No abstract

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

Our results show that cannabis use was only predictive of transition to psychosis in those who met criteria for cannabis abuse or dependence, tentatively suggesting a dose-response relationship between current cannabis use and transition to psychosis.

Background . This study aims to evaluate the long-term costeffectiveness of add-on cognitive behavior therapy (CBT) for the prevention of psychosis for individuals at ultrahigh risk (UHR) of psychosis. Method. The Dutch Early Detection and Intervention randomized controlled trial was used, comparing routine care (RC; n = 101) with routine care plus CBT for UHR (here called CBTuhr; n = 95). A cost-effectiveness analysis was conducted with treatment response (defined as proportion of averted transitions to psychosis) as an outcome and a cost-utility analysis with quality-adjusted life years (QALYs) gained as a secondary outcome. Results. The proportion of averted transitions to psychosis was significantly higher in the CBTuhr condition (with a risk difference of 0.122; b = 1.324, SE b = 0.017, z = 7.99, P < 0.001). CBTuhr showed an 83% probability of being more effective and less costly than RC by −US$ 5777 (savings) per participant. In addition, over the 4-year follow-up period, cumulative QALY health gains were marginally (but not significantly) higher in CBTuhr than for RC (2.63 vs. 2.46) and the CBTuhr intervention had a 75% probability of being the superior treatment (more QALY gains at lower costs) and a 92% probability of being costeffective compared with RC at the Dutch threshold value (US$ 24 560; €20 000 per QALY). Conclusions. Add-on preventive CBTuhr had a high likelihood (83%) of resulting in more averted transitions to psychosis and lower costs as compared with RC. In addition, the intervention had a high likelihood (75%) of resulting in more QALY gains and lower costs as compared to RC.