Hippocampus is a temporal lobe structure implicated in learning and memory processing as well as in emotion processing, contextual processing, stress regulation, and more [11, 42, 119, 147]. PTSD symptoms had been also associated with deficits in memory function and negative emotion processing [11], implicating hippocampus in PTSD-related pathophysiology. Accordingly, abnormal activation of the hippocampus had been suggested by functional MRI studies of PTSD patients, as compared to trauma-exposed and healthy control subjects (reviewed by [80, 112]). Multiple structural MRI studies thus examined the hippocampal volume and VBM in diverse cohorts of adult PTSD patients including survivors of combat, physical/sexual abuse, disasters, and childhood maltreatment. The majority of volumetric studies reported smaller left, right, or bilateral hippocampal volumes in PTSD patients [7–10, 15, 17, 36, 47, 50, 57, 76, 82–84, 88, 109, 111, 120, 127, 139, 140, 144, 146, 149, 157]. In contrast, a smaller but meaningful number of studies failed to find difference in hippocampal volume in PTSD [6, 40, 48, 52, 53, 59, 117, 126, 156]. The meta-analyses published to date in general confirm smaller hippocampal volume in PTSD patients [61, 78, 107, 125], and the most recent largest meta-analysis examining neuroimaging and clinical data from 1868 subjects across 16 cohorts confirmed the presence of smaller hippocampus in PTSD [87]. Studies of the size of the subdivisions of hippocampus suggest that the dentate gyrus and adjacent anterior hippocampus specifically might be smaller in PTSD patients [140, 143]. Furthermore, some studies had found that hippocampal volume is smaller in veterans with current PTSD as compared to veterans with remitted PTSD, potentially suggesting that the hippocampal volume may be associated with the presence of active PTSD symptoms [17]. In concert, VBM-based studies also reported decreased gray matter density in hippocampal regions in PTSD patients [36, 39, 62, 77, 129, 130].

These structural findings were met with substantial interest because the convergence of functional and structural MRI findings suggests that the hippocampus may play a role in PTSD development. With respect to the functional significance of the volumetric findings, several studies reported relationships between hippocampal volume and the severity of PTSD symptoms, especially reexperiencing or dissociative symptoms [8, 39, 47, 82, 83, 127, 134, 139, 140, 144]. Furthermore, it has been also reported that in PTSD veterans, a smaller right hippocampal volume was positively correlated with deficits in short-term verbal memory, suggesting that alterations of hippocampal structure may be related to the memory functions of PTSD patients [8]. Interestingly, more recent data suggested that these findings might be at least to some degree reversible, as some interventions may be able to alter the hippocampal volume of PTSD patients. For example, a SSRI treatment that increases hippocampal volume of PTSD patients also reduces PTSD symptoms and significantly improved verbal memory [137]. Similarly, cognitive behavioral therapy (CBT), which had been demonstrated as effective treatment for PTSD, also increased hippocampal and medial orbital frontal volume associated with the clinical symptom improvement in PTSD patient [76]. However, these relationships between reduction of hippocampal volume and memory function or PTSD symptoms have not been detected in other studies [40, 117, 143, 150]. Thus, existing findings linking the abnormalities of hippocampal structure to symptom levels in PTSD patients are yet to be firmly established, and additional work clarifying these relationships is needed. Further examination of these relationships carries promise to further advance current understanding of PTSD pathophysiology.