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Background Childhood trauma is one of the most important risk factors in psychosis. Mounting evidence is associating early trauma exposure with alterations in stress sensitive areas, like the hippocampus, and abnormal concentrations of the main stress hormone, cortisol. As hippocampus is a pivotal brain region in the hypothalamus–pituitary–adrenal (HPA) axis regulation of cortisol, better understanding the relationship between childhood trauma, hippocampus structure and cortisol concentration would help clarify how childhood trauma exposure can increase the risk of developing psychosis later on in life. Methods Brain structure was evaluated with a 3T MRI scan in 86 first episode psychosis patients (FEP) (49 of which positive for severe childhood trauma) (mean age: 27.8 SD ± 9.1 years). Hippocampal volume and the segmentation of the hippocampal subfields was obtained using FreeSurfer 6. Salivary cortisol samples were collected to measure cortisol levels at awakening (CAR). Initially two separate linear regression models were ran: 1) to predict hippocampal volume changes with childhood trauma as the independent variable and 2) to predict hippocampal volume changes with CAR as independent variable. Finally, we introduced CAR as moderator in the linear model 1 to explore whether it changed the relationship between childhood abuse and hippocampal volume. Results Individuals with psychosis and severe childhood abuse presented smaller volume of the right hippocampal head (β = -108.9, p = 0.027), particularly in subfields CA1, CA3, CA4 and in the right GC-ML-DG head (all significant at p &amp;lt; 0.05 with βs between – 110 and -90) (linear model 1). CAR did not predict changes in hippocampal volumes (linear model 2). However, when CAR was introduced the relationship between childhood abuse and hippocampal volume (linear model 1) it showed a moderator role. Indeed low levels of CAR were associated with an even further reduction in hippocampal volume in the right hippocampal head and particularly in subfields CA1, CA3 and CA4 (all significant at p &amp;lt; 0.05 and βs between – 150 and -180). Discussion These results suggest that exposure to childhood trauma has a long-term effect on the adult brain particularly in hippocampal areas related to the encoding and retrieval of memories. Importantly, low levels of CAR are associated with even smaller hippocampal head in patients who childhood trauma This is particularly important, because an abnormal hippocampal structure could alter the hippocampal feedback on the HPA axis leading to dysfunctional (lower) cortisol production, which in turn would amplify the impact on brain stress sensitive regions of further stress exposure.

S186. THE EFFECTS OF CHILDHOOD TRAUMA ON HIPPOCAMPAL VOLUME IN FIRST EPISODE PSYCHOSIS: DOES CORTISOL PLAY A ROLE?