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Introduction: A significant proportion of adults with depressive or bipolar disorders exposed to early adverse stressors do not adequately respond to standard treatments. This review aimed at synthesizing the evidence on the effectiveness of treatment interventions for depressive or bipolar disorders in adult individuals (aged 18 years or more) exposed to adverse stress early in life. Methods: Systematic review and meta-analysis including experimental and quasi-experimental published studies indexed in CINAHL, EMBASE, PubMed, and Web of Science databases and/or in reference lists. Data management and critical appraisal (with the Study Quality Assessment Tools) was conducted independently by multiple researchers. A quality-effects model for meta-analysis was used for data synthesis and publication bias was assessed using the Doi plot and LFK index. The main outcome was short-term reductions in depressive symptoms. Results: Eight randomized controlled trials, three controlled before-and-after (pre-post) studies, and three uncontrolled before-and-after studies were included. Studies lacked bipolar disorder patients. Unclear randomization procedures and reporting of blinded outcome assessor, and limited use of intention-to-treat analysis, were relevant potential sources of bias. Meta-analyses indicated that psychological, pharmacological, and combined interventions were effective in reducing depressive symptoms in the short- (Cohen's d = -0.55, 95% CI -0.75 to -0.36, I 2 = 0%) and mid-term (Cohen's d = -0.66, 95% CI -1.07 to -0.25, I 2 = 65.0%). However, a high risk of publication bias was detected for these outcomes. A small number of studies, with mixed results, reported interventions with long-term improvements in depressive symptomatology, and short- and mid-term response to treatment and remission. Conclusion: Despite the well-documented long-lasting, negative, and costly impact of early adverse stressors on adult psychopathology, evidence on treatment alternatives remains scant. Trauma-focused treatment interventions-whether psychological interventions alone or in combination with pharmacotherapy-may have the potential to reduce the severity of depressive symptom in adults who were exposed to early adverse stress. Findings must be interpreted with considerable caution, as important study and outcome-level limitations were observed and gray literature was not considered in this systematic review and meta-analysis.
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OBJECTIVE: The authors investigated the associations between polygenic liability and progression to bipolar disorder or psychotic disorders among individuals diagnosed with unipolar depression in early life. METHODS: A cohort comprising 16,949 individuals (69% female, 10-35 years old at the first depression diagnosis) from the iPSYCH Danish case-cohort study (iPSYCH2012) who were diagnosed with depression in Danish psychiatric hospitals from 1994 to 2016 was examined. Polygenic risk scores (PRSs) for major depression, bipolar disorder, and schizophrenia were generated using the most recent results from the Psychiatric Genomics Consortium. Hazard ratios for each disorder-specific PRS were estimated using Cox regressions with adjustment for the other two PRSs. Absolute risk of progression was estimated using the cumulative hazard. RESULTS: Patients were followed for up to 21 years (median=7 years, interquartile range, 5-10 years). The absolute risks of progression to bipolar disorder and psychotic disorders were 7.3% and 13.8%, respectively. After mutual adjustment for the other PRSs, only the PRS for bipolar disorder predicted progression to bipolar disorder (adjusted hazard ratio for a one-standard-deviation increase in PRS=1.11, 95% CI=1.03, 1.21), and only the PRS for schizophrenia predicted progression to psychotic disorders (adjusted hazard ratio=1.10, 95% CI=1.04, 1.16). After adjusting for PRSs, parental history still strongly predicted progression to bipolar disorder (adjusted hazard ratio=5.02, 95% CI=3.53, 7.14) and psychotic disorders (adjusted hazard ratio=1.63, 95% CI=1.30, 2.06). CONCLUSIONS: PRSs for bipolar disorder and schizophrenia are associated with risk for progression to bipolar disorder or psychotic disorders, respectively, among individuals diagnosed with depression; however, the effects are small compared with parental history, particularly for bipolar disorder.