Adolescents at the crossroads: genetic associations between psychotic symptoms and antisocial traits

<title>Abstract</title> Antisocial behaviour in youth has serious consequences at individual and societal level. Adolescence is also a critical period for the emergence of prodromal psychosis symptoms. Their co-occurrence may aggravate aggression and lead to severe adverse outcomes. Common genetic risk for psychosis, antisocial behaviour, and substance use has been suggested, but the putatively shared genetic architecture is unknown, and evidence in youth is limited. Here we examined whether common genetic liability indexed by polygenic risk scores (PRSs) relates to these complex traits in the Norwegian Mother, Father and Child Cohort Study (MoBa; n=18960). Antisocial behaviour was operationalised as three complementary dimensions: conduct-disorder (CD) traits, oppositional-defiant disorder (ODD) traits, and psychopathy traits. We first quantified phenotypic correlations between PLEs and the antisocial dimensions. We then evaluated PRS-phenotype associations (single-PRS and joint multivariable models) using PRSs for antisocial behaviour (PRSASB) and schizophrenia (PRSSCZ), in addition to PRS for alcohol use disorder (PRSAUD). We found phenotypic correlation between antisocial traits and PLEs (rs=0.13-0.34, p&lt;0.0001). This overlap was reflected on the genetic level, as we found associations between PRSASB and PLEs (p=0.0004). The associations between PRSSCZ and antisocial traits were present for CD (p=0.005) and ODD (p=0.003) traits. Both PLEs and antisocial traits were associated with PRSAUD. Patterns persisted in mutually adjusted models. These findings indicate cross-trait associations between polygenic liability for SCZ, ASB, AUD and adolescent PLEs and antisocial dimensions in the general youth population, consistent with partially shared common genetic influences. Future studies should further delineate underlying biological mechanisms.