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

Azad-Marzabadi, Esfandiar; Haghighatfard, Arvin; Mohammadi, Alireza

doi:10.1111/psyg.12312

Cited by 40 publications

(25 citation statements)

References 47 publications

(94 reference statements)

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“…On the one hand, dopamine has both positive and negative effects on cognition, exhibiting an inverted U-shaped dose-response curve (25). Gene expression changes in the dopaminergic signaling pathway are linked with the resilient/vulnerability profile, which is in agreement with our data (26). In addition, we also found a negative correlation between cerebellar Drd1 gene expression and walking adaptability performance in mice.…”

Section: Submission Files Included In This Pdfsupporting

confidence: 91%

Dual influences of early life stress induced by limited bedding on walking adaptability and Bdnf/TrkB and Drd1/Drd2 gene expression in different mouse brain regions

Wearick-Silva

Orso

Martins

et al. 2019

Behavioural Brain Research

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Introduction: Evidence suggests early life stress impairs development, quality of life and increases vulnerability to disease. One important aspect of the stress experience is its impact on cognitive-motor performance, which includes the ability to adapt walking according to the environmental conditions. This study aimed to investigate how early-life stress affects walking adaptability of mice, while investigating BDNF/TrkB and Drd1/Drd2 expression in different brain regions. Methods: Briefly, we exposed male C56BL/6 to the limited bedding protocol (LB) from post-natal day (PND) 2 to PND9 and then tested animals in the ladder walking task at PND60. RT-qPCR was used to investigate gene expression in the mPFC, hippocampus, motor cortex and cerebellum 2h after the task. Results: LB induced a wide range of variability and therefore two distinct subgroups of animals within the LB group were established: a) superior performance (LB-SP); and b) inferior performance (LB-IP), compared to controls. Additionally, Drd1 gene expression was increased in the mPFC of LB-IP animals and in the cerebellum of LB-SP animals, while Drd2 expression was reduced in the hippocampus of the LB-IP group. BDNF exon IV gene expression in the mPFC and motor cortex was increased in both the LB-IP and LB-SP subgroups. TrkB gene expression in the hippocampus was reduced in the LB-IP group. A strong negative correlation was found between walking adaptability performance and BDNF exon IV gene expression in the motor cortex. Conversely, a positive correlation was found between walking adaptability performance and TrkB expression in the mPFC and a negative correlation in the hippocampus. Both Drd1 and Drd2 gene expression were negatively correlated with the ability to adapt walking. Conclusions: Overall, our findings suggest exposure to early life stress leads to distinct walking adaptability phenotypes, which may be related to Drd1, Drd2, Bdnf exon IV and TrkB gene expression in brain regions that influence walking adaptability.

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Section: Submission Files Included In This Pdfsupporting

confidence: 91%

Dual influences of early life stress induced by limited bedding on walking adaptability and Bdnf/TrkB and Drd1/Drd2 gene expression in different mouse brain regions

Wearick-Silva

Orso

Martins

et al. 2019

Behavioural Brain Research

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“…Of the 51 selected studies, 50 studies examined the biological mechanisms of PTSD, and one study (Azadmarzabadi, Haghighatfard, & Mohammadi, ) investigated stress levels in response to PTEs but did not use a measure of PTSD symptomology. The results of these individual studies are summarized in Supplementary Tables 1–3.…”

Section: Resultsmentioning

confidence: 99%

“…Kohrt and colleagues (2016) assessed resilience in child soldiers using the Resilience Scale (Wagnild & Young, ) and found that a high level of resilience was significantly associated with down‐regulated cell cycle transcriptional regulator (CTRA) gene expression (i.e., immune gene). In contrast, Azadmarzabadi and colleagues () used the Connor‐Davidson Resilience Scale (Connor & Davidson, ) to measure resilience and assessed the association between gene expression and reduced stress resilience. Reduced stress resilience was significantly associated with overexpression in dopamine genes.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of DNA Methylation and Gene Expression Studies in Posttraumatic Stress Disorder, Posttraumatic Growth, and Resilience

Mehta

Miller

Bruenig

et al. 2020

Journal of Traumatic Stress

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Most people will experience a traumatic event within their lifetime. One commonly recognized response to trauma exposure is posttraumatic stress disorder (PTSD). The biological underpinnings of PTSD, including epigenetic mechanisms of DNA methylation and gene expression, have been studied intensively. However, psychological posttrauma responses vary widely and can include positive outcomes, such as posttraumatic growth (PTG) and, more commonly, resilience. The aim of this systematic review was to summarize the current DNA methylation and gene expression data with respect to three potential posttrauma responses: PTSD, PTG, and resilience. A literature search identified 486 studies, 51 of which were deemed eligible for inclusion (total N = 10,633). All included studies examined PTSD and consistently implicated DNA methylation and gene expression changes in hypothalamic-pituitary-adrenal axis and inflammatory genes. Ten studies acknowledged resilience as a posttrauma response, but only two studies examined epigenetics and gene expression using a scale to measure resilience. Low resilience was associated with gene expression patterns in immune and dopamine genes, and high resilience was associated with a blunted inflammatory response. No studies examined epigenetic or gene expression changes associated with PTG. These findings highlight a focus on pathogenic research, which has failed to adequately acknowledge and measure positive posttrauma outcomes of PTG and resilience. Future research should examine DNA methylation and gene expression changes associated with PTG and resilience in addition to PTSD in order to gain a more comprehensive picture of an individual's well-being following exposure to trauma.

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“…However, very little work has been done in human brain tissues to determine the mechanism by which such associations occur. We do know that upregulation of DRD1 , DRD3 , and DRD5 expression in blood, along with alterations in the expression of other dopaminergic signaling genes, has been associated with lower resilience to stressful events and other psychological parameters, including personality, depression, anxiety, and intelligence, in age, sex, and race-matched individuals [ 11 ]. We also know that increasing binding of D1 receptors has been associated with younger age in suicide [ 12 ], and DRD5 variants have been associated with age of onset in pediatric attention-deficit/hyperactivity disorder (ADHD) patients [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of Dopamine-Related Genes in Four Human Brain Regions

Stanfill

Cao

2020

Brain Sciences

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A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions.

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

Abstract: 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.

Cited by 40 publications

References 47 publications

Dual influences of early life stress induced by limited bedding on walking adaptability and Bdnf/TrkB and Drd1/Drd2 gene expression in different mouse brain regions

Dual influences of early life stress induced by limited bedding on walking adaptability and Bdnf/TrkB and Drd1/Drd2 gene expression in different mouse brain regions

A Systematic Review of DNA Methylation and Gene Expression Studies in Posttraumatic Stress Disorder, Posttraumatic Growth, and Resilience

Expression of Dopamine-Related Genes in Four Human Brain Regions

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