Posttraumatic stress disorder is a serious and often disabling syndrome that develops in response to a traumatic event. Many individuals who initially develop the disorder go on to experience a chronic form of the condition that in some cases can last for many years. Among these patients, psychiatric and medical comorbidities are common, including early onset of age-related conditions such as chronic pain, cardiometabolic disease, neurocognitive disorders, and dementia. The hallmark symptoms of posttraumatic stress-recurrent sensory-memory reexperiencing of the trauma(s)-are associated with concomitant activations of threat- and stress-related neurobiological pathways that occur against a tonic backdrop of sleep disturbance and heightened physiological arousal. Emerging evidence suggests that the molecular consequences of this stress-perpetuating syndrome include elevated systemic levels of oxidative stress and inflammation. In this article we review evidence for the involvement of oxidative stress and inflammation in chronic PTSD and the neurobiological consequences of these processes, including accelerated cellular aging and neuroprogression. Our aim is to update and expand upon previous reviews of this rapidly developing literature and to discuss magnetic resonance spectroscopy as an imaging technology uniquely suited to measuring oxidative stress and inflammatory markers in vivo. Finally, we highlight future directions for research and avenues for the development of novel therapeutics targeting oxidative stress and inflammation in patients with PTSD.

Background Posttraumatic stress disorder (PTSD) is a psychiatric disorder characterized by debilitating re-experiencing, avoidance, and hyperarousal symptoms following trauma exposure. Recent evidence suggests that individuals with PTSD show disrupted functional connectivity in the default mode network, an intrinsic network that consists of a midline core, a medial temporal lobe (MTL) subsystem, and a dorsomedial prefrontal cortex (dMPFC) subsystem. The present study examined whether functional connectivity in these subsystems is differentially disrupted in PTSD. Methods Sixty-nine returning war Veterans with PTSD and 44 trauma-exposed Veterans without PTSD underwent resting state functional MRI (rs-fMRI). To examine functional connectivity, seeds were placed in the core hubs of the default mode network, namely the posterior cingulate cortex (PCC) and anterior medial PFC (aMPFC), and in each subsystem. Results Compared to controls, individuals with PTSD had reduced functional connectivity between the PCC and the hippocampus, a region of the MTL subsystem. Groups did not differ in connectivity between the PCC and dMPFC subsystem or between the aMPFC and any region within either subsystem. In the PTSD group, connectivity between the PCC and hippocampus was negatively associated with avoidance/numbing symptoms. Examination of the MTL and dMPFC subsystems revealed reduced anticorrelation between the ventromedial PFC (vMPFC) seed of the MTL subsystem and the dorsal anterior cingulate cortex in the PTSD group. Conclusions Our results suggest that selective alterations in functional connectivity in the MTL subsystem of the default mode network in PTSD may be an important factor in PTSD pathology and symptomatology.

Smaller hippocampal volume has been consistently observed as a biomarker of posttraumatic stress disorder (PTSD). However, less is known about individual volumes of the subfields composing the hippocampus such as the dentate gyrus and cornu ammonis (CA) fields 1-4 in PTSD. The aim of the present study was to examine the hypothesis that volume of the dentate gyrus, a region putatively involved in distinctive encoding of similar events, is smaller in individuals with PTSD versus trauma-exposed controls. Ninety-seven recent war veterans underwent structural imaging on a 3T scanner and were assessed for PTSD using the Clinician-Administered PTSD Scale. The hippocampal subfield automated segmentation program available through FreeSurfer was used to segment the CA4/dentate gyrus, CA1, CA2/3, presubiculum, and subiculum of the hippocampus. Results showed that CA4/dentate gyrus subfield volume was significantly smaller in veterans with PTSD and scaled inversely with PTSD symptom severity. These results support the view that dentate gyrus abnormalities are associated with symptoms of PTSD, although additional evidence is necessary to determine whether these abnormalities underlie fear generalization and other memory alterations in PTSD.