Increased Neural Response to Trauma Scripts in Posttraumatic Stress Disorder Following Paroxetine Treatment: A Pilot Study

• Type of Material: Article
• Authors: Negar Fani, Emory University; Ali Ashraf, Emory University; Nadeem Afzal, Emory University; Farhan Jawed, Emory University; Noriyuki Kitayama, Emory University; Lai Reed, Emory University; J. Douglas Bremner, Emory University
• Language: English
• Date: 2011-03-24
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Published by Elsevier Ireland Ltd.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neulet.2011.01.037
• Title of Journal or Parent Work: Neuroscience Letters
• ISSN: 0304-3940
• Volume: 491
• Issue: 3
• Start Page: 196
• End Page: 201
• Grant/Funding Information: This study was supported by an Investigator Initiated Research Grant from GlaxoSmithKline and NIH research grants to JDB R01 HL088726, K24 MH076955, T32 MH067547-01, R01 MH56120, and the clinical interactions network (CIN) of the Atlanta Clinical and Translational Sciences Institute (ACTSI).

Abstract

Neuroimaging studies of individuals with posttraumatic stress disorder (PTSD) have revealed altered patterns of activity in medial prefrontal brain regions, including the anterior cingulate cortex (ACC), an area implicated in affect regulation. Selective serotonin reuptake inhibitors (SSRIs) have been shown to effectively treat PTSD symptoms, but there remains a lack of functional neuroimaging research examining the effects of psychopharmacological treatment on brain function in PTSD. The purpose of this pilot study was to assess the effects of the SSRI paroxetine on neural responses to traumatic memories in a small sample of patients with PTSD, as measured with PET imaging; we hypothesized that paroxetine treatment would be associated with increased regional cerebral blood flow (rCBF) in the medial prefrontal cortex. Thirteen participants with PTSD were given controlled-release paroxetine (paroxetine CR) or placebo in a randomized, double-blind fashion for 12 weeks. Participants underwent brain imaging using positron emission tomography (PET) before and at the end of treatment in conjunction with exposure to neutral scripts and personalized trauma scripts. Participants treated with paroxetine CR and placebo both exhibited significantly increased rCBF in the ACC during trauma versus neutral script presentations; however, we noted an increase in function in the orbitofrontal cortex (OFC) in paroxetine-treated (but not placebo-treated) participants. Participants in both groups showed decreases in overall PTSD symptomatology following treatment; paroxetine-treated participants showed a slightly greater percentage decrease in symptoms. These preliminary findings indicate that increased ACC function represents a nonspecific response to treatment, whereas increased OFC function is specifically associated with paroxetine treatment in PTSD. These pilot data reveal putative mechanisms for SSRI treatment in PTSD and substantiate the need for large-scale placebo-controlled studies investigating these effects.