Gene-Environment Pathways to Cognitive Intelligence and Psychotic-Like Experiences in Children

Abstract

In children, psychotic-like experiences (PLEs) are related to risk of psychosis, schizophrenia, and other mental disorders. Maladaptive cognitive functioning is a well-known risk factor and early marker for psychosis, schizophrenia, and other mental disorders. Since cognitive functioning is linked to various genetic and environmental factors during development, we hypothesize that it mediates the effects of those factors on childhood PLEs. Using large longitudinal data, we tested the relationships of genetic and environmental factors (such as familial and neighborhood environment) with cognitive intelligence and their relationships with current and future PLEs in children. To estimate associations against potential confounding bias, we leveraged large-scale multimodal data of 6,602 children (aged 9-10 years old; 47.15% females; 5,211 European-ancestry) from the Adolescent Brain and Cognitive Development Study. Linear mixed model and a novel structural equation modeling (SEM) method that allows estimation of both components and factors were used to estimate the joint effects of cognitive phenotypes polygenic scores (PGSs), familial and neighborhood socioeconomic status (SES), and supportive environment on NIH Toolbox cognitive intelligence and PLEs. We adjusted for ethnicity (genetically defined), schizophrenia PGS, and additionally unobserved confounders (using computational confound modeling). We identified that lower cognitive intelligence and higher PLEs correlated significantly with several genetic and environmental variables: i.e., lower PGSs for cognitive phenotypes, lower familial SES, lower neighborhood SES, lower supportive parenting behavior, and lower positive school environment. In SEM, lower cognitive intelligence significantly mediated the genetic and environmental influences on higher PLEs (Indirect effects of PGS: β range=-0.0355~ -0.0274; Family SES: β range=-0.0429~ -0.0331; Neighborhood SES: β range=0.0126~ 0.0164; Positive Environment: β range=-0.0039~ -0.003). Supportive parenting and a positive school environment had the largest total impact on PLEs (β range=-0.152~ -0.1316) than any other genetic or environmental factors. Our results reveal the role of genetic and environmental factors on children’s PLEs via its negative impact on cognitive intelligence. Our findings have policy implications in that improving the school and family environment and promoting local economic development might be a way to enhance cognitive and mental health in children. While existing research shows the association between cognitive decline and PLEs, the genetic and environmental pathways to cognitive intelligence and psychotic risk in children remain unclear. We identified the significant role of genetic and environmental factors (family, neighborhood, and school) on children’s PLEs via a negative impact on cognitive intelligence. Leveraging large samples with multimodal longitudinal data and advanced computational modeling for adjustment of observed/unobserved confounding bias, our results underscore the importance of incorporating socioeconomic policies into children’s cognitive and mental health programs.