Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: A meta-analysis of structural MRI studies

Over the last decade a significant number of studies have reported smaller hippocampal volume in individuals with symptoms of post-traumatic stress disorder (PTSD) relative to control groups, and in some cases hemispheric asymmetries in this effect have been noted. However these reported asymmetries have not been in a consistent direction, and other well-controlled studies have failed to observe any hippocampal volume difference. This paper reports a systematic review and meta-analysis of studies in which hippocampal volume was estimated from magnetic resonance images in adult patients with PTSD. After applying a variety of selection criteria intended to minimize potential confounds in pooled effect-size estimates, the meta-analysis included 13 studies of adult patients with PTSD that compared the patients to well-matched control groups, for a total of 215 patients and 325 control subjects. The studies varied with respect to participant age, gender distribution, source of trauma, severity of symptoms, duration of disorder, the nature of the control groups, and the methods employed for volumetric quantification. Despite these differences, pooled effect size calculations across the studies indicated significant volume differences in both hemispheres. On average PTSD patients had a 6.9% smaller left hippocampal volume and a 6.6% smaller right hippocampal volume compared with control subjects. These volume differences were smaller when comparing PTSD patients with control subjects exposed to similar levels of trauma, and larger when comparing PTSD patients to control subjects without significant trauma exposure. Such differences are consistent with the notion that exposure to stressful experiences can lead to hippocampal atrophy, although prospective studies would be necessary to unambiguously establish such a relationship.