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Original Research

Corticotropin-Releasing Factor, Interleukin-6, Brain-Derived Neurotrophic Factor, Insulin-Like Growth Factor-1, and Substance P in the Cerebrospinal Fluid of Civilians With Posttraumatic Stress Disorder Before and After Treatment With Paroxetine

Omer Bonne, MD; Jessica Mary Gill, RN, PhD; David A. Luckenbaugh, MS; Carlos Collins, MD; Michael J. Owens, MD; Salvadore Alesci, MD; Alexander Neumeister, MD; Peixiong Yuan, MD, PhD; Becky Kinkead, PhD; Huesseni K. Manji, MD; Dennis S. Charney, MD; and Meena Vythilingam, MD

Published: December 28, 2010

Article Abstract

Background: Posttraumatic stress disorder (PTSD) is associated with altered concentrations of stress-related neurohormones, neurotrophins, and neuropeptides in plasma and serum; however, few studies have examined central alterations of these measures in individuals with PTSD. Furthermore, no study to date has evaluated the effects of successful antidepressant treatment on cerebrospinal fluid (CSF) abnormalities in PTSD.

Method: Sixteen medication-free outpatients with chronic PTSD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) due to physical and/or sexual abuse or motor vehicle accidents (mean ± SD age = 36 ± 11.4 years, 12 women) and 11 nontraumatized healthy subjects (mean ± SD age = 35.3 ± 13.1 years, 7 women) underwent a lumbar puncture for collection of CSF. Seven PTSD patients had a repeat lumbar puncture 12 weeks later, after successful treatment of PTSD with paroxetine. CSF was analyzed for corticotropin-releasing factor (CRF), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and substance P concentrations. The study was conducted between January 2003 and August 2004.

Results: Compared to nontraumatized healthy controls, patients with chronic PTSD had similar pretreatment concentrations of CSF CRF, IL-6, BDNF, IGF-1, and substance P. Posttreatment CSF measures did not change significantly in patients whose symptoms remitted with paroxetine.

Conclusions: Chronic, moderate PTSD due to civilian trauma, without psychotic symptoms and without significant rates of comorbid depression, alcohol dependence, or substance dependence, is not associated with abnormalities in CSF CRF, IL-6, BDNF, IGF-1, or substance P levels. Despite substantial reduction in PTSD symptoms, antidepressant treatment does not alter normal central concentrations of these neurochemicals, with the possible exception of substance P.

J Clin Psychiatry 2011;72(8):1124-1128

Date submitted: February 5, 2009; accepted March 10, 2010.

Online ahead of print: December 28, 2010 (doi:10.4088/JCP.09m05106blu).

Corresponding author: Omer Bonne, MD, Department of Psychiatry, Hadassah Hebrew University Medical Center, POB 12000, Jerusalem, Israel 91120 (

Volume: 71

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