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Schizophrenia and the Environment: Within-Person Analyses May be Required to Yield Evidence of Unconfounded and Causal Association—The Example of Cannabis and Psychosis

J. van Os, L. Pries, M. Ten Have, R. de Graaf, S. van Dorsselaer, M. Bak, H. Wittchen, B. Rutten, S. Guloksuz

Schizophrenia bulletin March 8, 2021 DOI: 10.1093/schbul/sbab019 via Semantic Scholar

Summary

AI-generated from the abstract

Using a within-person design that controls for fixed genetic and nongenetic confounders, data from two general population cohorts followed over about 10 years show that prior cannabis use is strongly associated with later attenuated psychotic experiences (adjusted odds ratio 7.03). In contrast, prior psychotic experiences were not associated with later cannabis use. The findings suggest a causal effect of cannabis on psychosis, but not the reverse.

Study at a glance

Characteristics Prospective cohort with within-person fixed-effects analysis Longitudinal Peer reviewed
Sample size 7,998
Population General population from the Netherlands (Early Developmental Stages of Psychopathology Study and Netherlands Mental Health Survey and Incidence Study-2)
Duration Approximately 10 years
Keywords Medicine Psychology Environmental science
Key finding Prior cannabis use was associated with a sevenfold increase in the odds of later psychotic experiences, while prior psychotic experiences did not predict later cannabis use.

Abstract

Abstract Hypotheses about the link between cannabis use and psychosis apply to the within-person level but have been tested mostly at the between-person level. We used a within-person design, in which a person serves as his own control, thus removing the need to consider confounding by any fixed (genetic and nongenetic) characteristic to study the prospective association between cannabis use and the incidence of attenuated psychotic experiences, and vice versa, adjusted for time-varying confounders. We combined 2 general population cohorts (at baseline: Early Developmental Stages of Psychopathology Study, n = 1395; Netherlands Mental Health Survey and Incidence Study-2, n = 6603), which applied a similar methodology to study cannabis use and attenuated psychotic experiences with repeated interviews (T0, T1, T2, and T3) over a period of approximately 10 years. The Hausman test was significant for the adjusted models, indicating the validity of the fixed-effects model. In the adjusted fixed-effects model, prior cannabis use was associated with psychotic experiences (aOR = 7.03, 95% CI: 2.39, 20.69), whereas prior psychotic experiences were not associated with cannabis use (aOR = 0.59, 95% CI: 0.21, 1.71). Longitudinal studies applying random-effects models to study associations between risk factors and mental health outcomes, as well as reverse causality, may not yield precise estimates. Cannabis likely impacts causally on psychosis but not the other way round.

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