The neuropathology of bipolar disorder: systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Harrison PJ
PROVIDER: S-EPMC6292507 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Calcium signalling has long been implicated in bipolar disorder, especially by reports of altered intracellular calcium ion concentrations ([Ca2+]). However, the evidence has not been appraised critically. We carried out a systematic review and meta-analysis of studies of cellular calcium indices in bipolar disorder. 2281 records were identified and 117 screened, of which 32 were eligible and 21 were suitable for meta-analyses. The latter each involved up to 642 patients and 404 control subjects. We found that basal free intracellular [Ca2+] is increased in bipolar disorder, both in platelets and in lymphocytes. The effect size is 0.55, with an estimated elevation of 29%. It is observed in medication-free patients. It is present in mania and bipolar depression, but data are equivocal for euthymia. Cells from bipolar disorder individuals also show an enhanced [Ca2+] response to stimulation with 5-HT or thrombin, by an estimated 25%, with an effect size of 0.63. In studies which included other diagnoses, intracellular basal [Ca2+] was higher in bipolar disorder than in unipolar depression, but not significantly different from schizophrenia. Functional parameters of cellular Ca2+ (e.g. calcium transients), and neuronal [Ca2+], have been much less investigated, and no firm conclusions can be drawn. In summary, there is a robust, medium effect size elevation of basal and stimulated free intracellular [Ca2+] in bipolar disorder. The results suggest altered calcium functioning in the disorder, and encourage further investigations into the underlying mechanisms, and the implications for pathophysiology and therapeutics.
| S-EPMC8550977 | biostudies-literature
Project description:OBJECTIVE:To determine clinical predictors of lithium response in bipolar disorder. METHODS:Systematic review of studies examining clinical predictors of lithium response was conducted. Meta-analyses were performed when ≥2 studies examined the same potential predictor. RESULTS:A total of 71 studies, including over 12 000 patients, identified six predictors of good response: mania-depression-interval sequence [odds ratio (OR): 4.27; 95% CI: 2.61, 6.97; P < 0.001], absence of rapid cycling (OR for rapid cycling: 0.30; 95% CI: 0.17, 0.53; P < 0.001), absence of psychotic symptoms (OR for psychotic symptoms: 0.52; 95% CI: 0.34, 0.79; P = 0.002), family history of bipolar disorder (OR: 1.61; 95% CI: 1.03, 2.52; P = 0.036), shorter prelithium illness duration [standardised mean difference (SMD): -0.26; 95% CI: -0.41, -0.12; P < 0.001] and later age of onset (SMD: 0.17; 95% CI: 0.02, 0.36; P = 0.029). Additionally, higher body mass index was associated with poor response in two studies (SMD: -0.61; 95% CI: -0.90, -0.32; P < 0.001). There was weak evidence for number of episodes prior to lithium treatment (SMD: -0.42; 95% CI: -0.84, -0.01; P = 0.046), number of hospitalisations before lithium (SMD: -0.40; 95% CI: -0.81, 0.01; P = 0.055) and family history of lithium response (OR: 10.28; 95% CI: 0.66, 161.26; P = 0.097). CONCLUSIONS:The relative importance of these clinical characteristics should be interpreted with caution because of potential biases and confounding.
| S-EPMC6772083 | biostudies-other
Project description:BACKGROUND:Bipolar disorder (BD) is a major psychiatric illness, however its physiopathology is unclear. The role of folate in the physiopathology of BD is controversial. We conducted this systematic review and meta-analysis to investigate the effect of folate in BD patients. METHODS:We performed a thorough literature study of the PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane Library, ProQuest, Web of Science, and ClinicalTrials.gov databases until December 21st, 2018. Random effects meta-analysis was conducted. RESULTS:Six articles involving 481 patients with BD and 760 controls were included. The meta-analysis results suggested that serum folate levels in the patients with BD were significantly lower than those in the controls (Hedges' g = - 0.211, 95% confidence interval = - 0.391 to - 0.031, p = 0.021). CONCLUSION:The current meta-analysis show it might be association between lower serum folate levels and patient with BD. However, we could not distinguish the potentially confounding effects of mood states on the folate levels. Further prospective studies including subjects with different mood states and possible physiopathology are warranted to investigate the association between folate deficiency and the etiology of BD.
| S-EPMC6805488 | biostudies-literature
Project description:BackgroundPrepulse inhibition (PPI) is a measurement method for the sensory gating process, which helps the brain adapt to complex environments. PPI may be reduced in patients with bipolar disorder (BD). This study investigated PPI deficits in BD and pooled the effect size of PPI in patients with BD.MethodsWe conducted a literature search on PPI in patients with BD from inception to July 27, 2019 in PubMed, Embase, Cochrane Library databases, and Chinese databases. No age, sex, and language restriction were set. The calculation formula was PPI = 100 - [100*((prepulse - pulse amplitude) / pulse amplitude)]. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies.ResultsTen eligible papers were identified, of which five studies including a total of 141 euthymic patients and 132 healthy controls (HC) were included in the meta-analysis. Compared with HC, euthymic patients with BD had significantly lower PPI at the 60 ms interstimulus interval (ISI) between pulse and prepulse (P = 0.476, I2 = 0.0%, SMD = - 0.32, 95% CI = - 0.54 - -0.10). Sensitivity analysis shows no significant change in the combined effect value after removing any single study. There was no publication bias using the Egger's test at 60 ms (P = 0.606). The meta-analysis of PPI at the 60 ms ISI could have significant clinical heterogeneity in mood episode state, as well as lack of data on BD I or II subtypes.ConclusionsEuthymic patients with BD show PPI deficits at the 60 ms, suggesting a deficit in the early sensory gate underlying PPI. The PPI inhibition rate at a 60 ms interval is a stable index. More research is needed in the future to confirm this outcome, and to delve deeper into the mechanisms behind deficits.
| S-EPMC6737635 | biostudies-literature
Project description:ImportanceSeveral psychotherapy protocols have been evaluated as adjuncts to pharmacotherapy for patients with bipolar disorder, but little is known about their comparative effectiveness.ObjectiveTo use systematic review and network meta-analysis to compare the association of using manualized psychotherapies and therapy components with reducing recurrences and stabilizing symptoms in patients with bipolar disorder.Data sourcesMajor bibliographic databases (MEDLINE, PsychInfo, and Cochrane Library of Systematic Reviews) and trial registries were searched from inception to June 1, 2019, for randomized clinical trials of psychotherapy for bipolar disorder.Study selectionOf 3255 abstracts, 39 randomized clinical trials were identified that compared pharmacotherapy plus manualized psychotherapy (cognitive behavioral therapy, family or conjoint therapy, interpersonal therapy, or psychoeducational therapy) with pharmacotherapy plus a control intervention (eg, supportive therapy or treatment as usual) for patients with bipolar disorder.Data extraction and synthesisBinary outcomes (recurrence and study retention) were compared across treatments using odds ratios (ORs). For depression or mania severity scores, data were pooled and compared across treatments using standardized mean differences (SMDs) (Hedges-adjusted g using weighted pooled SDs). In component network meta-analyses, the incremental effectiveness of 13 specific therapy components was examined.Main outcomes and measuresThe primary outcome was illness recurrence. Secondary outcomes were depressive and manic symptoms at 12 months and acceptability of treatment (study retention).ResultsA total of 39 randomized clinical trials with 3863 participants (2247 of 3693 [60.8%] with data on sex were female; mean [SD] age, 36.5 [8.2] years) were identified. Across 20 two-group trials that provided usable information, manualized treatments were associated with lower recurrence rates than control treatments (OR, 0.56; 95% CI, 0.43-0.74). Psychoeducation with guided practice of illness management skills in a family or group format was associated with reducing recurrences vs the same strategies in an individual format (OR, 0.12; 95% CI, 0.02-0.94). Cognitive behavioral therapy (SMD, -0.32; 95% CI, -0.64 to -0.01) and, with less certainty, family or conjoint therapy (SMD, -0.46; 95% CI, -1.01 to 0.08) and interpersonal therapy (SMD, -0.46; 95% CI, -1.07 to 0.15) were associated with stabilizing depressive symptoms compared with treatment as usual. Higher study retention was associated with family or conjoint therapy (OR, 0.46; 95% CI, 0.26-0.82) and brief psychoeducation (OR, 0.44; 95% CI, 0.23-0.85) compared with standard psychoeducation.Conclusions and relevanceThis study suggests that outpatients with bipolar disorder may benefit from skills-based psychosocial interventions combined with pharmacotherapy. Conclusions are tempered by heterogeneity in populations, treatment duration, and follow-up.
| S-EPMC7557716 | biostudies-literature
Project description:Objective: To estimate overall prevalence of bipolar disorder (BD) and the prevalence and timing of bipolar-spectrum mood episodes in perinatal women.Data Sources: Databases (PubMed, Scopus, PsycINFO, CINAHL, Cochrane, ClincalTrials.gov) were searched from inception to March 2020.Study Selection: Included studies were original research in English that had (1) populations of perinatal participants (pregnant or within 12 months postpartum), aged ≥ 18 years, and (2) a screening/diagnostic tool for BD. Search terms described the population (eg, perinatal), illness (eg, bipolar disorder), and detection (eg, screen, identify).Data Extraction: Study design data, rates, and timing of positive screens/diagnoses and mood episodes were extracted by 3 independent reviewers. Pooled prevalences were estimated using random-effects meta-analyses.Results: Twenty-two articles were included in qualitative review and 12 in the meta-analysis. In women with no known psychiatric illness preceding the perinatal period, pooled prevalence of BD was 2.6% (95% CI, 1.2%-4.5%) and prevalence of bipolar-spectrum mood episodes (including depressed, hypomanic/manic, mixed) during pregnancy and the postpartum period was 20.1% (95% CI, 16.0%-24.5%). In women with a prior BD diagnosis, 54.9% (95% CI, 39.2%-70.2%) were found to have at least one bipolar-spectrum mood episode occurrence in the perinatal period.Conclusions: Our review suggests that the perinatal period is associated with high rates of bipolar-spectrum mood episodes and that pregnant and postpartum women represent a special risk population. This review may help to inform clinical care recommendations, thus helping to identify those who may have.
| S-EPMC10849873 | biostudies-literature
Project description:Importance:Parkinson disease (PD) manifests by motor and nonmotor symptoms, which may be preceded by mood disorders by more than a decade. Bipolar disorder (BD) is characterized by cyclic episodes of depression and mania. It is also suggested that dopamine might be relevant in the pathophysiology of BD. Objective:To assess the association of BD with a later diagnosis of idiopathic PD. Data Sources:An electronic literature search was performed of Cochrane Controlled Register of Trials, MEDLINE, Embase, and PsycINFO from database inception to May 2019 using the terms Parkinson disease, bipolar disorder, and mania, with no constraints applied. Study Selection:Studies that reported data on the likelihood of developing PD in BD vs non-BD populations were included. Two review authors independently conducted the study selection. Data Extraction and Synthesis:Two review authors independently extracted study data. Data were pooled using a random-effects model, results were abstracted as odds ratios and 95% CIs, and heterogeneity was reported as I2. Main Outcome and Measures:Odds ratios of PD. Results:Seven studies were eligible for inclusion and included 4?374?211 participants overall. A previous diagnosis of BD increased the likelihood of a subsequent diagnosis of idiopathic PD (odds ratio, 3.35; 95% CI, 2.00-5.60; I2?=?92%). A sensitivity analysis was performed by removing the studies that had a high risk of bias and also showed an increased risk of PD in people with BD (odds ratio, 3.21; 95% CI, 1.89-5.45; I2?=?94%). Preplanned subgroup analyses according to study design and diagnostic certainty failed to show a significant effect. Conclusions and Relevance:This review suggests that patients with BD have a significantly increased risk of developing PD compared with the general population. Subgroup analyses suggested a possible overestimation in the magnitude of the associations. These findings highlight the probability that BD may be associated with a later development of PD and the importance of the differential diagnosis of parkinsonism features in people with BD.
| S-EPMC6802493 | biostudies-literature
Project description:BackgroundNon-adherence is a significant problem in bipolar disorder. Second-generation antipsychotics (SGA) long-acting injections (LAIs) may improve adherence in bipolar disorder and may prevent relapses. However, the evidence is limited and conflicting.ObjectiveThe objective of this study was to evaluate efficacy and safety of SGA LAIs in bipolar disorder.MethodSystematic review and meta-analysis of randomised controlled trials (RCTs) (≥6 months duration) investigating safety and efficacy of SGA LAIs for bipolar disorder. We searched Pubmed, Embase, CINAHL, Cochrane, PsycINFO, LiLACS, www.clinicaltrials.gov up to October 2016. We also contacted the manufacturers of SGA LAIs. Primary efficacy and safety outcomes were relapse rate and all-cause discontinuation respectively.ResultsTotal of seven RCTs (n = 1192) were included. SGA LAIs show superiority over placebo for study-defined relapse rate (RR = 0.58, 95% CI = 0.49-0.68, P < 0.00001) and all-cause discontinuation (RR = 0.72, 95% CI = 0.64-0.82, P < 0.00001). However, no significant difference was found between SGA LAIs and oral active control for relapse rate (RR = 0.92, P = 0.79) and all-cause discontinuation (RR = 1.2, P = 0.31). In terms of secondary outcomes, SGA LAIs performed better than placebo in relapse to mania/hypomania, young mania rating scales (YMRS), clinical global impression-severity (CGI-S), montgomery-asberg depression rating scale (MADRS). There was no significant difference between SGA LAIs and oral active control regarding relapse to mania/hypomania, YMRS, CGI-S, extra-pyramidal side effects (EPSEs), weight gain. However, the active control performed better than SGA LAIs in relapse to depression, MADRS, and prolactin-related AEs.ConclusionsCurrent evidence is very limited to support the use of SGA LAIs (compared to oral medication) in bipolar disorder. Further high-quality studies, particularly comparing SGA LAIs with active control, are warranted.
| S-EPMC6587954 | biostudies-literature
Project description:BACKGROUND:Bipolar disorder (BD) is a common severe mental disorder among homeless people and is associated with an increased risk of disability and mortality from suicide, medical causes (including HIV/AIDS, hepatitis infection, hypertension, and tuberculosis), as well as substance use disorders. However, a systematic synthesis of the existing evidence on the subject is lacking. To fill this gap in the literature, this study aimed to carry out systematic review and meta-analysis to determine the consolidated prevalence of BD among homeless people. METHODS:In this systematic review and meta-analysis, we searched Embase, PubMed, and Scopus to identify pertinent studies that reported the prevalence of BD among homeless people in March 2019. Random effect meta-analysis was employed to pool data from the eligible studies. Subgroup and sensitivity analysis was conducted and Cochran's Q- and the I2 test were utilized to quantify heterogeneity. Publication bias was assessed by using Egger's test and visual inspection of the symmetry in funnel plots. RESULTS:Of 3236 studies identified, 10 studies with 4300 homeless individuals were included in the final analysis. Among the 10 studies, five studies used the Diagnostic Statistical Manual of Mental disorders (DSM), three studies used Mini-International Neuropsychiatric Interview (MINI), one study used Schedule for Clinical Assessment of Neuropsychiatry (SCAN), and one study used Composite International Neuropsychiatric Interview (CIDI) to assess BD among homeless individuals. Based on the results of the random effect model, the prevalence of BD among homeless people was 11.4% (95% CI; 7.5-16.9). The prevalence of BD was 10.0% (95% CI; 3.1-27.9) in Europe and it was 13.2% (95% CI; 8.9-19.3) in other countries. Moreover, the prevalence of BD was 11.5% (95% CI; 5.5-22.3) for studies that used DSM to assess BD and it was 11.0% (95% CI; 6.1-19.2) for studies that used other instruments (MINI, SCAN, and CIDI). CONCLUSION:Our meta-analysis demonstrated that BD is highly prevalent among homeless individuals, underlying the importance of early screening and targeted interventions for BD among homeless individuals.
| S-EPMC7282102 | biostudies-literature
Project description:ObjectiveWe carried out a systematic review and meta-analysis to evaluate whether history of bipolar disorder (BD) increases the risk of dementia.MethodsWe searched PubMed and Scopus to identify studies that evaluated the risk of dementia in individuals with a history of BD. A total of 6 studies including 3,026 individuals with history of BD and 191,029 non-BD individuals were included in the meta-analysis.ResultsHistory of BD significantly increased the risk of diagnosis of dementia (pooled odds ratio: 2.36; 95% confidence interval: 1.36-4.09; z = 3.07, p < 0.001). Evidence of heterogeneity and of publication bias in the analysis was found.ConclusionHistory of BD is associated with significantly higher risk of dementia in older adults. Future studies are necessary to evaluate the potential mediators of this association and to evaluate interventions that may reduce the risk of dementia in this population.
| S-EPMC5365367 | biostudies-literature