Stressful Life Events Could Play a Role in the Development of Schizophrenia


Genetic and environmental liability were linked to poorer mental health in a cohort of more than 6000 individuals based in the Netherlands.

schizophrenia, depression, tragedy

A traumatic or stressful life event could ultimately lead to a schizophrenia diagnosis, according to new research.

A team, led by Lotta-Katrin Pries, MSc, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, examined whether recent stressful life events interact with genetic and environmental liability for schizophrenia in models of mental and physical health.

Stressful life events and liability for schizophrenia are both linked to poor mental and physical health in the general population. However, their interaction has not been elucidated to improve population-based health outcomes for these patients.

In the population-based prospective cohort, dubbed the Netherlands Mental Health Survey-2, the researchers investigated the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population.

Each patient was followed up with during 3 assessments over the course of 9 years.

The investigators assessed recent stressful life events at each wave and aggregated scores of genetic and environmental liability for schizophrenia. The polygenetic risk score for schizophrenia was trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia was trained using an independent data set.

The investigators sought main outcomes of independent and interacting associations of stressful life events with exposome score for schizophrenia (ES-SCZ) and polygenic risk score for schizophrenia (PRS-SCZ) on mental and physical health assessed at each wave using regression coefficients.

There were a total of 6646 patients included at baseline, with a mean age of 44.26 years old.

Overall, stressful life events were linked 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).

In addition, genetic and environmental liability were linked to 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), while environmental liability was linked to poorer physical health (B = −3.19; 95% CI, −3.56 to −2.82).

Using the interaction model, the investigators found ES-SCZ moderated the association of stressful life events 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).

However, PRS-SCZ did not moderate the association of stressful life events with mental and physical health.

The investigators confirmed the results using several sensitivity analyses.

“In this study, schizophrenia liability was associated with broad mental health outcomes at the population level,” the authors wrote. “Consistent with the diathesis-stress model, exposure to [stressful life events], 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.”

Approximately 30-40% of the general population experience at least 1 major stressful life event annually, suggesting that this could contribute to the onset and outcome of a broad range of mental disorders.

The study, “Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia,” was published online in JAMA Psychiatry.

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