Biopsychosocial exposure to the COVID-19 pandemic and the relative risk of schizophrenia: Interrupted time-series analysis of a nationally representative sample

BACKGROUND: Studies of COVID-19 pandemic biopsychosocial exposure and schizophrenia risk showed contradictory results, were undertaken early in the pandemic, and did not consider lockdowns or COVID-19 infection. Hence, we examined the association between COVID-19 biopsychosocial exposure and incident schizophrenia.

METHODS: An interrupted time-series study design was implemented based on Israeli electronic health records from 2013 to 2021 with national coverage. The period coinciding with the COVID-19 pandemic biopsychosocial exposures from March 2020 to February 2021 was classified as exposed, otherwise unexposed. The effect of the COVID-19 pandemic on incident schizophrenia was quantified by fitting a Poisson regression and modeling the relative risk (RR) and corresponding 95% confidence intervals (CI). Three scenarios were projected from the third lockdown to 10 months to forecast incident schizophrenia rates and their associated 95% prediction intervals (PI).

RESULTS: The total population (N = 736,356) yielded 4,310 cases of incident schizophrenia over time. The primary analysis showed that the period exposed to the COVID-19 pandemic was associated with a reduced RR (RR = 0.81, 95% CI = 0.73, 0.91, p < 0.001). This conclusion was supported in 12 sensitivity analyses, including scrutinizing lockdowns and COVID-19 infection status. Two of three forecast scenarios projected an incident increase (6.74, 95% PI = 5.80, 7.84; 7.40, 95% PI = 6.36, 8.60).

CONCLUSIONS: The reduced risk of schizophrenia during the pandemic suggests no immediate triggering of new onsets either by the virus or the pandemic-induced psychosocial adversities. Once restrictions are lifted, the increased projected presentations have implications for clinicians and healthcare policy.