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. 2025 Sep 8;51(5):1417-1427.
doi: 10.1093/schbul/sbae164.

Risk Factors for Late-Onset Psychosis: A Case-Control Study

Joseph P Skinner  1   2 , Ann K Shinn  1   3 , Lauren V Moran  1   2   3
Affiliations

Risk Factors for Late-Onset Psychosis: A Case-Control Study

Joseph P Skinner et al. Schizophr Bull. .

Abstract

Background and hypothesis: The onset of schizophrenia occurs after the age of 40 in up to 20% of cases. We aim to depict risk factors for first-episode psychosis after the age of 40 by comparing late-onset psychosis (LOP) patients to healthy age-matched controls.

Study design: In this case-control study using electronic health records, 142 individuals aged 40-65 years with an encounter for a first episode of psychosis between 2013 and 2021 were included. Four controls (N = 568) were matched to each case on age, sex, race, and year of encounter. Potential risk factors for the primary analysis were captured via structured data and text-mining of medical notes. Conditional logistic regression models were used to assess the odds of LOP with potential risk factors.

Study results: After adjusting for all variables in the main analysis, odds for LOP were increased by immigration (OR 3.30, 95% CI, 1.56-6.98), depression (OR 3.58, 95% CI, 2.01-6.38), anxiety (OR 2.12, 95% CI, 1.20-3.75), cannabis use (OR 3.00, 95% CI, 1.36-6.61), alcohol use disorder (OR 5.46, 95% CI, 2.41-12.36), polysubstance use (OR 4.22, 95% CI, 1.30-13.7), severe trauma (OR 2.29, 95% CI, 1.08-4.48), and caregiver burden (OR 15.26, 95% CI, 3.85-60.48).

Conclusions: Life stressors along with the effects of substance use and other psychiatric conditions may confer some risk to the development of LOP. Replication is required in independent prospective studies. Further research is necessary to truly parse out which of these factors belong on the causal pathway.

Keywords: cannabis; psychosocial; schizophrenia; substance use.

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Conflict of interest statement

Dr. Moran is an employee of Sage Therapeutics (start date after manuscript was written and edited), unrelated to the subject of this study. All other authors have declared that there are no conflicts of interest in relation to the subject of this study.

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