TY - JOUR
T1 - Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia
AU - Pries, Lotta-Katrin
AU - van Os, Jim
AU - ten Have, Margreet
AU - de Graaf, Ron
AU - van Dorsselaer, Saskia
AU - Bak, Maarten
AU - Lin, Bochao D.
AU - van Eijk, Kristel R.
AU - Kenis, Gunter
AU - Richards, Alexander
AU - O'Donovan, Michael C.
AU - Luykx, Jurjen J.
AU - Rutten, Bart P. F.
AU - Guloksuz, Sinan
N1 - Funding Information:
Netherlands Institute of Mental Health and Addiction (Trimbos Institute) in Utrecht, supported by the Ministry of Health, Welfare and Sport and the Netherlands Organization for Health Research and Development. The study was also supported by grant agreement HEALTH-F2-2009-241909 (Project EU-GEI) from the European Community’s Seventh Framework Program; program grant G08005009 and Centre grant MR/L010305/1 from the Medical Research Council (Dr O’Donovan); VIDI award 91718336 from the Netherlands Scientific Organisation (Dr Rutten); and ZonMw grant 636340001 from the Ophelia research project (Drs Guloksuz and van Os). Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
reported receiving grants from the European Union and Medical Research Council UK during the conduct of the study and a collaborative research grant from Takeda Pharmaceuticals outside the conduct of the study. No other disclosures were reported.
Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - This cohort study assesses whether recent stressful life events interact with genetic and environmental liability for schizophrenia in models of mental and physical health in the Dutch adult population.Key PointsQuestionIs the association of adulthood life stress with mental and physical health moderated by polygenic risk and exposome scores for schizophrenia? FindingsThis population-based cohort study of 6646 participants provides novel evidence of the associations of genetic and environmental liability for schizophrenia with mental health in the general population. Both genetic and environmental liability were associated with poor outcomes, particularly mental health, and the association between stressful life events and health outcomes was moderated by exposome score but not polygenic risk score for schizophrenia. MeaningThese findings showing an interaction between adulthood stressful life events and lifetime exposomic liability lend further support to the diathesis-stress model.ImportanceBoth adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction remains to be elucidated to improve population-based health outcomes. ObjectiveTo test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health. Design, Setting, and ParticipantsThe Netherlands Mental Health Survey and Incidence Study-2 is a population-based prospective cohort study designed to investigate the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population. Participants were enrolled from November 5, 2007, to July 31, 2009, and followed up with 3 assessments during 9 years. Follow-up was completed on June 19, 2018, and data were analyzed from September 1 to November 1, 2019. ExposuresRecent SLEs assessed at each wave and aggregate scores of genetic and environmental liability for schizophrenia: polygenic risk score for schizophrenia (PRS-SCZ) trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia (ES-SCZ) trained using an independent data set. Main Outcomes and MeasuresIndependent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients. ResultsOf the 6646 participants included at baseline, the mean (SD) age was 44.26 (12.54) years, and 3672 (55.25%) were female. The SLEs were associated with poorer physical health (B=-3.22 [95% CI, -3.66 to -2.79]) and mental health (B=-3.68 [95% CI, -4.05 to -3.32]). Genetic and environmental liability for schizophrenia was associated with poorer mental health (ES-SCZ: B=-3.07 [95% CI, -3.35 to -2.79]; PRS-SCZ: B=-0.93 [95% CI, -1.31 to -0.54]). Environmental liability was also associated with poorer physical health (B=-3.19 [95% CI, -3.56 to -2.82]). The interaction model showed that ES-SCZ moderated the association of SLEs with mental (B=-1.08 [95% CI, -1.47 to -0.69]) and physical health (B=-0.64 [95% CI, -1.11 to -0.17]), whereas PRS-SCZ did not. Several sensitivity analyses confirmed these results. Conclusions and RelevanceIn this study, schizophrenia liability was associated with broad mental health outcomes at the population level. Consistent with the diathesis-stress model, exposure to SLEs, particularly in individuals with high environmental liability for schizophrenia, was associated with poorer health. These findings underline the importance of modifiable environmental factors during the life span for population-based mental health outcomes.
AB - This cohort study assesses whether recent stressful life events interact with genetic and environmental liability for schizophrenia in models of mental and physical health in the Dutch adult population.Key PointsQuestionIs the association of adulthood life stress with mental and physical health moderated by polygenic risk and exposome scores for schizophrenia? FindingsThis population-based cohort study of 6646 participants provides novel evidence of the associations of genetic and environmental liability for schizophrenia with mental health in the general population. Both genetic and environmental liability were associated with poor outcomes, particularly mental health, and the association between stressful life events and health outcomes was moderated by exposome score but not polygenic risk score for schizophrenia. MeaningThese findings showing an interaction between adulthood stressful life events and lifetime exposomic liability lend further support to the diathesis-stress model.ImportanceBoth adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction remains to be elucidated to improve population-based health outcomes. ObjectiveTo test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health. Design, Setting, and ParticipantsThe Netherlands Mental Health Survey and Incidence Study-2 is a population-based prospective cohort study designed to investigate the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population. Participants were enrolled from November 5, 2007, to July 31, 2009, and followed up with 3 assessments during 9 years. Follow-up was completed on June 19, 2018, and data were analyzed from September 1 to November 1, 2019. ExposuresRecent SLEs assessed at each wave and aggregate scores of genetic and environmental liability for schizophrenia: polygenic risk score for schizophrenia (PRS-SCZ) trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia (ES-SCZ) trained using an independent data set. Main Outcomes and MeasuresIndependent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients. ResultsOf the 6646 participants included at baseline, the mean (SD) age was 44.26 (12.54) years, and 3672 (55.25%) were female. The SLEs were associated with poorer physical health (B=-3.22 [95% CI, -3.66 to -2.79]) and mental health (B=-3.68 [95% CI, -4.05 to -3.32]). Genetic and environmental liability for schizophrenia was associated with poorer mental health (ES-SCZ: B=-3.07 [95% CI, -3.35 to -2.79]; PRS-SCZ: B=-0.93 [95% CI, -1.31 to -0.54]). Environmental liability was also associated with poorer physical health (B=-3.19 [95% CI, -3.56 to -2.82]). The interaction model showed that ES-SCZ moderated the association of SLEs with mental (B=-1.08 [95% CI, -1.47 to -0.69]) and physical health (B=-0.64 [95% CI, -1.11 to -0.17]), whereas PRS-SCZ did not. Several sensitivity analyses confirmed these results. Conclusions and RelevanceIn this study, schizophrenia liability was associated with broad mental health outcomes at the population level. Consistent with the diathesis-stress model, exposure to SLEs, particularly in individuals with high environmental liability for schizophrenia, was associated with poorer health. These findings underline the importance of modifiable environmental factors during the life span for population-based mental health outcomes.
KW - DEPRESSIVE SYMPTOMS
KW - POLYGENIC RISK
KW - DISORDERS
KW - CHILDHOOD
KW - PSYCHOSIS
KW - ADVERSITY
KW - ANXIETY
KW - EXPERIENCES
KW - ADULTS
KW - ABUSE
U2 - 10.1001/jamapsychiatry.2020.2304
DO - 10.1001/jamapsychiatry.2020.2304
M3 - Article
C2 - 32805017
SN - 2168-622X
VL - 77
SP - 1296
EP - 1304
JO - JAMA Psychiatry
JF - JAMA Psychiatry
IS - 12
ER -