An Analysis of Gene Expression in PTSD Implicates Genes Involved in the Glucocorticoid Receptor Pathway and Neural Responses to Stress

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Citation

Logue, Mark W.; Smith, Alicia K.; Baldwin, Clinton T.; Wolf, Erika J.; Guffanti, Guia; Ratanatharathorn, Andrew; Stone, Annjanette; Schichman, Steven A.; Humphries, Donald; & Binder, Elisabeth B., et al. (2015). An Analysis of Gene Expression in PTSD Implicates Genes Involved in the Glucocorticoid Receptor Pathway and Neural Responses to Stress. Psychoneuroendocrinology, 57, 1-13. PMCID: PMC4437870

Abstract

We examined the association between posttraumatic stress disorder (PTSD) and gene expression using whole blood samples from a cohort of trauma-exposed white non-Hispanic male veterans (115 cases and 28 controls). 10,264 probes of genes and gene transcripts were analyzed. We found 41 that were differentially expressed in PTSD cases versus controls (multiple-testing corrected p < 0.05). The most significant was DSCAM, a neurological gene expressed widely in the developing brain and in the amygdala and hippocampus of the adult brain. We then examined the 41 differentially expressed genes in a meta-analysis using two replication cohorts and found significant associations with PTSD for 7 of the 41 (p < 0.05), one of which (ATP6AP1L) survived multiple-testing correction. There was also broad evidence of overlap across the discovery and replication samples for the entire set of genes implicated in the discovery data based on the direction of effect and an enrichment of p < 0.05 significant probes beyond what would be expected under the null. Finally, we found that the set of differentially expressed genes from the discovery sample was enriched for genes responsive to glucocorticoid signaling with most showing reduced expression in PTSD cases compared to controls.

URL

http://dx.doi.org/10.1016/j.psyneuen.2015.03.016

Reference Type

Journal Article

Year Published

2015

Journal Title

Psychoneuroendocrinology

Author(s)

Logue, Mark W.
Smith, Alicia K.
Baldwin, Clinton T.
Wolf, Erika J.
Guffanti, Guia
Ratanatharathorn, Andrew
Stone, Annjanette
Schichman, Steven A.
Humphries, Donald
Binder, Elisabeth B.
Arloth, Janine
Menke, Andreas
Uddin, Monica
Wildman, Derek E.
Galea, Sandro
Aiello, Allison E.
Koenen, Karestan C.
Miller, Mark W.

PMCID

PMC4437870

ORCiD

Aiello - 0000-0001-7029-2537