International Journal of Bipolar Disorders最新文献

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.

Background: Despite significant research on bipolar disorder, the interplay between depression, suicide risk, and stigma in patients with bipolar disorder and their caregivers remains underexplored. This study aimed to examine how stigma and suicide risk affect the severity of depression in both patients with bipolar disorder and their caregivers.

Methods: We recruited 76 patients with bipolar disorder and their 76 caregivers from a general hospital between August 2023 and July 2024. Assessments included a psychiatric diagnostic interview using the Mini-International Neuropsychiatric Interview, the Hospital Anxiety and Depression Scale, the Family APGAR Index, the Stigma Subscale of the Explanatory Model Interview Catalogue, and the Suicide Assessment Scale. Structural equation modeling (SEM) was employed to explore the mechanisms underlying depression in caregivers. Additionally, a stepwise forward logistic regression model identified key factors associated with depressive disorders in caregivers.

Results: Among caregivers, depressive disorders were the most common psychiatric diagnosis (27.6%), followed by anxiety disorders (17.1%) and insomnia disorders (11.8%). SEM analysis revealed that suicidal ideation in patients (β = 0.72, p < 0.001) was significantly associated with depression severity in patients with bipolar disorder. Caregivers' stigma (β = 0.41, p < 0.001) and suicide risk (β = 0.39, p < 0.001) were positively associated with their own depression severity. Interestingly, caregivers' suicide risk (β = -0.20, p < 0.01) was inversely related to patients' depression severity. Unemployment, anxiety severity, suicide risk, and family support were also significant predictors of depression in caregivers.

Conclusions: Suicidal ideation in patients with bipolar disorder is strongly linked to the severity of their depressive symptoms. Among caregivers, higher levels of stigma and suicide risk are associated with greater depressive symptom severity, while caregivers' suicide risk appears to have a protective effect on patients' depression severity. Early identification and targeted interventions for individuals at high risk of suicide and stigma may help alleviate depression in both patients and their caregivers.

Background: The app "MinDag" (MyDay) was developed as a tool for monitoring mood, symptoms and illness-relevant behaviour in the initial treatment of bipolar disorder. Digital self-monitoring may provide patients and clinicians with valuable data for tailoring treatment interventions. This study aims to evaluate the practical use and clinical implications of integrating MinDag in the early treatment of bipolar disorder from the perspectives of both patients and clinicians.

Methods: The MinDag app includes six content modules covering mood, sleep, functioning/activities, substance use, emotional reactivity, and psychotic symptoms. Patients were asked to use the app for six months, and automated feedback based on the app registrations was delivered to the patients' clinicians biweekly. The study involved quantitative evaluations completed by patients (n = 20), as well as interviews with patients (n = 7) and clinicians (n = 2).

Results: Overall, the patients reported that they felt that MinDag was safe, relevant and easy to use, although technical difficulties such as too many automated reminders and need for reinstallations were reported. The patients appreciated the potential for increased awareness of their mental health, but expressed a desire for direct access to their data. Clinicians found the visual reports and feedback useful for tailoring treatment, even though the alert system for high-risk variables needed refinement. The quantitative evaluations indicated a positive general reception, with suggestions for improvement in usability and accessibility.

Conclusion: The MinDag app shows promise as a tool for enhancing the treatment of bipolar disorder by facilitating self-monitoring and providing actionable data to clinicians. However, technical issues and the need for direct patient access to data must be addressed. Development of digital tools to support the treatment of bipolar disorder and other mental health conditions is resource demanding, and there is a need to clarify criteria to establish proof of concept to guide the selection of tools for upscaling and implementation.

Anticipating clinical transitions in bipolar disorder (BD) is essential for the development of clinically actionable predictions. Our aim was to determine what is the earliest indicator of the onset of depressive symptoms in BD. We hypothesized that changes in activity would be the earliest indicator of future depressive symptoms. The study was a prospective, observational, contactless study. Participants were 127 outpatients with a primary diagnosis of BD, followed up for 12.6 (5.7) [(mean (SD)] months. They wore a smart ring continuously, which monitored their daily activity and sleep parameters. Participants were also asked to complete weekly self-ratings using the Patient Health Questionnaire (PHQ-9) and Altman Self-Rating Mania Scale (ASRS) scales. Primary outcome measures were depressive symptom onset detection metrics (i.e., accuracy, sensitivity, and specificity); and detection delay (in days), compared between self-rating scales and wearable data. Depressive symptoms were labeled as two or more consecutive weeks of total PHQ-9 > 10, and data-driven symptom onsets were detected using time-frequency spectral derivative spike detection (TF-SD²). Our results showed that day-to-day variability in the number of steps anticipated the onset of depressive symptoms 7.0 (9.0) (median (IQR)) days before they occurred, significantly earlier than the early prediction window provided by deep sleep duration (median (IQR), 4.0 (5.0) days; p <.05). Taken together, our results demonstrate that changes in activity were the earliest indicator of depressive symptoms in participants with BD. Transition to dynamic representations of behavioral phenomena in psychiatry may facilitate episode forecasting and individualized preventive interventions.

Background: Employment is a challenging life domain for individuals with bipolar disorder (BD), illustrated by high unemployment numbers and various experienced problems within the workplace. While regaining a satisfactory level of occupational functioning is an important aspect of recovery, there is little qualitative research exploring occupational recovery in individuals with BD. The aim of this qualitative study was first to gain insight into the (self-regulation) strategies used by patients and peer support workers with BD type I (BD-I) regarding their occupational functioning. Our second aim was to construct a conceptual model based on these strategies used to better understand how individuals with BD-I might recover during their occupational functioning. In our study, inspired by Glaser and Strauss' constructivist Grounded Theory, we interviewed 21 patients and 15 peer support workers with BD-I about their experiences in occupational functioning and about the strategies they use for dealing with difficulties, as well as their occupational recovery processes. We analysed the data through open, axial, and selective coding.

Results: The results showed one overarching theme and three subthemes of strategies used by individuals with BD-I: (1) organizing work, (2) self-regulatory actions in relation to employment, and (3) getting support. Based on the narratives of the participants, a conceptual model was found in which differing strategies are used based on the recovery process: acute mood episode or longer lasting recovery process.

Conclusion: The narratives of individuals with BD-I show that two types of recovery can be experienced in relation to work: recovery after an acute mood episode and a longer lasting recovery process that is intertwined with several aspects of daily working life. We identified three different types of strategies that participants with BD-I implement to create a fitting employment situation and that it might depend on the type of recovery process which strategies are most helpful.

Bipolar depression is commonly accompanied by cognitive impairments. Transcranial direct current stimulation (tDCS) is emerging as a novel non-invasive treatment for bipolar depression. Given the portability and safety of tDCS, we developed a home-based protocol with real-time supervision. Our aim was to assess the cognitive effects of a course of tDCS treatment in bipolar depression. 44 participants (31 women, mean age 47.27 years, SD 12.89) with bipolar depression of at least a moderate severity received 21 sessions of home-based tDCS over 6 weeks in an open-label design. The stimulation protocol involved 2 mA in a bilateral frontal montage (F3 anode, F4 cathode) for 30 min per session. Cognitive assessments were conducted at baseline and after the course of treatment: Rey Auditory Verbal Learning Test (RAVLT) to assess verbal learning and memory and Symbol Digit Modalities Test (SDMT) to assess psychomotor processing speed and visuospatial attention. 93.18% (n = 41) completed RAVLT and 59.09% of participants (n = 26) completed SDMT. A significant improvement was observed in RAVLT verbal learning score post-treatment (p = 0.002), which was not maintained following adjustment for improvement in depressive symptoms. In summary, a course of home-based tDCS in bipolar depression was associated with an improvement in verbal learning, which appeared to be related to improvement in depressive symptoms. These findings suggest potential benefits of tDCS for addressing cognitive impairments in bipolar depression, which can be investigated further in a sham-controlled design.

Background: Oxidative stress may be involved in the pathophysiology of bipolar disorder (BD). Malondialdehyde (MDA), a product of fatty acid peroxidation has been proposed as a trait marker of BD associated with familial risk. However, little is known about MDA levels in young patients newly diagnosed with BD and their unaffected first-degree relatives (UR).

Methods: In this substudy of the ongoing longitudinal "Bipolar Illness Onset study", we included baseline data and first, we compared fasting blood MDA levels in 130 young patients aged 15-25 years newly diagnosed with BD, 57 UR, and 88 healthy control individuals (HC). Second, we investigated associations between levels of MDA and illness variables in patients with BD. Third, we investigated associations between MDA levels and nucleoside damage by oxidation measured in urine. Fasting MDA levels from blood samples were measured using high-performance liquid chromatography (HPLC).

Results: In linear mixed effect models, adjusted for age and sex, MDA levels did not differ between patients with BD, UR, and HC, respectively. In patients with BD, we found no associations between levels of MDA and duration of illness, number of affective phases, illness onset or oxidatively damaged RNA and DNA.

Conclusion: Against expectations, MDA levels did not differ between young patients with BD, UR, and HC, thus, our findings did not support MDA being a state or a trait marker of BD associated with familial risk.

Background: The postpartum period is associated with a high risk of illness episodes in women with bipolar disorder (BD) and is a critical developmental phase for both a new mother and her infant. This mixed-methods study aimed to investigate the occurrence of mood symptoms among infant mothers with BD in the first year postpartum, as well as their perceptions of the first year, their challenges and their strategies for wellbeing.

Methods: Twenty-six women with BD participated. Mood symptoms were assessed at 3 and 12 months postpartum with the Inventory of Depressive Symptomatology and Young Mania Rating Scale. Occurrences of additional postpartum mood deviations were investigated through an interview at 12 months, which also covered the women's postpartum experiences. Thematic analysis was applied to the qualitative dataset (interviews and field notes).

Results: 42% of the women were euthymic or had only mild mood symptoms at 3 and 12 months. 58% had moderate to severe symptoms at either or both time points. A positive (38%) vs. mixed (62%) perception of the first year was strongly associated with euthymia-mild vs. moderate-severe mood deviations, as was the experience of maternal developmental achievement vs. struggles. The women experienced postpartum mood deviations and illness episodes as being particularly poorly timed. Further challenges included balancing self-care and infant mothering, familial relations, and negative experiences with the health and care systems. Illness acceptance with mindfulness of one's own and the infant's needs was a primary strategy for wellbeing, which was complemented by the support of one's partner and family and postpartum treatment.

Conclusions: Our findings propose that without impeding mood deviations and concomitant challenges, infant mothers with BD can enjoy their new motherhood and experience phase-specific growth equally to healthy mothers. On the other hand, moderate to severe mood deviations can adversely impact the experience of the postpartum year and one's own sense of mothering. Efforts to prevent postpartum mood deviations need to be complemented with interventions that target phase-specific BD challenges and support wellbeing strategies for both the mother and her infant. In summary, women's needs to function as infant mothers must be considered in the postpartum treatment of BD.

Background: Little is known about the effect of ethnicity on drug treatment in patients with an acute manic episode. The aim of this study is to determine whether ethnicity moderates the response to drug treatment in patients with an acute manic episode, and whether this moderation is independent of potential confounders.

Methods: We analysed ten short-term placebo-controlled registration trials of atypical antipsychotics and anticonvulsive mood stabilizers in patients with an acute manic episode (n = 2199). A one-step random effects individual patient data meta-analysis (IPD) was applied to establish the moderating effect of ethnicity on symptom improvement on the Young Mania Rating Scale (Y)MRS and on response defined as 50% (Y)MRS symptom reduction. These analyses were corrected for baseline severity, age, and gender. A two-step IPD comparing these outcomes between White, Black and Asian patients. Additionally, a conventional meta-analysis was performed to determine the effect size of drug treatment separately for these ethnic groups.

Results: In the complete dataset, 60.4% of the patients was White, 8.0% was Black, 12.7% was Asian, 33.7% was of other ethnicities. Ethnicity did not significantly moderate the efficacy of drug treatment: pooled beta-coefficient (β) for the interaction between treatment and the ethnicities White, Black and Asian, varying from 0.889 to 0.899 with overlapping confidence-intervals ranging from 2.356 to 2.430 in the main analysis. The drug treatment effects were significant in all three analysable ethnicity groups compared to placebo.

Discussion: In White,Black, and Asian patients with an acute manic episode drug treatment is equally effective.

Background: Improving quality of life (QoL) is important for the treatment of people with bipolar disorder (BD). Early-BipoLife is a German multicentre naturalistic, prospective-longitudinal observational cohort study investigating early recognition and intervention in people at increased risk of developing a BD. This analysis aims to investigate influencing factors and changes in QoL as a basis for the development of early intervention strategies in patients with at risk syndrome for BD.

Method: A cohort of 1086 participants (15-35 years) with at least one risk factor (EPIbipolar criteria) for BD was assessed over the course of 2 years. Changes in QoL (WHOQOL-BREF) were evaluated in a mixed model for repeated measures.

Results: Compared to an age-matched comparison group, people at risk for BD showed significant lower QoL in all domains at baseline. The overall QoL of the psychological well-being domain of the WHOQOL-BREF increased over the 2 year study course (p < 0.001). The bipolar risk group (EPIbipolar) change from baseline divided into (a) decreasing, (b) increasing and (c) constant risk group in the course of 2 years. Baseline risk group assignment was not a significant predictor of change in QoL over 2 years for any of the QoL domains, but participants with an increase in risk over the 2-year course had a significantly smaller gain in QoL than the group with constant risk (p = 0.014) or decreasing risk (p < 0.001). Higher levels of QoL were associated with a higher self-rated ability to use coping strategies. Moreover, a higher level of functioning (GAF) at baseline was positively correlated with improvement of different QoL domains after 2 years.

Conclusion: Patients with a risk syndrome for BD reported significantly reduced QoL compared to their age-matched comparison group. Risk status monitoring might be beneficial to identify individuals who could profit from an intervention to increase their QoL. Further studies promoting the development of coping strategies for successful self-management could be helpful to improve overall mental health and positively influence QoL.