Associations Between Genetic Risk, Physical Activities, and Distressing Psychotic-like Experiences

Abstract

Background and hypothesis: Persistent distressing psychotic-like experiences (PLE) are associated with impaired functioning and future psychopathology. Prior research suggests that physical activities may be protective against psychopathology. However, it is unclear whether physical activities may interact with genetics in the development of psychosis.

Study design: This study included 4679 participants of European ancestry from the Adolescent Brain Cognitive Development Study. Persistent distressing PLE was derived from the Prodromal-Questionnaire-Brief Child Version using four years of data. Generalized linear mixed models tested the association between polygenic risk score for schizophrenia (PRS-SCZ), physical activities, and PLE. The models adjusted for age, sex, parental education, income-to-needs ratio, family history of psychosis, body mass index, puberty status, principal components for PRS-SCZ, study site, and family.

Study results: PRS-SCZ was associated with a greater risk for persistent distressing PLE (adjusted relative risk ratio (RRR) = 1.14, 95% CI [1.04, 1.24], P = .003). Physical activity was associated with less risk for persistent distressing PLE (adjusted RRR = 0.87, 95% CI [0.79, 0.96], P = .008). Moreover, physical activities moderated the association between PRS-SCZ and persistent distressing PLE (adjusted RRR = 0.89, 95% CI [0.81, 0.98], P = .015), such that the association was weaker as participants had greater participation in physical activities.

Conclusions: These findings demonstrate that the interaction between genetic liability and physical activities is associated with trajectories of distressing PLE. Further research is needed to understand the mechanisms of physical activities and genetic liability for schizophrenia in the development of psychosis.

Keywords: gene-environment interaction; physical activities; polygenic risk score; psychotic-like experiences; schizophrenia; team sports.

Fig. 1.

Comparison of polygenic risk score for schizophrenia among distressing PLE outcomes. Abbreviations: PLE, psychotic-like experiences; PRS-SCZ, polygenic risk score for schizophrenia. Note: There is a significant difference in the median values of PRS-SCZ between participants experiencing persistent distressing PLE and those not experiencing distressing PLE at P < .025 as denoted by *. In the boxplots, the horizontal line represents the median, the ends of the box represent the 25th (Q1) and 75th (Q3) percentiles, and the whiskers represent the minimum and maximum. Filled circles are outliers; open circles are the means.

Fig. 2.

Comparison of physical activity involvement (including team and individual sports) among distressing PLE outcomes. Abbreviations: PLE, psychotic-like experiences. Note: There is a significant difference in the median hours per week at P < .025 as denoted by *. In the boxplots, the horizontal line represents the median, the ends of the box represent the 25th (Q1) and 75th (Q3) percentiles, and the whiskers represent the minimum and maximum. Open circles are the means.

Fig. 3.

Physical activity moderates the association between polygenic risk score for schizophrenia and persistent distressing PLE. Abbreviations: PLE, psychotic-like experiences; PRS-SCZ, polygenic risk score for schizophrenia. Note: Simple slopes were calculated for the association between the interaction term, polygenic risk score for schizophrenia-by-physical activity, and persistent distressing PLE: At + 1 SD above the mean, log-odds = −0.01, 95% CI [-0.15, 0.13], P = .91. At the mean, log-odds = 0.11, 95% CI [0.01, 0.21], P = .03. At −1 SD below the mean, log-odds = 0.23, 95% CI [0.09, 0.37], P < .01.