Hippocampal atrophy in major depression: a function of childhood maltreatment rather than diagnosis?

Reduced hippocampal volumes are probably the most frequently reported structural neuroimaging finding associated with major depressive disorder (MDD). However, it remains unclear whether altered hippocampal structure represents a risk factor for or a consequence of MDD. Reduced hippocampal volumes were consistently reported in subjects affected by childhood maltreatment. As the prevalence of childhood maltreatment is highly elevated in MDD populations, previous morphometric findings regarding hippocampal atrophy in MDD therefore might have been confounded by maltreatment experiences. The aim of this study was to differentiate the impact of childhood maltreatment from the influence of MDD diagnosis on hippocampal morphometry. Depressed patients (85) as well as 85 age- and sex-matched healthy controls underwent structural MRI. The Childhood Trauma Questionnaire was administered to estimate experiences of childhood maltreatment. Hippocampal volume and surface structure was examined by the use of two independent methods, automated segmentation (FSL-FIRST) and voxel-based morphometry (VBM8). In line with existing studies, MDD patients showed reduced hippocampal volumes, and childhood maltreatment was consistently associated with hippocampal volume loss in both, patients and healthy controls. However, no analysis revealed significant morphological differences between patients and controls if maltreatment experience was regressed out. Our results suggest that hippocampal alterations in MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients.