The Neurobiology of Violence in a Psychosis Risk Cohort

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Cannabis exposure is an established environmental risk factor for the development of psychotic disorders, which are highly disabling conditions that carry major economic and societal costs. However, most marijuana users do not develop psychosis, and genetic factors appear to play a role in determining an individual's risk of cannabis-associated psychosis (CAP). Given the rapid advancement of psychiatric genetics, it is possible that personalized testing that could reveal an individual's level of genetic susceptibility to psychiatric conditions such as CAP could become available in the near future. The goal of providing the results of such testing to individuals would be to promote positive health behaviors (e.g., avoiding cannabis use if CAP susceptibility is elevated), but based on prior research is unclear whether such positive effects are likely to occur; it is also unclear how the effects of this kind of genetic testing might differ among individuals depending upon their history of cannabis use and their demographic characteristics. It is also possible that providing this kind of testing could have negative effects (e.g., promoting the belief among those who test negative for a predisposition to CAP that cannabis use is risk-free). Additionally, the notion of genetic susceptibility to CAP implies a gene-environment interaction—a concept that is notoriously difficult for laypeople to understand. This raises the possibility that information about CAP susceptibility could be fatalistically misinterpreted as implying that psychosis risk is determined by genetics alone, which could negatively impact feelings of self-efficacy regarding health behaviors. Questions about the potential for positive and negative effects of genetic testing for CAP susceptibility have important ethical and policy implications, especially given the ongoing push to legalize recreational marijuana use in various states throughout the US. The aims of the proposed supplement project are to (1) investigate, in a randomized experimental study of a nationally representative sample of individuals aged 18-30, the likely impact of personalized information about genetic CAP risk among those with and without a past history of marijuana use; (2) examine respondent demographic variables (e.g., race and ethnicity) as potential moderators of the effect of personalized genetic information; and (3) explore the potential for learning about one's genetic predisposition to CAP to be misunderstood as indicating susceptibility to psychosis even in the absence of cannabis use, due to genetic fatalism and failure to grasp the nature of gene-environment interactions, thereby decreasing feelings of health-related agency. Our results will be informative for the development of ethical standards and policy to guide the use of genetic testing for CAP susceptibility, including decision-making about whether to offer such testing and to whom. This will complement the parent R01 award, which focuses on better understanding violent ideation in individuals at risk for psychosis, as cannabis abuse in particular is one of the most substantial environmental risk factors for both psychosis and violence. This work will open up additional areas of study when examining links between violence and psychosis.