Trauma-altered immune activation via elevated hs-CRP in patients with SZ and BD may be mediated by higher BMI; however, the direction of this association needs further clarification.

Background: The neural diathesis-stress model is useful to understand schizophrenia (SZ) and bipolar (BD) disorders. Childhood maltreatment could affect the Hypothalamic-Pituitary-Adrenal (HPA)-axis and lead to chronic changes in stress-sensitivity, which can be measured with hair cortisol concentrations (HCC), representing long-term, cumulative cortisol levels. Here we investigated if childhood trauma experiences are associated with chronic changes in the HPA axis in severe mental disorders. Methods: Participants with SZ or BD (N=63) and healthy controls (N=94) were included, and HCC was measured by ELISA. History of childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ). Global function and symptom levels were obtained using the Global Assessment of Functioning (GAF) Scale and the Positive and Negative Syndrome Scale (PANSS). A neuropsychological test battery (MATRICS) was performed to assess cognitive functions. Results: Our study shows for the first time that patients with a history of childhood maltreatment have higher HCC relative to both healthy controls and patients without a history of childhood maltreatment (P=0.01, ƞp 2 =0.046). In addition, patients experiencing a mood episode had higher HCC than patients in remission (P=0.03). Lastly, we are the first to show that patients with higher HCC had poorer cognitive performance, specifically working memory (P=0.01). All associations were irrespective of diagnostic group. A factor analysis confirmed a subgroup within the patients characterized by childhood maltreatment and elevated HCC. Conclusions: Findings support the neural diathesis-stress model in SZ and BD pointing to long-term changes in HPA-axis following childhood maltreatment experiences.

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