Dynamic immune and metabolic dysregulation in women with post-traumatic stress disorder: Longitudinal transcriptomic...

Post-traumatic stress disorder (PTSD) is a chronic and debilitating psychiatric condition, and sexual assault represents the leading risk factor for PTSD in women, with up to 50% of survivors developing the disorder. However, most transcriptomic studies have focused on male military veterans, limiting insight into the molecular mechanisms underlying PTSD in women. We conducted a longitudinal RNA sequencing study of blood samples from 65 women with PTSD and 65 healthy controls (HC). One-year follow-up assessments were performed in 35 PTSD participants after completion of treatment with either sertraline or Interpersonal Psychotherapy adapted for PTSD (IPT-PTSD), and in 12 HC participants, who did not receive treatment but were reassessed for longitudinal comparison of transcriptomic profiles. Differential gene expression analyses were conducted across diagnostic groups (PTSD vs HC), symptom trajectories (persistent vs remitting), and treatment arms (sertraline vs IPT-PTSD), using both cross-sectional and longitudinal designs. Pathway enrichment and co-expression network analyses were performed to identify dysregulated biological processes and gene modules. At baseline, women with PTSD exhibited downregulation of immune-related pathways and upregulation of erythropoietic and metabolic processes compared to HC, consistent with systemic immune suppression and compensatory transcriptomic adaptations. Persistent PTSD was characterized by sustained immune suppression, dysregulated apoptotic signaling, and elevated mitochondrial activity, whereas the remitting trajectory showed upregulation of immune response and cell communication pathways, suggesting partial immune restoration. Comparing PTSD cases at baseline and after one year of treatment, both sertraline and IPT-PTSD were associated with overlapping transcriptomic changes, suggesting shared molecular mechanisms. Overall, this study reveals dynamic peripheral transcriptomic dysregulation in women with PTSD. Although we cannot fully disentangle whether these changes reflect the disorder itself or traumatic exposure, our findings identify molecular signatures of symptom persistence, remission, and treatment response, supporting the potential utility of transcriptomic biomarkers to inform therapeutic strategies.