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Optimism and the conserved transcriptional response to adversity.

ABSTRACT: Dispositional optimism, a personality trait predisposing individuals to positive expectations, has been suggested to promote better health. However, little is known about the biological mechanism of the salubrious health effects of optimism. We hypothesized that by diminishing a sense of threat to the self, optimism will be associated with a healthier profile of gene expression in immune cells. Specifically, the "conserved transcriptional response to adversity" (CTRA) is activated by fight-or-flight stress responses and results in increased transcription of genes involved in inflammation and decreased transcription of genes involved in antiviral defense. In a sample of 114 male Japanese workers, we found that optimism was inversely linked to CTRA after controlling for demographic variables, health-risk factors, and indices of well-being. These results are consistent with the hypothesis that reduced activity of threat-related gene expression programs may contribute to the health effects associated with optimism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

SUBMITTER: Uchida Y

PROVIDER: S-EPMC6188811 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Optimism and the conserved transcriptional response to adversity.

Uchida Yukiko Y Kitayama Shinobu S Akutsu Satoshi S Park Jiyoung J Cole Steve W SW

Health psychology : official journal of the Division of Health Psychology, American Psychological Association 20180917 11

Dispositional optimism, a personality trait predisposing individuals to positive expectations, has been suggested to promote better health. However, little is known about the biological mechanism of the salubrious health effects of optimism. We hypothesized that by diminishing a sense of threat to the self, optimism will be associated with a healthier profile of gene expression in immune cells. Specifically, the "conserved transcriptional response to adversity" (CTRA) is activated by fight-or-fl ...[more]

PMID: 30221968

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Project description:Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum - Short Form. Analyses of a 2- representation of eudaimonia converged in finding correlated psychological and social subdomains of eudaimonic well-being to be the primary carriers of CTRA associations. Hedonic well-being showed no consistent CTRA association independent of eudaimonic well-being, and summary measures integrating hedonic and eudaimonic well-being showed less stable CTRA associations than did focal measures of eudaimonia (psychological and social well-being). Similar results emerged from analyses of pooled discovery and confirmation samples (n = 198). Similar results also emerged from analyses of a second new generalization study of 107 healthy adults that included the more detailed Ryff Scales of Psychological Well-being and found this more robust measure of eudaimonic well-being to also associate with reduced CTRA gene expression. Five of the 6 major sub-domains of psychological well-being predicted reduced CTRA gene expression when analyzed separately, and 3 remained distinctively prognostic in mutually adjusted analyses. All associations were independent of demographic characteristics, health-related confounders, and RNA indicators of leukocyte subset distribution. These results identify specific sub-dimensions of eudaimonic well-being as promising targets for future interventions to mitigate CTRA gene expression, and provide no support for any independent favorable contribution from hedonic well-being.

Project description:Self-rated health (SRH) is considered a strong indicator of well-being and clinical health status and has been linked to inflammatory markers. The objective of this work was to examine how self-rated physical health (SRPH) and mental health (SRMH) influence the immune system through the regulation of a stress-related gene expression profile known as the 'conserved transcriptional response to adversity' (CTRA), which involves the up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I interferon (IFN) response and antibody synthesis. CTRA expression data were derived from genome-wide transcriptional data on purified monocytes in 1264 adult participants from the multi-ethnic study of atherosclerosis. SRPH and SRMH were assessed through the SF-12 questionnaire. Multiple linear regression models were used to determine the association between the composite score of the CTRA subsets and SRPH and SRMH. Higher scores of SRPH and SRMH were associated with an increased expression of the overall CTRA profile. The individual gene subsets analysis did not reveal an increased expression of pro-inflammatory genes in persons with lower scores of SRH. However, we observed that higher scores of SRPH positively modulate the immune response through the up-regulation of both type I interferon response and antibody synthesis-related genes, while better scores of SRMH were associated with a down-regulation of genes involved in antibody synthesis. The significant association between SRH and a gene expression profile related to type I IFN response and antibody synthesis suggests that SRH may be linked to the immunocompetence status. Impact statement In this work, we evaluated for the first time how self-rated mental (SRMH) and physical health (SRPH) influence the immune response at the molecular level in a large multi-ethnic cohort. We observed that both SRMH and SRPH are related to immunocompetence status. These findings indicated that the link between how we perceive our health and poorer health outcomes could be explained by alterations in the immune response by shifting the expression of genes related to the type I IFN response and antibody synthesis.

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Optimism and the conserved transcriptional response to adversity.

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Optimism and the conserved transcriptional response to adversity.

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