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Childhood maltreatment is associated with a chronic inflammatory state independent of clinical comorbidities. However, studies are heterogeneous regarding CM assessment and definition. Important methodological improvements are needed to better understand the potential impact of CM on inflammatory response.

A model of staging in the field of bipolar disorder (BD) should offer a means for clinicians to predict response to treatment and more general outcome measures, such as the level of functioning and autonomy. The present staging model emphasizes the assessment of patients in the interepisodic period and includes: latent phase: individuals who present mood and anxiety symptoms and increased risk for developing threshold BD; Stage I--patients with BD who present well established periods of euthymia and absence of overt psychiatric morbidity between episodes; Stage II--patients who present rapid cycling or current axis I or II comorbidities; Stage III--patients who present a clinically relevant pattern of cognitive and functioning deterioration, as well as altered biomarkers; and Stage IV--patients who are unable to live autonomously and present altered brain scans and biomarkers. Such a model implies a longitudinal appraisal of clinical variables, as well as assessment of neurocognition and biomarkers in the interepisodic period. Staging facilitates understanding of the mechanisms underlying progression of the disorder, assists in treatment planning and prognosis and, finally, underscores the imperative for early intervention.

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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.

The questionnaire's Portuguese version proved to be easily understandable showing good semantic validation. Nevertheless, further studies should address other psychometric characteristics of this instrument.

Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2–21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population.

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