International Journal of Bipolar Disorders最新文献

Background: Diagnosing bipolar disorder (BD) is challenging, and adequate treatment is of major importance to minimalize the consequences of the illness. Early recognition is one way to address this. Although in clinical research the prodromal phase of BD is gaining interest, the perspective of patients with BD and their caregivers on prodromal symptoms is still lacking. The aim of this study is to gain insights in prodromal symptoms of patients with BD and their caregivers before the onset of a first manic episode.

Methods: A qualitative research method was used to investigate prodromal symptoms one year prior to a first manic episode. In-depth interviews were conducted with patients with BD type I and their caregivers. Only patients with a first manic episode in the previous five years were included.

Results: The prodromal symptoms from patients' and caregivers' perspectives could be clustered into seven themes, with underlying subthemes: behavior (increased activity, destructive behavior, disinhibited behavior, inadequate behavior, changes in appearance), physical changes (changes in sleep, physical signals, differences in facial expression), communication (reciprocity, process, changes in use of social media), thought (process and content), cognition (changes in attention and concentration, forgetfulness), emotions (positive emotions, more intense emotions, mood swings), and personality (more pronounced manifestation of existing personality traits).

Conclusion: Patients with bipolar I disorder and their caregivers described subsyndromal manic features one year prior to a first manic episode. In addition, they recognized mood lability, physical changes and more pronounced manifestation of existing personality traits. The results of this study confirm the presence of a prodromal phase. In clinical practice, monitoring of prodromal symptoms of BD can be useful in patients with depression, especially those with a familial risk of BD.

Background: Increased awareness of the factors contributing to the diagnostic disparities seen in bipolar disorder between individuals of different heritage is needed to achieve equity in diagnosis and treatment. One such inequity is the provision of earlier treatment. Earlier treatment of patients diagnosed with bipolar disorder may prolong time to recurrence of mood episodes and reduce functional impairment and other poor outcomes associated with disease progression. The aim of this post hoc analysis was to study the efficacy and safety of long-acting injectable aripiprazole once-monthly 400 mg (AOM 400) in patients with earlier-stage bipolar I disorder (BP-I). Data from a 52-week multicenter, double-blind, placebo-controlled, randomized withdrawal trial of AOM 400 versus placebo in patients with BP‑I (NCT01567527) were analyzed. Those patients in the lowest quartiles for age (18-≤32 years; n = 70) or disease duration (0.13-≤4.6 years; n = 67) at baseline were categorized with earlier-stage BP-I. The primary endpoint was time from randomization to recurrence of any mood episode. Other endpoints included proportion of patients with recurrence of any mood episode, and change from baseline in Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores.

Results: Maintenance treatment with AOM 400 significantly delayed time to recurrence of any mood episode versus placebo in patients aged 18-≤32 years (hazard ratio [HR]: 2.46 [95% confidence interval (CI) 1.09, 5.55]; p = 0.0251) or with disease duration 0.13-≤4.6 years (HR: 3.21 [95% CI 1.35, 7.65]; p = 0.005). This was largely driven by a lower proportion of patients in the AOM 400 group with YMRS total score ≥15 or clinical worsening. Changes from baseline in MADRS total score in both earlier-stage groups indicated AOM 400 did not worsen depression versus placebo. The safety profile of AOM 400 was consistent with the original study. Note that the original study included patients who had previously been stabilized on AOM 400 monotherapy, which may have enriched the population with patients who respond to and tolerate AOM 400.

Conclusions: In this post hoc analysis, AOM 400 prolonged time to recurrence of any mood episode versus placebo in earlier-stage BP-I. These findings support early initiation of maintenance treatment with AOM 400.

Background: Despite a variability in response and a narrow therapeutic index, Lithium (Li) remains the gold standard treatment for bipolar disorders (BD), and a treatment of choice for unipolar disorders (UD). Red blood cell Li concentration (RBCLiC) and red blood cell/plasma Li ratio (LiR) have been studied in many areas of mood disorders (such as acute or chronic Li efficacy, adherence, side effects (SE), intoxication management) as well as in several research domains. This systematic review aims to synthesize the existing literature.

Methods: We conducted a systematic review, based on preferred reporting items for systematic reviews and Metanalysis (PRISMA) guidelines, of articles published between 1972 and February 2023, indexed in the following databases: EMBASE, MEDLINE, Cochrane Library. The search terms were combinations of the following headings: "Lithium AND Plasma AND Erythrocyte AND Mood disorders". The systematic review protocol was published to PROSPERO (CRD42023406154).

Results and conclusion: Out of the 252 identified studies, 57 met the selection criteria. The articles investigated the interest of RBCLiC and other blood parameters (PLiC and LiR) in various areas: (i) disease management (31 articles) (compliance/adherence (5 articles), SE/toxicity (13 articles), prediction of Li response/therapeutic efficacy for acute episode or for relapse prevention (17 articles)), (ii) Li blood parameters as trait markers of mood disorders subtypes (UD, BDI, BDII) (16 articles), (iii) Li blood parameters as state markers of mood episodes (11 articles), (iv) factors influencing Li blood parameters (age, gender, ethnicity, dosage and duration of Li treatment, co-medications with other treatments, seasonality) associated with RBCLiC or LiR (24 articles), and (v) potential pathophysiological mechanisms (30 articles).

Conclusion: Overall, this review suggests that RBCLiC or LiR could be of interest for tolerance monitoring. However, the heterogeneity of methods and results, coupled with the limited amount of data, does not allow clear conclusions to be drawn in the other areas explored in this literature review. Given the potential interest in exploring brain Li pharmacokinetics (PK)s, this review calls for further research.

Background: Adults with bipolar disorder (BD) commonly present with cognitive deficits. Many also report subjective or perceived cognitive failures. For this study, we identified four distinct clusters of adults with BD on the basis of both BD symptoms (depression and hypo/mania) and perceived cognitive errors (i.e., forgetfulness, distractibility, false triggering). We hypothesized that participants reporting more BD symptoms and cognitive errors would report lower psychological well-being (i.e., self-efficacy, life scheme, life satisfaction). A second objective was to determine if and how clusters differed in terms of BD related factors (e.g., subtypes, sleep, medications) and sociodemographic differences such as age of participants. From the BADAS (Bipolar Affective Disorder and older Adults) Study, we identified 281adults with BD (M = 44.27 years of age, range 19-81), recruited via social media.

Results: All clusters significantly differed across all grouping variables except symptoms of hypo/mania due to low frequency. Across clusters, perceived cognitive failures and BD symptoms increased in lockstep; that is, those reporting more cognitive errors also reported significantly higher symptoms of both depression and hypo/mania. As hypothesized, they also reported significantly lower psychological well-being.

Conclusions: Age did not significantly differ across clusters in contrast to existing research in which cognitive loss is objectively measured. That is, perceived cognitive errors are significantly associated with lower psychological well-being for both young and older adults with BD.

Background: The German multicenter research consortium BipoLife aims to investigate the mechanisms underlying bipolar disorders. It focuses in particular on people at high risk of developing the disorder and young patients in the early stages of the disease. Functional and structural magnetic resonance imaging (MRI) data was collected in all participating centers. The collection of neuroimaging data in a longitudinal, multicenter study requires the implementation of a comprehensive quality assurance (QA) protocol. Here, we outline this protocol and illustrate its application within the BipoLife consortium.

Methods: The QA protocol consisted of (1) a training of participating research staff, (2) regular phantom measurements to evaluate the MR scanner performance and its temporal stability across the course of the study, and (3) the assessment of the quality of human MRI data by evaluating a variety of image metrics (e.g., signal-to-noise ratio, ghosting level). In this article, we will provide an overview on these QA procedures and show exemplarily the influence of its application on the results of standard neuroimaging analysis pipelines.

Discussion: The QA protocol helped to characterize the various MR scanners, to record their performance over the course of the study and to detect possible malfunctions at an early stage. It also assessed the quality of the human MRI data systematically to characterize its influence on various analyses. Furthermore, by setting up and publishing this protocol, we define standards that must be considered when analyzing data from the BipoLife consortium. It further promotes a systematic evaluation of data quality and a definition of subject inclusion criteria. In the long term, it will help to increase the chance of achieving clinically relevant results.

Background: Since its debut in 1949, lithium (Li) has been regarded as a gold standard therapy for mood stabilization. Neuroprotective effects of Li  have been replicated across many different paradigms ranging from tissue cultures to human studies. This has generated interest in potentially repurposing this drug. However, the optimal dosage required for neuroprotective effects remains unclear and may be different than the  doses needed for treatment of bipolar disorders. Recent studies on trace-Li levels in the water suggest that Li, could slow cognitive decline and prevent dementia with long-term use even at very low doses. The current review aims to synthesize the data on the topic and challenge the conventional high-dose paradigm.

Results: We systematically reviewed five available studies, which reported associations between trace-Li in water and incidence or mortality from dementia. Association between trace-Li levels and a lower risk or mortality from dementia were observed at concentrations of Li in drinking water as low as 0.002 mg/L and 0.056 mg/L. Meanwhile, levels below 0.002 mg/L did not elicit this effect. Although three of the five studies found dementia protective properties of Li in both sexes, a single study including lower Li levels (0.002 mg/l) found such association only in women.  CONCLUSION: The reviewed evidence shows that trace-Li levels in the water are sufficient to lower the incidence or mortality from dementia. Considering the lack of options for the prevention or treatment of dementia, we should not ignore these findings. Future trials of Li should focus on long term use of low or even micro doses of Li in the prevention or treatment of dementia.

Background: Alongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder.

Methods: A total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ.

Results: In seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=-0.539, p = 0.005), long delay free recall (r=-0.423, p = 0.035), and immediate recall sum trial 1-5 (r=-0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed.

Conclusions: This investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships.

Background: Current treatments for bipolar depression have limited effectiveness, tolerability and acceptability. Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation method that has demonstrated treatment efficacy for major depressive episodes. tDCS is portable, safe, and individuals like having sessions at home. We developed a home-based protocol with real-time remote supervision. In the present study, we have examined the clinical outcomes, acceptability and feasibility of home-based tDCS treatment in bipolar depression.

Results: Participants were 44 individuals with bipolar disorder (31 women), mean age 47.27 ± 12.89 years, in current depressive episode of at least moderate severity (mean Montgomery Asberg Depression Rating Scale (MADRS) score 24.59 ± 2.64). tDCS was provided in bilateral frontal montage, F3 anode, F4 cathode, 2 mA, for 30 min, in a 6-week trial, for total 21 sessions, a follow up visit was conducted 5 months from baseline. Participants maintained their current treatment (psychotherapy, antidepressant or mood stabilising medication) or maintained being medication-free. A research team member was present by video conference at each session. 93.2% participants (n = 41) completed the 6-week treatment and 72.7% of participants (n = 32) completed the 5 month follow up. There was a significant improvement in depressive symptoms following treatment (mean MADRS 8.77 ± 5.37) which was maintained at the 5 month follow up (mean MADRS 10.86 ± 6.90), rate of clinical response was 77.3% (MADRS improvement of 50% or greater from baseline), and rate of clinical remission was 47.7% (MADRS rating of 9 or less). Acceptability was endorsed as "very acceptable" or "quite acceptable" by all participants. No participants developed mania or hypomania.

Conclusions: In summary, home-based tDCS with real-time supervision was associated with significant clinical improvements and high acceptability in bipolar depression. Due to the open-label design, efficacy findings are preliminary.

Trial registration: ClinicalTrials.gov number NCT05436613 registered on 23 June 2022 https//www.

Clinicaltrials: gov/study/NCT05436613.