Nicotine use and psychoticism: A longitudinal co-twin control analysis

Nicotine use, particularly in adolescence, has been linked to increased psychosis risk in observational studies; however, the causal status of these associations remains unclear. We analyzed data from 3,836 twins from two longitudinal community samples with repeated nicotine use measures from adolescence into adulthood and a dimensional measure of psychosis proneness (psychoticism) in adulthood. We used individual-level mixed-effects models and co-twin control analyses that decompose associations into between-pair (familial) and within-pair (controlling for shared genetic and environmental factors) components, covarying sex, zygosity, cohort, age, and co-occurring substance use. Adolescent nicotine use predicted adult psychoticism at the individual level (β = .09, 95% confidence interval [CI; .06, .12]). Co-twin control analyses revealed significant between-pair effects (β = .10, 95% CI [.07, .14]) but nonsignificant within-pair effects (β = .04, 95% CI [-.02, .11]), suggesting familial confounding. Effects attenuated after accounting for adulthood nicotine use, suggesting longitudinal associations are attributable to continuity of nicotine exposure. Prospective co-twin control models over 4 years in adulthood also yielded null within-pair effects (β = .02, 95% CI [-.07, .11]). In contrast, cross-sectional adulthood associations persisted at the within-pair level (β = .12, 95% CI [.07, .17]), consistent with proximal rather than enduring effects. Taken together, associations between adolescent nicotine use and adulthood psychoticism appear largely attributable to shared familial factors and continuity of nicotine use into adulthood. Similarly, longitudinal analyses across two adult time points provide no evidence for enduring prospective causal effects. However, adult nicotine use shows cross-sectional associations with psychoticism, independent of familial confounding, suggesting potential causal effects over shorter term timescales warrant further investigation. (PsycInfo Database Record (c) 2026 APA, all rights reserved).