Neuromarkers of Post-Traumatic Stress Disorder: A Systematic Review of Positron Emission Tomography Studies

Introduction: Posttraumatic stress disorder (PTSD) is a severe mental health condition that can arise following exposure to a traumatic event. Identification of biomarkers using imaging techniques, such as positron emission tomography (PET) scans, offers an alternative to increasingly complex methods of diagnostic. This systematic review aims to assess and summarize evidence for PTSD molecular biomarkers. Methods Studies published before June 2025, examining brain changes using PET imaging in adult PTSD patients were retrieved from three electronic databases. Inclusion criteria included original articles on human studies, PTSD diagnosis, and inclusion of healthy controls (never exposed to trauma) and/or trauma-exposed controls who did not develop PTSD. Studies with incomplete reporting, non-English publications, and those lacking control groups were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale. Results After screening of the 1102 articles retrieved, 20 met the inclusion criteria. These involved 483 patients and 522 controls, including 426 trauma-exposed or 96 healthy controls. PTSD was associated with increased glucose metabolism in the amygdala and dorsal anterior cingulate cortex, alongside hypometabolism of the hippocampus and precuneus. Aberrant neurotransmitters, stress/inflammation systems, as well as elevated amyloid-beta accumulation, were also evident in PTSD patients. Conclusions This review highlights consistent neurobiological alterations in PTSD, including changes in metabolism, neurotransmission, and inflammation. These alterations predominantly involve large-scale brain networks such as the salience network, default mode network, and frontoparietal network, reflecting disruptions in emotional regulation, self-referential processing, and executive control. PET imaging shows promise for advancing diagnosis, monitoring treatment response, and informing personalized interventions.