Daruy‐Filho L, Brietzke E, Lafer B, Grassi‐Oliveira R. Childhood maltreatment and clinical outcomes of bipolar disorder.Objective:  Adverse life events, especially early trauma, play a major role in the course and expression of bipolar disorder (BD). The aim of this article is to present a systematic review about the impact of childhood trauma on the clinical course of BD.Method:  A computer‐aided search was performed in Medline, ISI database, EMBASE, PsychInfo, Centre for Reviews and Dissemination, and Databases of Thomson Reuters at April 2011, supplemented by works identified from the reference lists of the first selected papers. Two investigators systematically and independently examined all articles, selecting those according inclusion and exclusion criteria.Results:  Four hundred fifteen articles were identified, of which 19 remained in the review after exclusion criteria were applied. In general, childhood maltreatment predicted worsening clinical course of BD. After assessing the quality of the data and of the measurements, childhood maltreatment can be strongly associated to early onset of disorder, suicidality, and substance abuse disorder in patients with BD.Conclusion:  Data suggest that childhood abuse and neglect are risk factors associated with worsening clinical course of BD. The conclusions should be interpreted with caution because all the studies included are cross‐sectional and the majority are showing inconsistencies regarding childhood trauma as independent variable and how it is assessed.

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Early-life stress (ELS) increases the risk for psychopathology. Immune and endocrine changes have been reported in adults and are associated with maladaptation of stress-responsive systems. Here we investigated the effects of ELS on endocrine and immune pathways in adolescents without psychopathology. Thirty adolescents with a history of childhood maltreatment and 27 adolescents without ELS history were recruited. Blood and hair samples were obtained from all participants. Lymphocytes were isolated and stimulated in vitro. Flow cytometry was used to evaluate lymphocyte subsets, Th1/Th2/Th17 cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB) signaling pathways, as well as lymphocyte sensitivity to dexamethasone. Brain-derived neurotrophic factor (BDNF) and hair cortisol were assessed with enzyme-linked immunosorbent assays (ELISAs). Adolescents with a history of ELS had increased percentages of T-cell activation markers (CD3+CD4+CD25+ and CD3+CD69+) and senescent T cells (CD8+CD28- and CD4+CD28-), as well as decreased percentages of NK (CD3-CD56+) and NK T cells (CD3+CD56+). Following stimulation, lymphocytes of ELS+ adolescents produced significantly more IL-2, IL-4, IFN-γ, and IL-17 and engaged more MAPK ERK and NF-κB signaling. ELS was associated with increased hair cortisol levels in parallel with increased lymphocyte resistance to dexamethasone and low plasma BDNF levels. These data provide the first indication of the presence of immune activation and pro-inflammatory profiles in healthy adolescents exposed to ELS, which could contribute to increased vulnerability of trauma-related psychopathology later in life. The underlying mechanisms of this impairment may include the enhanced activation of both MAPK and NF-κB signaling in parallel to partial resistance to glucocorticoids.

This study is the first to investigate HPA axis functioning using hair cortisol concentrations among crack cocaine-dependent users. It is a promising strategy to assess stress load in substance abusers.

Bipolar disorder (BD) is a prevalent and highly disabling psychiatric condition. Despite the widely acknowledged importance of psychosocial interventions that involve a complex cognitive, behavioral, and biological process to help patients cope better with their illness, few studies have systematically evaluated coping in BD. Therefore, our objective was to examine recent developments in current research on coping in BD. Several studies have documented a strong association between BD and numerous neuroanatomical and neuropsychological abnormalities, particularly multiple episodes and longer durations of the disorder. The most marked effects of BD encompass brain areas involved in executive function, which may affect the mechanisms underlying an adequate selection of coping strategies. Thus, the ability of individuals to reduce their own stress burden is impaired, increasing vulnerability to stressful life events and negatively affecting the course of BD. Psychosocial interventions that focus on BD should be evaluated for their ability to improve coping abilities, and research on BD should consider neuropsychological impairment and cognitive-behavioral strategies for coping with stress.