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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

Jim van Os, L. Pries, M. Ten Have, RON DE Graaf, S. van Dorsselaer, M. Bak, H. Wittchen, Bart P. F. Rutten, S. Guloksuz

Schizophrenia Bulletin March 8, 2021 DOI: 10.1093/schbul/sbab019 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
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
Topics Cannabis
Key findings 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.

Comparable studies

Other observational and cohort studies on cannabis, most cited first.

Study Year Design Participants
High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population 2009 Case-control study n = 454
Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population 2013 Observational study
Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people 2000 Observational
Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline 2011 Observational cohort n = 1,923
Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... 2005 Observational cohort n = 535

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