Genetic and Geographical Associations With Six Dimensions of Psychotic Experiences in Adolesence

Abstract

Background and hypothesis: Large-scale epidemiological and genetic research have shown that psychotic experiences in the community are risk factors for adverse physical and psychiatric outcomes. We investigated the associations of six types of specific psychotic experiences and negative symptoms assessed in mid-adolescence with well-established environmental and genetic risk factors for psychosis.

Study design: Fourteen polygenic risk scores (PRS) and nine geographical environmental variables from 3590 participants of the Twins Early Development Study (mean age 16) were associated with paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and negative symptoms scales. The predictors were modeled using LASSO regularization separately (Genetic and Environmental models) and jointly (GE model).

Study results: In joint GE models, we found significant genetic associations of negative symptoms with educational attainment PRS (β = -.07; 95% CI = -0.12 to -0.04); cognitive disorganization with neuroticism PRS (β = .05; 95% CI = 0.03-0.08); paranoia with MDD (β = .07; 95% CI = 0.04-0.1), BMI (β = .05; 95% CI = 0.02-0.08), and neuroticism PRS (β = .05; 95% CI = 0.02-0.08). From the environmental measures only family SES (β = -.07, 95% CI = -0.10 to -0.03) and regional education levels (β = -.06; 95% CI = -0.09 to -0.02) were associated with negative symptoms.

Conclusions: Our findings advance understanding of how genetic propensity for psychiatric, cognitive, and anthropometric traits, as well as environmental factors, together play a role in creating vulnerability for specific psychotic experiences and negative symptoms in mid-adolescence.

Keywords: environmental risk; geographical variables; polygenic risk scores; prediction models; psychosis scales; schizophrenia.