title: Glucocorticoid-related predictors and correlates of post-traumatic stress disorder treatment response in combat veterans.
abstract: The identification of biomarkers for post-traumatic stress disorder (PTSD) and resilience/recovery is critical for advancing knowledge about pathophysiology and treatment in trauma-exposed persons. This study examined a series of glucocorticoid-related biomarkers prior to and in response to psychotherapy. Fifty-two male and female veterans with PTSD were randomized 2 : 1 to receive either prolonged exposure (PE) therapy or a weekly minimal attention (MA) intervention for 12 consecutive weeks. Psychological and biological assessments were obtained prior to and following treatment and after a 12-week naturalistic follow-up. Response was defined dichotomously as no longer meeting criteria for PTSD at post-treatment based on the Clinician Administered PTSD Scale for DSM-IV (CAPS). Clinical improvement on the CAPS was apparent for both PE and MA, with no significant difference according to treatment condition. Biomarkers predictive of treatment gains included the BCLI polymorphism of the glucocorticoid receptor gene. Additional predictors of treatment response were higher bedtime salivary cortisol and 24 h urinary cortisol excretion. Pre-treatment plasma dehydroepiandrosterone/cortisol ratio and neuropetide Y (NPY) levels were predictors of reductions in PTSD symptoms, and, for NPY only, of other secondary outcomes as well, including anxiety and depression ratings. Glucocorticoid sensitivity changed in association with symptom change, reflecting clinical state. It is possible to distinguish prognostic and state biomarkers of PTSD using a longitudinal approach in the context of treatment. Identified markers may also be relevant to understanding mechanisms of action of symptom reduction.
authors.affiliation: James J. Peters Veterans Affairs Medical Center, New York, NY , USA ; Department of Psychiatry and Neuroscience , Icahn School of Medicine at Mount Sinai , New York, NY , USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yehuda
authors.affiliation: James J. Peters Veterans Affairs Medical Center, New York, NY , USA ; Department of Psychiatry and Neuroscience , Icahn School of Medicine at Mount Sinai , New York, NY , USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Pratchett
authors.affiliation: Department of Biochemistry and Cell Biology , Stony Brook University , Stony Brook , NY, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Elmes
authors.affiliation: James J. Peters Veterans Affairs Medical Center, New York, NY , USA ; Department of Psychiatry and Neuroscience , Icahn School of Medicine at Mount Sinai , New York, NY , USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Lehrner
authors.affiliation: James J. Peters Veterans Affairs Medical Center, New York, NY , USA ; Department of Psychiatry and Neuroscience , Icahn School of Medicine at Mount Sinai , New York, NY , USA.
authors.forename: Nikolaos P
authors.initials: NP
authors.lastname: Daskalakis
authors.affiliation: James J. Peters Veterans Affairs Medical Center, New York, NY , USA ; Department of Psychiatry and Neuroscience , Icahn School of Medicine at Mount Sinai , New York, NY , USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Koch
authors.affiliation: James J. Peters Veterans Affairs Medical Center, New York, NY , USA ; Department of Psychiatry and Neuroscience , Icahn School of Medicine at Mount Sinai , New York, NY , USA.
authors.forename: Iouri
authors.initials: I
authors.lastname: Makotkine
authors.affiliation: James J. Peters Veterans Affairs Medical Center, New York, NY , USA ; Department of Psychiatry and Neuroscience , Icahn School of Medicine at Mount Sinai , New York, NY , USA.
authors.forename: Janine D
authors.initials: JD
authors.lastname: Flory
authors.affiliation: James J. Peters Veterans Affairs Medical Center, New York, NY , USA ; Department of Psychiatry and Neuroscience , Icahn School of Medicine at Mount Sinai , New York, NY , USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bierer
keywords: biomarkers; glucocorticoid receptor; hypothalamic pituitary adrenal axis; neuropetide Y; post-traumatic stress disorder; psychotherapy