Childhood trauma and hippocampal subfield volumes in first-episode schizophrenia and healthy controls

Childhood trauma and schizophrenia are both associated with neuroanatomical abnormalities in the hippocampus, a stress-sensitive structure vulnerable to developmental insults. However, few studies have evaluated the effects of childhood trauma exposure on hippocampal morphometry in minimally treated first-episode schizophrenia patients. Here we aim to investigate the associations of childhood trauma with hippocampal subfield volumes in a cohort of antipsychotic-naive or minimally treated first-episode schizophrenia spectrum disorder patients and matched controls. 79 patients with first-episode schizophrenia spectrum disorder and 82 matched controls completed the childhood trauma questionnaire and underwent MRI assessment. Hippocampal subfields were reconstructed using FreeSurfer 6.0. We considered inter-correlations between the various subfields, by entering them as dependent variables into a multivariate analysis of co-variance (MANCOVA), modeling for interactions between diagnosis, childhood trauma total score and gender while controlling for substance use, scanner sequence and age. MANCOVA revealed a significant interaction between sex, childhood trauma total scores and diagnosis across hippocampal sub-regions (p = 0.012). Bonferroni corrected post-hoc analysis revealed a significant sex*diagnosis*childhood trauma score interaction for the hippocampal fissure (F(1,161) = 9.485,p = .002). Hippocampal fissure size showed a positive relationship with CA structures as well as whole hippocampal size in the larger sample. Findings from the present study suggest that childhood trauma exposure exerts illness-specific effects on hippocampal structures in female patients with first-episode schizophrenia, consistent with increased stress sensitivity in this group.