Genetic liability for schizophrenia and childhood psychopathology in the general population

Background Genetic liability for schizophrenia is associated with psychopathology in early life. It is not clear if these associations are time-dependent during childhood, nor if they are specific across different forms of psychopathology. Methods Using genotype and questionnaire data on children (N = 15,105) from the Norwegian Mother, Father, and Child Cohort Study (MoBa), we tested associations between schizophrenia polygenic risk scores and measures of childhood emotional and behavioural problems for developmental stability and domain specificity. We then sought to identify symptom profiles, across development and domains, associated with elevated schizophrenia polygenic liability. Results. We found evidence for developmental stability in associations between schizophrenia polygenic risk scores and emotional and behavioural problems, with the latter being mediated via the rate of change in symptoms between 18 months and 5 years specifically (B = 0.032; 95% CI 0.007-0.057). At age 8, associations with emotional and behavioural psychopathology were found to be better explained by a model of symptom-specific polygenic risk score effects, rather than effects mediated via a general p factor or by domain-specific factors. Overall, individuals with higher schizophrenia polygenic risk scores were more likely (OR= 1.310 [95% CIs: 1.122-1.528]) to have increasing behavioural and emotional symptoms in early childhood, followed by relatively elevated symptoms of conduct disorder, oppositional defiant disorder, hyperactivity and inattention in middle childhood. Interpretation Schizophrenia-associated alleles are linked to specific patterns of early-life psychopathology. The associations are small, but findings of this nature can help us better understand the developmental emergence of schizophrenia.