Low resilience to stress is associated with candidate gene expression alterations in the dopaminergic signalling pathway

Psychogeriatrics. 2018 May;18(3):190-201. doi: 10.1111/psyg.12312. Epub 2018 Feb 8.

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.

Keywords: COMT; DRD2; dopamine; biomarker; resilience; stress.

MeSH terms

  • Adolescent
  • Adult
  • Brain-Derived Neurotrophic Factor*
  • Catechol O-Methyltransferase
  • Dopamine Plasma Membrane Transport Proteins*
  • Down-Regulation
  • Gene Expression Regulation
  • Glial Cell Line-Derived Neurotrophic Factor*
  • Humans
  • Iran
  • Real-Time Polymerase Chain Reaction
  • Receptors, Dopamine / genetics*
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D2
  • Resilience, Psychological*
  • Serotonin*
  • Stress, Psychological / genetics*
  • Up-Regulation
  • Young Adult

Substances

  • Brain-Derived Neurotrophic Factor
  • DRD2 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Serotonin
  • COMT protein, human
  • Catechol O-Methyltransferase