in bipolar disorder (BD) patients. We hypothesized that: (1) in healthy controls (HC), carriers of a "sensitive" OXTR allele would show altered FC, particularly in association with childhood trauma; and (2) this gene-brain relationship would be fundamentally altered or reversed in BD patients, reflecting a gene-disease interaction.

Method: Thirty-nine BD patients and 32 age-matched HC underwent resting-state functional MRI and blood sampling for genotyping and plasma OXT level assessment.

Results: BD patients, compared to HC, demonstrated elevated plasma OXT levels and higher scores in childhood trauma. Gene-disease interactions were observed in the striatocortical circuitry with OXTR rs53576 and rs2228485, with greater robustness in rs2228485. In HC, the rs2228485 AA homozygotes showed enhanced striatocortical FC with the sensory association and limbic areas, which were correlated with the childhood trauma. Conversely, alterations in ventral striatocortical FC were reversed among BD patients, with hypo-FC in AA homozygotes and hyper-FC in G-allele carriers.

Conclusions: These findings highlight a gene-disease interplay, suggesting that individuals carrying the "sensitive" allele may exhibit context-dependent alterations in salience-related brain networks. Our results identify a potential neural mechanism through which the OXTR polymorphism modulates environmental sensitivity, with distinct effects in HC and BD. Childhood trauma may shape striatocortical FC in an OXTR genotype-dependent manner.

Background: As choices of treatments for bipolar disorder types I (BD1) and II (BD2) and major depressive disorder (MDD) continue to evolve, we reviewed studies directly comparing current clinical usage rates of medicinal treatments for these disorders.

Methods: Comprehensive searching of five literature databases through March 2024 identified reports on clinical drug prescription rates for BD and MDD patients. Rates were summarized and compared by random-effects meta-analyses with R-Studio software.

Results: A total of 18 reports (2006-2023) supported comparisons of clinically prescribed treatments for 17,572 mood-disorder patients (mean age 42.8 years; 7936 BD1 age 43.2 years; 6309 BD2, age 43.3; 3327 MDD, age 40.0). Among diagnoses: (BD1 vs. BD2 vs. MDD), treatments differed as: lithium (54.4% vs. 38.0% vs. 6.78%), second-generation antipsychotics (41.6% vs. 22.3% vs. 15.9%), valproate (25.7% vs. 21.5%; no MDD data), lamotrigine (13.1% vs. 27.2%; no MDD data), and antidepressants (34.9% vs. 46.4% vs. 77.5%). International use of lithium for BD appeared to increase between 2006 and 2023.

Limitations: Outcomes were heterogeneous and requiring inclusion of lithium may introduce selection bias.

Conclusions: Clinical treatment selections for BD1, BD2, and MDD patients differed substantially. Use of modern antipsychotics is undergoing major increases for both BD and MDD; optimal use of antidepressants for BD remains uncertain; and notably, international use of lithium tended to increase in the present data.

Background: While bipolar disorder is strongly linked to an increased risk of suicide, recent evidence has challenged the assumption that mixed symptoms play a distinct role in suicidal ideation beyond depressive severity. This study examines how depressive, hypo/manic, and mixed features influence suicidal ideation in individuals with bipolar disorder. Data from 903 participants in the Stanley Foundation Bipolar Network (1995-2002) were analyzed to assess associations between mood states, classified by the Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C) and the Young Mania Rating Scale (YMRS), and suicidal ideation, measured using IDS-C item 18, using generalized estimating equations.

Results: Depressive symptoms were strongly associated with suicidal ideation (OR = 21.98, 95% CI: 15.31-31.54). Moderate hypo/manic symptoms also conferred risk (OR = 3.11, 95% CI: 1.51-6.49), and milder hypo/mania showed a weaker but significant association (OR = 1.74, 95% CI: 1.05-2.89). The highest suicidal ideation was observed in individuals with hypo/mania featuring mixed symptoms (OR = 29.43), exceeding that of depression or depression with mixed features (OR = 21.98). However, findings diverged based on modeling approach: in continuous predictor models, SI was driven solely by depressive symptom severity, with no significant association observed for hypo/mania or its interaction with depression. In contrast, when mood states were categorized using clinically meaningful thresholds, hypo/mania with mixed features emerged as a distinct contributor to suicidal ideation risk.

Conclusion: These findings underscore the need for integrating both dimensional and categorical approaches to mood state classification in research on suicidality in bipolar disorder.

Background: Despite evidence that psychological interventions improve recovery for bipolar disorder, access to these in the United Kingdom is limited; online delivery provides opportunities to increase this. Mood on Track is a psychological therapy programme for bipolar disorder combining a Cognitive Behavioural Therapy group intervention with individual relapse prevention. The present study reports on a feasibility and acceptability trial of Mood on Track online, implemented within a routine clinical service, in preparation for a Randomised Controlled Trial. The online version retains the therapeutic elements of the face-to-face intervention, but is delivered via Zoom over more sessions and includes online exercises and breakout rooms.

Method: A within-groups non-randomised longitudinal interventional study of feasibility and acceptability. Participants completed psychometric questionnaires at four time points from baseline to six months post-group intervention to evaluate change in recovery. Feasibility and acceptability of the intervention and a future study were assessed by measuring recruitment, intervention attendance and outcome measure completion.

Results: Rates of recruitment, intervention completion and outcome measure completion demonstrate that Mood on Track online and a larger future trial are feasible and acceptable. Analysis of efficacy found that the primary outcome measure of personal recovery on the Bipolar Recovery Questionnaire significantly increased between the start and end of the group intervention and continued to significantly increase at follow-up. Scores on the secondary outcome measure of the Generalised Anxiety Disorder-7 questionnaire decreased significantly between the start and end of the group intervention.

Conclusions: The present study provides quantitative evidence that a future RCT of Mood on Track online is feasible in terms of recruitment, delivery procedures and data collection. The findings provide promising evidence that Mood on Track online is an acceptable intervention to service users and shows signs of efficacy through significantly increased recovery and reduced anxiety. This adds to literature demonstrating that online psychological interventions are effective and provide an innovative method for delivery. Provision of digital therapies could increase offer and take-up of therapy for people with bipolar disorder and improve recovery.

Background: According to international guidelines, lithium treatment represents the gold standard for the appropriate management of persons with bipolar disorder. However, prescription rates in ordinary practice are not in line with clinical guidelines' suggestions. Clinicians prefer to use drugs other than lithium, considering its low therapeutic window, the need for regular lab tests and its side effects profile. Based on these premises, a Delphi-method study focused on highly-debated aspects of lithium treatment in bipolar disorder has been promoted with the aim to reach a consensus among an expert panel of Italian psychiatrists.

Methods: The Delphi method is a structured technique aimed to obtain a consensus from repeated rounds of questionnaires where opinion/agreement among experts are important. A Steering Committee of experts has developed a 24-items questionnaire exploring: (1) the use of lithium as first choice for treating different phases of bipolar disorder; (2) the side effect and tolerability profile of lithium treatment as hampering factors for its use in clinical practice; (3) the lithium prescribing in special target population, such as adolescents, elderly patients, and pregnant women.

Results: The questionnaire was delivered to a panel of 100 Italian psychiatrists, experts in the field of managing people with bipolar disorders. An almost complete positive consensus was reached for statements dealing with the use of lithium treatment as first choice in the management of patients with bipolar disorder, and as the first choice for preventing manic/hypomanic and depressive episodes.

Conclusions: Current clinical guidelines and scientific evidence support the use of lithium as first choice treatment in patients with bipolar disorder. However, over the last decades a downward tendency in lithium's prescription has been registered worldwide. The present Delphi study confirmed the "good clinical reasons" for supporting lithium prescription in clinical practice. Our findings should be used to develop clinical practice guidelines and reduce the discrepancy between international guidelines and ordinary care.

Background: The Swedish Bipolar Collection (SWEBIC) was launched to investigate the genetic basis of bipolar disorder. Here, we provide a detailed overview of the procedures and assessment tools used during the SWEBIC data collection.

Methods: The SWEBIC collection occurred in two waves, the first from 2009 to 2013, followed by the second wave from 2017 to 2022. Recruitment primarily relied on the Swedish National Quality Register for Bipolar Disorders (BipoläR). Additional sources included the Hospital Discharge Register, an online questionnaire, and identification of individuals with bipolar disorder from other cohort studies. We assessed the diagnostic validity of the BipoläR entries by reviewing randomly selected medical records from the study participants.

Results: Across the two waves, SWEBIC recruited 8580 individuals diagnosed with bipolar disorder, 89 percent from BipoläR. The bipolar disorder diagnoses in BipoläR showed high agreement with medical records (positive predictive value of 0.90). The response rate in BipoläR was higher during the first (61%) than the second wave (23%). Further, the proportion of individuals with subtype 1 was higher in the first wave. Including individuals from other cohort studies, the total number of DNA samples from individuals with bipolar disorder in SWEBIC exceeds 10,000.

Conclusions: Using quality registries to identify patients for large cohort studies facilitates genetic research with high recruitment efficiency and throughput combined with rich phenotypic data. The extensive data and biological samples collected in SWEBIC will continue to be a valuable resource for future studies, advancing our understanding of the genetic basis of bipolar disorder.

Background: The impacts of parental bipolar disorder (BD) on families and children highlight the need to understand how best to talk to children about their parents' diagnosis, especially as their developmental capacity for understanding grows. This qualitative study aims to explore the strategies, challenges, and support needs of parents in relation to communicating with their children (5-12 years) about BD, in order to inform the development of further interventions and resources.

Methodology: Purposive and snowball sampling strategies were used to recruit parents with BD, their partners, and stakeholders who support parents with BD. Recruitment occurred via social media, emails, and community outreach between April 2022 and April 2023. Semi-structured interviews were conducted with 11 parents with BD or non-BD partners and 12 charity workers or mental health professionals. The interview guides explored participants' lived experiences and professional insights into communicating about parental BD with children. Data were analysed using reflexive, inductive, thematic analysis.

Result: Participants identified several benefits of sharing parental BD diagnoses with children, including fostering understanding, adaptation, compassion, and strengthening family relationships. However, they also noted challenges such as uncertainty, stigma, and potential distress for children. To make communication effective, participants emphasised the importance of age-appropriate dialogue, addressing children's concerns, providing reassurance, and preparing them for future episodes. They highlighted that transparent, interactive communication, thoughtful timing, and collaboration with family members and professionals are crucial for tailoring the process to each family's unique needs.

Conclusion: Our findings underscore the complexities of communicating a parental BD diagnosis to children, highlighting both the potential benefits and challenges. Participants emphasised the need for developing interventions and policies specifically tailored to address the particular communication needs of families impacted by BD.

Background: The prevalence of substance use disorders in bipolar disorder (BD) is high. Exploring potential interactions between mood and the use of common substances such as alcohol and nicotine may contribute to a better understanding of the mechanisms underlying such comorbidities. Digital tools now allow for continuous monitoring and data collection of both symptoms and behavior. This enables time-series analyses to explore such associations with greater precision.

Methods: Thirty-two individuals in the early phases of BD registered their mood daily and their use of substances weekly in the MinDag (MyDay) app for up to 6 months. We explored temporal relationships between the use of alcohol and nicotine and the levels of depressed, elevated, irritable, and anxious mood using Vector Autoregressive Models and Granger causality tests.

Results: We found indications that mood influenced alcohol- and nicotine use, and vice versa. Significant temporal relationships (Granger causality) were found in 55% (11 out of 20) of the participants for alcohol and 70% (7 out of 10) for nicotine use, and with high proportions of the variance explained by the one time-series on the other. The associations were consistent with causal effects in one or both directions, but with no adjustment for confounding.

Conclusion: Our findings indicate that mood influences alcohol- and nicotine use and vice versa in individuals with BD, although caution should be taken due to the exploratory approach. Larger samples are needed to further disentangle these relationships to provide insight for better prevention and treatment of BD and comorbid substance use disorders.

This prospective observational study aimed to investigate the effects of Ramadan fasting on serum lithium levels, renal function, and electrolyte balance in patients with bipolar disorder undergoing lithium maintenance therapy. Conducted in Saudi Arabia, a region characterized by hot and arid climates (30-36 °C, 25% humidity during Ramadan 2024), the study included 250 participants divided into fasting (n = 131) and non-fasting (n = 119) groups. Serum lithium levels, renal function parameters (serum creatinine and estimated glomerular filtration rate), and electrolyte levels (sodium and potassium) were assessed at baseline, mid-Ramadan, one month post-Ramadan, and three months post-Ramadan. Statistical analyses included mixed-effects models, linear regression, and Wilcoxon rank-sum tests. The results indicate that Ramadan fasting did not significantly alter serum lithium levels, renal function, or electrolyte balance across all time points. These findings suggest that fasting during Ramadan can be safely practiced by patients with bipolar disorder receiving lithium therapy, provided they maintain adequate hydration and adhere to their prescribed medication regimen.

Background: Experimental studies consistently demonstrate that lithium modulates multiple intracellular signaling pathways involved in crucial neurobiological responses, highlighting its therapeutic potential in degenerative diseases. Lithium has demonstrated significant neuroprotective potential in preclinical models of Alzheimer's disease (AD) and other neurodegenerative disorders.

Contents: This review examines the molecular mechanisms and biological effects of lithium at subtherapeutic concentrations, focusing on its ability to modulate key intracellular pathways, such as the inhibition of glycogen synthase kinase-3 beta (GSK-3β), reduction of Tau hyperphosphorylation, and enhancement of neurotrophic and anti-inflammatory responses. Evidence from animal and cellular studies underscores lithium's ability to reduce amyloid plaques, maintain neuronal integrity, improve memory, and decrease neuroinflammation, even at doses much lower than those used clinically for mood stabilization.

Conclusion: Evidence from animal and cellular models indicates that subtherapeutic lithium doses may provide a safer and more practical approach to neuroprotection, particularly in AD. However, further research is necessary to optimize dosing strategies, assess long-term safety, and translate these findings into clinical applications.