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

• Authors: Jony Sheynin, Vet Affairs Ann Arbor Healthcare Syst; Elizabeth R Duval, Vet Affairs Ann Arbor Healthcare Syst; Anthony P King, Vet Affairs Ann Arbor Healthcare Syst; Mike Angstadt, University of Michigan; Luan K Phan, Ohio State University; Naomi M Simon, Massachusetts General Hospital; Sheila Rauch, Emory University; Israel Liberzon, Vet Affairs Ann Arbor Healthcare Syst
• Journal Title: DEPRESSION AND ANXIETY
• Volume: Volume 37, Number 10
• Publisher: WILEY | 2020-07-15, Pages 1037-1046
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/da.23075
• Subjects: Health Sciences, Mental Health
• Keywords: Social Sciences; Science & Technology; Life Sciences & Biomedicine; Psychology, Clinical; Psychiatry; Psychology; fMRI; functional connectivity; prolonged exposure; PTSD; resting state; sertraline; NETWORK CONNECTIVITY; DYSREGULATION; PSYCHOTHERAPY; ATTENTION; VETERANS; EXPOSURE

Abstract

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.