Associations between resting‐state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder

Background Alterations in resting‐state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre‐ and post‐treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. Methods Sixty‐four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting‐state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty‐nine trauma‐exposed combat veterans without PTSD served as a control group at intake. Seed‐based and region of interest (ROI)‐to‐ROI connectivities, as well as an exploratory connectome‐based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default‐Mode Network (DMN). Results At intake, patients with PTSD showed greater DMN–dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family‐wise error corrected p  = .011), greater SN–DAN connectivity (between insula and middle frontal gyrus; corrected p  = .003), and a negative correlation between re‐experiencing symptoms and within‐DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p  < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN–DMN segregation (i.e., less pre‐treatment amygdala–PCC connectivity; p  = .011) and lower pre‐treatment global centrality ( p  = .042). Conclusions Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.