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Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study.

ABSTRACT: OBJECTIVE:Experience of stressful life events is associated with risk of depression. Yet many exposed individuals do not become depressed. A controversial hypothesis is that genetic factors influence vulnerability to depression following stress. This hypothesis is often tested with a "diathesis-stress" model, in which genes confer excess vulnerability. The authors tested an alternative formulation of this model: genes may buffer against depressogenic effects of life stress. METHOD:The hypothesized genetic buffer was measured using a polygenic score derived from a published genome-wide association study of subjective well-being. The authors tested whether married older adults who had higher polygenic scores were less vulnerable to depressive symptoms following the death of their spouse compared with age-matched peers who had also lost their spouse and who had lower polygenic scores. Data were analyzed from 8,588 non-Hispanic white adults in the Health and Retirement Study (HRS), a population-representative longitudinal study of older adults in the United States. RESULTS:HRS adults with higher well-being polygenic scores experienced fewer depressive symptoms during follow-up. Those who survived the death of their spouses (N=1,647) experienced a sharp increase in depressive symptoms following the death and returned toward baseline over the following 2 years. Having a higher well-being polygenic score buffered against increased depressive symptoms following a spouse's death. CONCLUSIONS:The effects were small, and the clinical relevance is uncertain, although polygenic score analyses may provide clues to behavioral pathways that can serve as therapeutic targets. Future studies of gene-environment interplay in depression may benefit from focus on genetics discovered for putative protective factors.

SUBMITTER: Domingue BW

PROVIDER: S-EPMC5610918 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study.

Domingue Benjamin W BW Liu Hexuan H Okbay Aysu A Belsky Daniel W DW

The American journal of psychiatry 20170324 10

<h4>Objective</h4>Experience of stressful life events is associated with risk of depression. Yet many exposed individuals do not become depressed. A controversial hypothesis is that genetic factors influence vulnerability to depression following stress. This hypothesis is often tested with a "diathesis-stress" model, in which genes confer excess vulnerability. The authors tested an alternative formulation of this model: genes may buffer against depressogenic effects of life stress.<h4>Method</h4 ...[more]

PMID: 28335623

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Project description:AimsRetirement is a major life transition that may improve or worsen mental health, including depression. Existing studies provide contradictory results. We conducted a systematic review with meta-analysis to quantitatively pool available evidence on the association of retirement and depressive symptoms.MethodsWe applied PRISMA guidelines to conduct a systematic review and meta-analysis to retrieve, quantitatively pool and critically evaluate the association between retirement and both incident and prevalent depression and to understand better the potential role of individual and contextual-level determinants. Relevant original studies were identified by searching PubMed, Embase, PsycINFO and the Cochrane Library, through 4 March 2021. Subgroup and sensitivity meta-analyses were conducted by gender, study design (longitudinal v. cross-sectional studies), study quality score (QS) and considering studies using validated scales to diagnose depression. Heterogeneity between studies was evaluated with I2 statistics.ResultsForty-one original studies met our a priori defined inclusion criteria. Meta-analysis on more than half a million subjects (n = 557 111) from 60 datasets suggested a protective effect of retirement on the risk of depression [effect size (ES) = 0.83, 95% confidence interval (CI) = 0.74-0.93], although with high statistical heterogeneity between risk estimates (χ2 = 895.19, df = 59, I2 = 93.41%, p-value < 0.0001). Funnel plot asymmetry and trim and fill method suggested a minor potential publication bias. Results were consistent, confirm their robustness and suggest stronger protective effects when progressively restricting the included studies based on quality criteria: (i) studies with the highest QS [55 datasets, 407 086 subjects, ES = 0.81, 95% CI = 0.71-0.91], (ii) studies with a high QS and using validated assessment tools to diagnose depression (44 datasets, 239 453 subjects, ES = 0.76, 95% CI = 0.65-0.88) and (iii) studies of high quality, using a validated tool and with a longitudinal design (24 datasets, 162 004 subjects, ES = 0.76, 95% CI = 0.64-0.90). We observed a progressive reduction in funnel plot asymmetry. About gender, no statistically significant difference was found (females ES = 0.79, 95% CI = 0.61-1.02 v. men ES = 0.87, 95% CI = 0.68-1.11).ConclusionsPooled data suggested that retirement reduces by nearly 20% the risk of depression; such estimates got stronger when limiting the analysis to longitudinal and high-quality studies, even if results are affected by high heterogeneity.As retirement seems to have an independent and protective effect on mental health and depressive symptoms, greater flexibility in retirement timing should be granted to older workers to reduce their mental burden and avoid the development of severe depression. Retirement may also be identified as a target moment for preventive interventions, particularly primary and secondary prevention, to promote health and wellbeing in older ages, boosting the observed impact.

Dataset Information

Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study.

Publications

Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study.

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