International Journal of Bipolar Disorders最新文献

Background: Response to lithium (Li) is highly variable in bipolar disorders (BD). Despite decades of research, no clinical predictor(s) of response to Li prophylaxis have been consistently identified. Recently, we developed epigenetic Methylation Specific High-Resolution Melting (MS-HRM) assays able to discriminate good responders (GR) from non-responders (NR) to Li in individuals with BD type 1 (BD-I). This study examined whether a combination of clinical and epigenetic markers can distinguish NR from other types of Li responders.

Methods: We recorded clinical variables that are potentially associated with Li response in 64 individuals with BD-I. MS-HRM assays were performed on DNA isolated from peripheral blood. We used backward stepwise logistic regression analyses, followed by receiver operating characteristic (ROC) curve analysis to estimate the performance of the clinical variables, alone then in combination with the epigenetic biomarkers, to identify GR and partial responders (PaR) vs NR.

Results: Polarity at onset, psychotic symptoms at onset and family history of BD classified correctly 70% of individuals according to their Li response (PaR + GR = 86%; NR = 35%). When combined with the epigenetic biomarkers, these three clinical variables plus alcohol misuse (and one DMR: Differentially Methylated Region) correctly classified 86% of individuals, improving the prediction of PaR + GR (93%) and of NR (70%). The ROC analysis demonstrated an improvement in the area under the curve from 0.75 (clinical variables alone) to 0.87 (combination of clinical and epigenetic markers).

Conclusions: Combining clinical predictors and DNA methylation markers of Li response may have greater utility in clinical practice than relying on clinical characteristics alone.

Background: Physical exercise (PE) is a recommended lifestyle intervention for different mental disorders and has shown specific positive therapeutic effects in unipolar depressive disorder. Considering the similar symptomatology of the depressive phase in patients with bipolar disorder (BD) and unipolar depressive disorder, it is reasonable to suggest that PE may also be beneficial for bipolar depression. However, there is an absence of studies evaluating the antidepressant effect of a structured PE intervention in BD.

Methods: This is an open-label, single-arm study trial. Fifteen patients with a diagnosis of BD Type I or Type II, presenting a depressive episode were included in the study. After physical and functional evaluation, patients participated in supervised training sessions with aerobics followed by strength exercises, three times per week, for 12 weeks (36 training sessions). Depressive and manic symptoms were assessed at baseline and 2, 4, 8, and 12 weeks. Additionally, quality of Life and functioning were assessed at baseline and 4, 8, and 12 weeks). Finally, we tested cardiorespiratory fitness, muscle strength and body composition at baseline and week-12.

Results: The mean (± SD) Montgomery Asberg Depression Rating Scale (MADRS) score at baseline was 23.6 ± 8.3 points and after 12 weeks of PE the mean score was 10.2 ± 4.8 points. Nine patients (82%) presented an antidepressant response defined as a reduction of more than 50% of depressive symptoms at week 12 with five of those patients (45%) presenting criteria for full remission. A large and significant Cohen's D Effect Size (pre-post) was verified for MADRS reduction [1.98 (95% Confidence interval = 0.88 to 3.08)]. We did not detect a significant change in manic symptoms, functioning, and quality of life during the 12-week follow-up. At week-12, all patients increased their muscular strength (one repetition maximal test - 1RM) and reduced the percentage of body fat (spectral bioelectrical impedance analysis).

Conclusions: This study, using rigorous criteria and a structured intervention, provides valid pilot data, showing the feasibility of a structured PE intervention for the treatment of depressive symptoms in BD, and suggesting a potential adjunctive antidepressant effect. Moreover, PE showed a positive impact on muscle strength and body composition. This should be further verified by randomized controlled studies.

Background: When assessing the value of an intervention in bipolar disorder, researchers and clinicians often focus on metrics that quantify improvements to core diagnostic symptoms (e.g., mania). Providers often overlook or misunderstand the impact of treatment on life quality and function. We wanted to better characterize the shared experiences and obstacles of bipolar disorder within the United States from the patient's perspective.

Methods: We recruited 24 individuals diagnosed with bipolar disorder and six caretakers supporting someone with the condition. Participants were involved in treatment or support services for bipolar disorder in central Texas. As part of this qualitative study, participants discussed their everyday successes and obstacles related to living with bipolar disorder during personalized, open-ended interviews. Audio files were transcribed, and Nvivo software processed an initial thematic analysis. We then categorized themes into bipolar disorder-related obstacles that limit the patient's capability (i.e., function), comfort (i.e., relief from suffering) and calm (i.e., life disruption) (Liu et al., FebClin Orthop 475:315-317, 2017; Teisberg et al., MayAcad Med 95:682-685, 2020). We then discuss themes and suggest practical strategies that might improve the value of care for patients and their families.

Results: Issues regarding capability included the struggle to maintain identity, disruptions to meaningful employment, relationship loss and the unpredictable nature of bipolar disorder. Comfort related themes included the personal perception of diagnosis, social stigma and medication issues. Calm themes included managing dismissive doctors, finding the right psychotherapist and navigating financial burdens.

Conclusions: Qualitative data from patients with bipolar disorder helps identify gaps in care or practical limitations to treatment. When we listen to these individuals, it is clear that treatments must also address the unmet psychosocial impacts of the condition to improve patient care, capability and calm.

Background: Bipolar disorder type-I (BD-I) patients are known to show emotion regulation abnormalities. In a previous fMRI study using an explicit emotion regulation paradigm, we compared responses from 19 BD-I patients and 17 matched healthy controls (HC). A standard general linear model-based univariate analysis revealed that BD patients showed increased activations in inferior frontal gyrus when instructed to decrease their emotional response as elicited by neutral images. We implemented multivariate pattern recognition analyses on the same data to examine if we could classify conditions within-group as well as HC versus BD.

Methods: We reanalyzed explicit emotion regulation data using a multivariate pattern recognition approach, as implemented in PRONTO software. The original experimental paradigm consisted of a full 2 × 2 factorial design, with valence (Negative/Neutral) and instruction (Look/Decrease) as within subject factors.

Results: The multivariate models were able to accurately classify different task conditions when HC and BD were analyzed separately (63.24%-75.00%, p = 0.001-0.012). In addition, the models were able to correctly classify HC versus BD with significant accuracy in conditions where subjects were instructed to downregulate their felt emotion (59.60%-60.84%, p = 0.014-0.018). The results for HC versus BD classification demonstrated contributions from the salience network, several occipital and frontal regions, inferior parietal lobes, as well as other cortical regions, to achieve above-chance classifications.

Conclusions: Our multivariate analysis successfully reproduced some of the main results obtained in the previous univariate analysis, confirming that these findings are not dependent on the analysis approach. In particular, both types of analyses suggest that there is a significant difference of neural patterns between conditions within each subject group. The multivariate approach also revealed that reappraisal conditions provide the most informative activity for differentiating HC versus BD, irrespective of emotional valence (negative or neutral). The current results illustrate the importance of investigating the cognitive control of emotion in BD. We also propose a set of candidate regions for further study of emotional control in BD.

Background: Patients should get actively involved in the management of their illness. The aim of this study was to assess the influence of lifestyle factors, including sleep, diet, and physical activity, on lithium levels in patients with bipolar disorder.

Methods: A multicenter study was performed. In total, 157 lithium measurements were done biweekly in a sample of 65 patients (35 women) over 6 weeks. Lifestyle, based on total sleep hours and physical activity, was assessed by actigraphy. Diet was evaluated using the Mediterranean Lifestyle Index (Medlife).

Results: 35.4% of patients had a normal weight. The mean Medlife score was 14.5 (± 2.5) (moderate-good adherence to Mediterranean diet). BMI, daily dose of lithium and intensity of physical activity had a combined effect on lithium levels, after adjustment for other variables. Patients who practiced intense physical exercise, who took lower doses and had a higher BMI exhibited lower levels of lithium.

Conclusions: Higher physical activity and BMI contribute to lower lithium levels. Patients should be made aware of these relationships to improve their perception of control and self-management. Lifestyle-based interventions contribute to establishing a more personalized medicine.

Background: Offspring of parents with bipolar disorder (OBD) are at risk for developing mental disorders, and the literature suggests that parenting stress may represent an important risk factor linking parental psychopathology to offspring psychopathology. We aimed to investigate whether improvements in parenting stress mediated the relationship between participation in a prevention program and offspring internalizing and externalizing symptoms at follow-up.

Methods: Families having a parent with BD (N = 25) underwent a 12-week prevention program. Assessments were conducted at pre-intervention, post-intervention, and at 3- and 6-month follow-ups. Families of parents with no affective disorders (i.e., control families) served as a comparison sample (N = 28). The Reducing Unwanted Stress in the Home (RUSH) program aimed to teach communication, problem-solving, and organization skills to improve the rearing environment. Measures included the Parenting Stress Index-4th Edition, the Behaviour Assessment Scales for Children-2nd Edition, and the UCLA Life Stress Interview.

Results: Families having a parent with BD reported more parenting stress at pre-intervention, and more change across time, than control families. Improvements in parenting stress mediated the relationship between participation in the intervention and reduced offspring internalizing and externalizing symptoms. While families having a parent with BD reported more chronic interpersonal stress at pre-intervention, no intervention effects were found.

Conclusions: The findings demonstrate that a preventative intervention targeting parenting stress in families may serve to prevent the development of mental disorders in at-risk children.

Background: Stigma affects different life aspects in people living with bipolar disorder and their families. This study aimed to examining the experience of stigma and evaluating predictors, consequences and strategies to combat stigma in people with bipolar disorder and their families.

Methods: We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) in 2022. We extensively reviewed six online databases (PubMed, Scopus, Medline, EMBASE, Web of Science and Google Scholar). Articles published in the English language about stigma in people living with bipolar disorders and their families were included.

Results: A total of 42,763 articles were retrieved, of which 40 articles from 14 countries were included in this study (n = 7417 participants). Of the 40 articles, 29 adopted quantitative methods (72.5%), two used mixed-methods (5%), eight used qualitative (20%) methods, and one was a case series (2.5%). The results of the studies were categorized into four themes: 1. Stigma experienced by people living with bipolar disorders and their families, 2. Predictors of stigma in people living with bipolar disorders and their families, 3. Consequences of stigma in people living with bipolar disorders and their families, 4. Effective interventions and strategies to reduce stigma in people living with bipolar disorders and their families.

Conclusion: The results of this study might be useful to design psychiatric cognitive interventions to reduce stigma in people living with bipolar disorders and their families and designing community-based interventions to normalize bipolar disorder at the community level.

Background: Lithium is one of the most consistently effective treatment for mood disorders. However, patients may show a high level of heterogeneity in treatment response across the lifespan. In particular, the benefits of lithium use may vary in special clinical conditions. The aim of this study was to test this hypothesis by conducting an umbrella review on the efficacy and safety of lithium in childhood and adolescence, peripartum and old age.

Methods: We applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA) to identify systematic reviews/meta-analyses on the efficacy and/or safety of lithium in mood disorders in special clinical conditions: (i) childhood and adolescence; (ii) peripartum (pregnancy, postpartum and lactation); (iii) old age. The Risk of Bias Assessment Tool for Systematic Reviews (ROBIS) tool was used to assess the risk of bias. Overlap in primary studies across systematic reviews was calculated through the Corrected Covered Area (CCA).

Results: We included 20 independent studies, for a total of 8209 individuals treated with lithium. Regarding paediatric age, efficacy and safety results suggested that lithium may be superior to placebo in bipolar disorders (BD) and not associated with serious adverse events. Nevertheless, primary available data are very limited. Efficacy in paediatric major depressive disorder (MDD) is not clear. During peripartum, lithium use was superior to non-lithium in preventing mood episodes and it was associated with low risk of congenital anomalies and with normal child neurodevelopment. Regarding old age, limited evidence supported lithium as an effective treatment in BD and resistant MDD; low doses should be used in this population. Systematic reviews on paediatric age showed the lowest risk of bias (80% of the studies at low risk). The CCA range of included studies was 13-47%.

Conclusions: This umbrella review supports the use of lithium across the lifespan, including special clinical condition. Nevertheless, more studies with increased methodological homogeneity are needed.

Background: Bipolar disorder (BD) is higher in developing countries. Childhood trauma exposure is a common environmental risk factor in Colombia and might be associated with a more severe course of bipolar disorder in Low-Middle Income-Countries. We carried out the first case-control study in Colombia using a structural clinical interview and the Childhood Trauma Questionnaire-Short Form (CTQ-SF) to describe the prevalence and association between trauma exposure during childhood with a severe course of illness (early age onset, rapid cycling, ideation or suicide attempt, or ≥ 3 hospitalization) in a sample of BD patients.

Results: A total of 114 cases and 191 controls evaluated showed the following results. Cases included 61.4% BD type I and 38.6% BD type II. The median age was 31.5 years (IQR, 75-24) for BD patients and 31 years old (IQR, 38-24) for healthy controls. A higher prevalence of childhood trauma was evidenced in cases compared to controls. Emotional abuse, physical abuse, sexual abuse, physical neglect and emotional neglect evidenced a strong association with severe bipolar disorder (OR = 3.42, p < .001; OR = 4.68, p < .001; OR = 4.30, p = .003; OR = 5.10, p < .001; OR = 5.64, p < .001, respectively).

Conclusions: This is the first association study between childhood trauma exposure as a higher risk for a severe course of illness in BD patients in Colombian. Our findings highlight the higher prevalence of childhood trauma in bipolar patients and the strong association of childhood trauma with severe bipolar disorder. These findings are relevant for screening and evaluating childhood trauma exposure during the course of BD patients.