The intermediary role of adolescent temperamental and behavioral traits on the prospective associations between polygenic risk and cannabis use among young adults of European Ancestry.

BACKGROUND AND AIMS: Cannabis use (CU) is an etiologically complex behavior with several social, temperamental, neurocognitive, and behavioral precursors. Biometrical and molecular studies suggest an interplay of environmental and pleiotropic influences. However, it remains unclear whether identified genetic effects related to behavioral and temperamental characteristics have developmentally direct or indirect mechanisms on CU behavior. The Transmissible Liability Index (TLI) is a measure of continuous liability based on developmental precursors of substance use disorders. This study aimed to examine if the TLI plays a role in understanding genetic risk for CU behaviors. DESIGN: Genome-wide association studies (n > 10 000; European Ancestry [EA]) of CU, risk tolerance, neuroticism, anxiety, and depression were used to construct polygenic scores (PGSs). Analyses assessed whether PGSs indirectly impacted risk for repeated use via TLI. SETTING: United States of America. PARTICIPANTS: From Add Health study, 4077 individuals of EA age 11 to 21 during baseline interview collection. MEASUREMENTS: Outcomes were initiation and repeated cannabis use (>5× in lifetime). The TLI was parameterized using a latent factor from 21 questions assessing for precursors of disordered use. FINDINGS: The marker-based heritability of TLI, initiation, and repeated use were significant, but modest (14%, P = 0.033; 15%, P = 0.025; and 17%, P = 0.008, respectively). TLI and repeated use were genetically correlated (rg  = 0.76, P = 0.033). The PGS for CU was associated with increased risk for repeated use and PGS for risk tolerance and depression were associated with TLI. Mediation analyses indicated significant, but very weak, indirect effects of PGS for risk tolerance and depression on repeated CU via the TLI. CONCLUSIONS: Adolescent behavioral and temperamental characteristics (i.e. the Transmissible Liability Index) appear to be early indicators of repeated cannabis use in adulthood. Although polygenic scores for cannabis use directly increased risk for repeated cannabis use, weak evidence was found for the role of polygenic scores of other internalizing/externalizing traits acting through adolescent derived Transmissible Liability Index on cannabis use behavior.

Risk for alcohol use/misuse among entering college students: The role of personality and stress.

INTRODUCTION: Excessive alcohol use amongst college students is associated with low grades, poor mental health, and risks to physical safety. Neuroticism, characterized by emotional instability and anxiety, and self-reported stress have both been shown to be strong predictors of alcohol use and misuse, however, previous studies have shown that measures of stress and Neuroticism are frequently confounded. This study tests the hypothesis that personality traits, and Neuroticism in particular, predict alcohol use/misuse in matriculating freshmen above and beyond reported levels of stress. METHODS: Data were collected as part of an IRB-approved longitudinal study, MAPme, examining behavioral health in college. Participants were 303 first-year college students (70% female) with an average age of 18.58 (SD = 0.39). Data were collected during the first eight weeks of the first semester at college. RESULTS: Overall, domain-level Neuroticism was not associated with alcohol use/misuse above and beyond perceived levels of stress and other Big Five domains (ß = 0.14, p = 0.088). Notably, the depression facet of Neuroticism (Neuroticism-Depression), was positively associated with alcohol use/misuse when accounting for the shared effects of stress. Results demonstrated that the Neuroticism-Depression facet moderated the relationship between stress and alcohol use/misuse (ß = 0.18, p = 0.020). CONCLUSIONS: The Neuroticism-Depression facet is a better predictor of alcohol use/misuse than the Neuroticism domain, even when accounting for stress and other personality domains.At low levels of the Depression facet, stress was negatively associated with alcohol use/misuse, but at high levels of the Depression facet, stress was positively associated with alcohol use/misuse. Taken together, our results shed new light into the combined and independent effects of Neuroticism and stress on alcohol use/misuse.