Blood gene expression profiles suggest altered immune function associated with symptoms of generalized anxiety disorder
Open accessAbstract
Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reverberations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 336 community participants (157 anxious and 179 control). We examined genome-wide differential gene expression in anxiety, as well as associations between nine major modules of co-regulated transcripts in blood gene expression and anxiety. No significant differential expression was observed in women, but 631 genes were differentially expressed between anxious and control men at the false discovery rate of 0.1 after controlling for age, body mass index, race, and batch effect. Gene set enrichment analysis (GSEA) revealed that genes with altered expression levels in anxious men were involved in response of various immune cells to vaccination and to acute viral and bacterial infection, and in a metabolic network affecting traits of metabolic syndrome. Further, we found one set of 260 co-regulated genes to be significantly associated with anxiety in men after controlling for the relevant covariates, and demonstrate its equivalence to a component of the stress-related conserved transcriptional response to adversity profile. Taken together, our results suggest potential molecular pathways that can explain negative effects of GAD observed in epidemiological studies. Remarkably, even mild anxiety, which most of our participants had, was associated with observable changes in immune-related gene expression levels. Our findings generate hypotheses and provide incremental insights into molecular mechanisms mediating negative physiological effects of GAD.
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Within a community sample of individuals with and without GAD, only males with GAD showed changes in immune-related gene expression compared with controls.
“Within a community sample of individuals with and without GAD, Wingo and Gibson (2015) found that only males with GAD showed changes in immune-related gene expression compared with controls (Wingo and Gibson, 2015).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Wingo and Gibson, 2015
The Abstract reports differential expression of 631 genes in anxious men but none significant in women, and links the altered genes to immune responses. However, Methods §2.2 defines the groups by GAD-7 symptom scores, not by confirmed GAD diagnoses; describing them as individuals with and without GAD overstates what was measured. (LLM, conf=0.88)
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Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond
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- Authors
- Wingo, A. P., & Gibson, G.
- Affiliations
- Emory University (US)
- Georgia Institute of Technology (US)
- Corresponding author
- Gibson, Greg
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 43
- Pages
- 184-191
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC4377320
- OpenAlex
- W2057239687
- Cited by
- 59
- References
- 45
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 3
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Brain Behavior and Immunity (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Department of Veterans Affairs Career Development Award (IK2CX000601)
- NARSAD Young Investigator Award (P01GM099568)
- Georgia Tech Research Institute
- Emory University School of Medicine
- NIH
- National Institutes of Health (UL1TR000454)
- NIGMS (P01 GM099568)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- generalized anxiety disorder, blood gene expression, immune function, sex differences, cardiovascular risk, metabolic syndrome, immune response to infection, stress response, mild anxiety
- MeSH terms
- Adult, Anxiety, Anxiety Disorders, Female, Humans, Immune System, Male, Middle Aged, Gene Expression Profiling, Transcriptome
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