Low Resilience to Stress Is Associated with Candidate Gene Expression Alterations in the Dopaminergic Signalling Pathway
Abstract
BACKGROUND: In stressful situations, a person's ability to appropriately complete tasks with minimal anxiety is known as stress resilience. Genetic variants in neuropeptide Y, Corticotropin releasing hormone receptor 1 (CRHR1), and serotonin transporter have been previously reported to be associated with low resilience, but the relationship between low resilience and the dopaminergic signalling pathway is not well understood. Here, we aimed to describe the association between comprehensive psychological characteristics and messenger RNA levels of dopamine receptor D1 (DRD1), dopamine receptor D2 (DRD2), dopamine receptor D3 (DRD3), dopamine receptor D4 (DRD4), dopamine receptor D5 (DRD5), COMT, Dopamine Beta-Hydroxylase (DBH), Tyrosine hydroxylase (TH), monoamine oxidase A (MAOM), dopa decarboxylase (DDC), dopamine transporter (DAT), serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) genes based on peripheral blood samples from 400 subjects who react differently to major life event stressors. The blood samples were analyzed by quantitative real-time polymerase chain reaction. METHODS: Four hundred Iranian individuals (age range: 17-42 years) were selected from 18 of Iran's 31 provinces. They were divided into four groups: (i) group A, persons with normal reactions to major life-event stressors; (ii) group B, persons with acute stress reactions to major life-event stressors; (iii) group C, persons with normal reactions to crises/catastrophes; and (iv) group D, persons with acute stress reactions to crises/catastrophes. Individuals were divided into groups by a senior psychiatrist based on an unstructured interview, the 21-item Depression Anxiety Stress Scale, and Connor-Davidson Resilience Scale. RESULTS: We found that the upregulation of DRD1, DRD2, DRD3, DRD4, DBH, DAT, and BDNF and the downregulation of serotonin transporter, monoamine oxidase A, and COMT are associated with stress resilience, which is modulated by dopaminergic and serotonergic pathways. CONCLUSIONS: Gene expression variations were not only correlated with stress resilience, but they were also associated with other psychological parameters including personality, depression, anxiety, and intelligence.
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Mehta and colleagues' (2020) systematic review identified 51 studies, of which none examined PTG, and only two measured resilience.
“For example, Mehta and colleagues (2020) systematic review of DNA methylation and gene expression patterns associated with positive and negative posttrauma responses identified 51 studies, of which none examined PTG, and only two measured resilience (Azadmarzabadi et al., 2018;Kohrt et al., 2016).”
From DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. (2020) · cites this paper as Azadmarzabadi et al., 2018
Studies on law students found that genetic variability in the NPS/NPSR1 system becomes more evident under chronic stress conditions like exam preparation.
“Similarly, studies on law students found that genetic variability in the NPS/NPSR1 system becomes more evident under chronic stress conditions like exam preparation [17,22,41,109].”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [22]
Upregulation of DRD1-DRD4, DBH, DAT, and BDNF is associated with higher resilience.
“Variants in genes like NPY, CRHR1, and 5-HTT are linked to lower resilience, while upregulation of DRD1–DRD4, DBH, DAT, and BDNF is associated with higher resilience.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [22]
Research on medical students facing license examinations revealed significant changes in gene expression profiles in peripheral blood, validating changes in 10 key genes (DPYD, CSF3R, PLCB2, CTNNB1, PPP3CA, IRF3, POLM, CCNI, ARHGEF1, and TP53).
“Research on medical students facing license examinations revealed significant changes in gene expression profiles in peripheral blood, validating changes in 10 key genes (DPYD, CSF3R, PLCB2, CTNNB1, PPP3CA, IRF3, POLM, CCNI, ARHGEF1, and TP53).”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [22]
Stress resilience, the ability to manage anxiety under stress, is influenced by genetic factors.
“Stress resilience, the ability to manage anxiety under stress, is influenced by genetic factors.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [22]
Variants in genes like NPY, CRHR1, and 5-HTT are linked to lower resilience.
“Variants in genes like NPY, CRHR1, and 5-HTT are linked to lower resilience, while upregulation of DRD1–DRD4, DBH, DAT, and BDNF is associated with higher resilience.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [22]
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- Authors
- Azadmarzabadi, E., Haghighatfard, A., & Mohammadi, A.
- Affiliations
- Behavioral Sciences Research Center Baqiyatallah University of Medical Sciences Tehran Iran
- Islamic Azad University, Tehran (IR)
- Baqiyatallah University of Medical Sciences (IR)
- Corresponding author
- Mohammadi, Alireza
- Venue
- Psychogeriatrics
- Publisher
- Wiley
- Published
- 2018-02-08
- Volume
- 18
- Issue
- 3
- Pages
- 190-201
- ISSN
- 1346-3500 (ISSN-L)
- 1479-8301
- OpenAlex
- W2790007489
- Cited by
- 46
- References
- 49
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 13 · 2021: 8 · 2020: 8 · 2019: 4 · 2018: 1
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychogeriatrics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Baqiyatallah University of Medical Sciences (BMSU‐950840)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Resilience and Mental Health
- Keywords
- stress resilience, gene expression, dopamine receptors, serotonin transporter, brain-derived neurotrophic factor, catechol-O-methyltransferase, monoamine oxidase A, dopamine transporter, acute stress response, depression, anxiety, personality, intelligence, peripheral blood gene expression
- MeSH terms
- Adolescent, Adult, Catechol O-Methyltransferase, Gene Expression Regulation, Humans, Iran, Receptors, Dopamine, Serotonin, Stress, Psychological, Down-Regulation, Up-Regulation, Receptors, Dopamine D2, Brain-Derived Neurotrophic Factor, Dopamine Plasma Membrane Transport Proteins, Glial Cell Line-Derived Neurotrophic Factor, Resilience, Psychological, Young Adult, Real-Time Polymerase Chain Reaction
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