Association of recent stressful life events with mental and physical health in the context of genomic and exposomic liability for schizophrenia

1. Environmental liability for schizophrenia moderated the association of stressful life events with mental and physical health.

Evidence Rating Level: 2 (Good)

Schizophrenia research has elucidated the roles of environmental and genetic liability as well as stressful life events (SLEs) in schizophrenia pathogenesis. However, few studies have illustrated the interactions of these risk factors and how they impact mental and physical health. This population-based prospective cohort study investigated the prevalence, incidence, course, and consequences of psychiatric disorders in the Netherlands. A total of 6,646 (M [SD] age = 44.26 [12.54] years, 55.25% female) participants were enrolled between November 5, 2007 and July 31, 2009, being followed up with by three assessments across nine years. Follow-ups included recent SLEs and aggregate scores of environmental and genetic liabilities (polygenic risk score for schizophrenia [PRS-SCZ]; exposome score for schizophrenia [ES-SCZ]). SLEs were significantly associated with reduced mental (B = -3.68, 95% CI -4.05 to -3.32) and physical health (B = -3.22, 95% CI -3.66 to -2.79). Genetic and environmental liabilities were associated with poorer mental health (PRS-SCZ: B = -0.93, 95% CI -1.31 to -0.54; ES-SCZ: B = -3.07, 95% CI -3.35 to -2.79), with environmental liability also being associated with reduced physical health (B = -3.19, 95% CI -3.56 to -2.82). The interaction model suggested that ES-SCZ moderated the association of SLEs with physical (B = -0.64, 95% CI -1.11 to -0.17) and mental health (B = -1.08, 95% CI -1.47 to -0.69). PRS-SCZ, however, did not moderate this relationship. Overall, both genetic and environmental liabilities for schizophrenia resulted in mental health outcomes across the population. Exposure to SLEs, specifically in the context of these liabilities, were further associated with poorer health outcomes. Thus, it is important to consider the environmental factors impacting schizophrenia, such that modifiable risk factors should be targets of prevention and ongoing treatment.

Click to read the study in JAMA Psychiatry

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