[Skip to Navigation]
Original Investigation
August 12, 2020

Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia

Author Affiliations
  • 1Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands
  • 2Department of Psychiatry, UMC (University Medical Center) Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
  • 3Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
  • 4Department of Epidemiology, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands
  • 5Flexible Assertive Community Treatment, Mondriaan Mental Health, Maastricht, the Netherlands
  • 6Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
  • 7Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands
  • 8MRC (Medical Research Council) Center for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom
  • 9GGNet Mental Health, Apeldoorn, the Netherlands
  • 10Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
JAMA Psychiatry. 2020;77(12):1296-1304. doi:10.1001/jamapsychiatry.2020.2304
Key Points

Question  Is the association of adulthood life stress with mental and physical health moderated by polygenic risk and exposome scores for schizophrenia?

Findings  This 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.

Meaning  These findings showing an interaction between adulthood stressful life events and lifetime exposomic liability lend further support to the diathesis-stress model.


Importance  Both 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.

Objective  To test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health.

Design, Setting, and Participants  The 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.

Exposures  Recent 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 Measures  Independent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients.

Results  Of 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 Relevance  In 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.

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words