The conserved transcriptional response to adversity
Open accessAbstract
Gene expression profiling studies of people exposed to chronic threat have identified a Conserved Transcriptional Response to Adversity (CTRA) in circulating immune cells. This physiological pattern is characterized by up-regulated expression of genes involved in inflammation and down-regulated expression of genes involved in Type I interferon responses. The CTRA is mediated by beta-adrenergic signaling pathways that transduce sympathetic nervous system activity into changes in transcription factor activity and hematopoietic output of myeloid lineage immune cells (monocytes, neutrophils, and dendritic cells). Recent research has begun to identify the CNS processes that regulate peripheral CTRA activity, define its implications for disease, and explore the role of positive psychosocial factors in buffering such effects. The CTRA provides a genomic framework for understanding PNI relationships and connecting macro-level psychosocial processes to the micro-level biology of health and disease.
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The CTRA transcriptomic pattern is defined by relative upregulation of 19 inflammatory genes and relative downregulation of 31 type-1 interferon response genes and three antibody synthesis genes.
“Specifically, the CTRA transcriptomic pattern can be defined by relative upregulation of 19 inflammatory genes, and relative downregulation of 31 type-1 interferon response genes and three antibody synthesis genes [21,95] as displayed in Supplementary Table 5.”
From Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease (2025) · cites this paper as [21]
The Introduction supports the broad pattern of increased inflammatory-gene expression and decreased type I interferon-gene expression. But the Measurement section explicitly says the CTRA is not defined by the 53-gene contrast; it is one way to measure the pattern. The paper does not give the claimed 19/31/3 breakdown. (LLM, conf=0.86)
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Experimental — accuracy not yet measuredThe conserved transcriptional response to adversity (CTRA) is a 53-gene composite linked to chronic stress.
“It will examine expression of the conserved transcriptional response to adversity (CTRA), a 53-gene composite associated with chronic stress, as well as involvement of lymphocyte subsets [24].”
From Living Well: Protocol for a web-based program to improve quality of life in rural and urban ovarian cancer survivors (2024) · cites this paper as [24]
The Introduction links the CTRA pattern to chronic stress. The Measurement section says the 53-gene contrast is one way to measure CTRA, not the definition of CTRA itself, so calling CTRA a 53-gene composite overstates the source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe CTRA has been proposed as a potential predictive biomarker for disease risk and pathogenesis related to inflammatory and interferon response alterations, and may have utility as an indicator of AD progression.
“The CTRA has been proposed as a potential predictive biomarker for disease risk and pathogenesis related to diseases impacted by inflammatory and interferon response alterations including cancer and heart disease [96], and may have utility as an indicator of AD progression [21].”
From Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease (2025) · cites this paper as [21]
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“We measured transcriptomic changes in a chronic stress-related gene pro fi le termed the conserved transcriptional response to adversity (CTRA) [21] in peripheral blood mononuclear cells (PBMCs).”
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- Authors
- Cole, S. W.
- Venue
- Current Opinion in Behavioral Sciences
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 28
- Pages
- 31-37
- ISSN
- 2352-1546 (ISSN-L)
- PMC
- PMC6779418
- OpenAlex
- W2915157760
- Cited by
- 294
- References
- 42
- Citations by year
- 2026: 53 · 2025: 51 · 2024: 44 · 2023: 49 · 2022: 44 · 2021: 27 · 2020: 22 · 2019: 4
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Behavioral Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01-AG033590, P30-AG017265, R01-AG043404)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- conserved transcriptional response to adversity, gene expression profiling, circulating immune cells, inflammation, type I interferon response, beta-adrenergic signaling, sympathetic nervous system, monocytes, neutrophils, dendritic cells, central nervous system regulation, psychosocial factors, positive emotions, psychoneuroimmunology, adversity
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