Hippocampal subfield alterations in pediatric patients with post-traumatic stress disorder

The hippocampus, a key structure with distinct subfield functions, is strongly implicated in the pathophysiology of post-traumatic stress disorder (PTSD); however, few studies of hippocampus subfields in PTSD have focused on pediatric patients. We therefore investigated the hippocampal subfield volume using an automated segmentation method and explored the subfield-centered functional connectivity aberrations related to the anatomical changes, in a homogenous population of traumatized children with and without PTSD. To investigate the potential diagnostic value in individual patients, we used a machine learning approach to identify features with significant discriminative power for diagnosis of PTSD using random forest classifiers. Compared to controls, we found significant mean volume reductions of 8.4% and 9.7% in the right presubiculum and hippocampal tail in patients, respectively. These two subfields' volumes were the most significant contributors to group discrimination, with a mean classification accuracy of 69% and a specificity of 81%. These anatomical alterations, along with the altered functional connectivity between (pre)subiculum and inferior frontal gyrus, may underlie deficits in fear circuitry leading to dysfunction of fear extinction and episodic memory, causally important in post-traumatic symptoms such as hypervigilance and re-experience. For the first time, we suggest that hippocampal subfield volumes might be useful in discriminating traumatized children with and without PTSD.