The relationship between cortisol reactivity and emotional brain function is differently moderated by childhood trauma, in bipolar disorder, schizophrenia and healthy individuals.

Childhood trauma is a risk factor for psychotic and mood disorders that is associated with abnormal hypothalamic-pituitary-adrenal (HPA) axis function in response to stress and abnormal social brain function. Here, we aimed to determine whether childhood trauma exposure would differently moderate associations between cortisol reactivity and social brain function, among cases with schizophrenia (SZ), bipolar disorder (BD) and in healthy individuals (HC). Forty cases with SZ, 35 with BD and 34 HCs underwent functional magnetic resonance imaging while performing an emotional face-matching task. Participants completed the Childhood Trauma Questionnaire and cortisol reactivity (i.e. the slope indexing the within-subject difference between pre- and post-imaging salivary cortisol levels) was determined. The severity of childhood trauma moderated the relationship between cortisol reactivity and brain activation in the bilateral temporo-parieto-insular junctions, right middle cingulum, right pre/postcentral gyri, left cerebellum and right lingual gyrus, differently depending on the clinical group. When exposed to high levels of trauma, the cortisol slope was negatively associated with activation in these regions in HC, while the cortisol slope was positively associated with activation in these regions in SZ cases. Similarly, there were differences between the groups in how trauma severity moderated the relationship between cortisol reactivity and functional connectivity between the amygdala and dorsolateral prefrontal cortex. In addition to reflecting typical associations between cortisol reactivity and emotional brain function when not exposed to childhood trauma, these findings provide new evidence that trauma exposure disrupts these relationships in both healthy individuals and in cases with SZ or BD.