An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress

Logue, Mark W.; Smith, Alicia K.; Baldwin, Clinton; 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; Galea, Sandro; Aiello, Allison E.; Koenen, Karestan C.; Miller, Mark W.

doi:10.1016/j.psyneuen.2015.03.016

Cited by 80Posttraumatic Stress Disorder ResearchStress Responses and CortisolChild Abuse and Trauma

An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress

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Logue, Mark W., Smith, Alicia K., Baldwin, Clinton, Wolf, Erika J., Guffanti, Guia, Ratanatharathorn, Andrew, Stone, Annjanette, Schichman, Steven A. +10 more·2015·Psychoneuroendocrinology

DOI 10.1016/j.psyneuen.2015.03.016PMC PMC4437870

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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.

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GR signaling is regulated at transcriptional and epigenetic levels and is dysregulated in HPA-axis-associated disorders.
“GR signaling is regulated at transcriptional and epigenetic levels and is dysregulated in HPA-axis-associated disorders (47).”
From Mechanistic inferences on metabolic dysfunction in posttraumatic stress disorder from an integrated model and multiomic analysis: role of glucocorticoid receptor sensitivity (2019) · cites this paper as [47]
The Results (3.3) report lower expression of the GR gene NR3C1 in PTSD cases, and the Discussion links GR signaling abnormalities to PTSD and possible HPA-axis dysregulation. The Discussion suggests a possible role for epigenetic mechanisms in the PTSD expression signature, but does not establish epigenetic regulation of GR signaling or extend its finding to HPA-axis-associated disorders generally. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Expression of the gene for thioredoxin (TXNRD1) is elevated in subjects with PTSD compared with traumatized controls.
“Finally, the expression of the gene for thioredexin (TXNRD1), a protein critical for responding to oxidative stress, is elevated in subjects with PTSD compared with traumatized controls (Logue et al, 2015).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Logue et al, 2015

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Authors: Logue, M. W., Smith, A. K., Baldwin, C., Wolf, E. J., Guffanti, G., Ratanatharathorn, A., Stone, A., Schichman, S. A., Humphries, D., Binder, E. B., Arloth, J., Menke, A., Uddin, M., Wildman, D., Galea, S., Aiello, A. E., Koenen, K. C., & Miller, M. W.
Affiliations: Boston University (US)
Emory University (US)
New York State Psychiatric Institute (US)
Columbia University (US)
Central Arkansas Veterans Healthcare System (US)
VA Boston Healthcare System (US)
Max Planck Society (DE)
Max Planck Institute of Psychiatry (DE)
University of Illinois Urbana-Champaign (US)
University of North Carolina at Chapel Hill (US)
Corresponding author: Logue, Mark W.
ORCID: Logue, Mark W.
Smith, Alicia K.
Wolf, Erika J.
Ratanatharathorn, Andrew
Stone, Annjanette
Schichman, Steven A.
Binder, Elisabeth B.
Arloth, Janine
Menke, Andreas
Uddin, Monica
Wildman, Derek
Galea, Sandro
Aiello, Allison E.
Koenen, Karestan C.
Miller, Mark W.
Venue: Psychoneuroendocrinology
Publisher: Elsevier BV
Published: 2015-07
Volume: 57
Pages: 1-13
ISSN: 0306-4530 (ISSN-L)
DOI: 10.1016/j.psyneuen.2015.03.016
PMC: PMC4437870
OpenAlex: W2012825983
Semantic Scholar: 15da96d4edb53ac8c3f24d8b340939f17214fa1b
Cited by: 80
References: 57
Citations by year: 2026: 3 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 11 · 2020: 11 · 2019: 9 · 2018: 11 · 2017: 10 · 2016: 6 · 2015: 4
FWCI: 12.83
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Psychoneuroendocrinology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
UNC Libraries
Funders: U.S. Department of Veterans Affairs VA CSR&D (R21MH102834)
BLR&D
NIH
United States (U.S.) Department of Veterans Affairs
Topics: Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Keywords: post-traumatic stress disorder, gene expression, glucocorticoid signaling, stress response, Dscam, veterans, trauma exposure, amygdala, hippocampus, differentially expressed genes, meta-analysis
MeSH terms: Adult, Amygdala, Brain, Humans, Male, Receptors, Glucocorticoid, Stress, Physiological, Stress Disorders, Post-Traumatic, United States, Veterans, Case-Control Studies, Polymorphism, Single Nucleotide, Transcriptome

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An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress

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