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

Area of Science:

• Psychiatry
• Genetics
• Neuroscience

Background:

• Persistent distressing psychotic-like experiences (PLE) are linked to impaired functioning and future psychopathology.
• Physical activity shows potential protective effects against psychopathology.
• The interaction between physical activity and genetic predisposition in psychosis development remains under-explored.

Purpose of the Study:

• To investigate the association between genetic liability for schizophrenia, physical activity, and persistent distressing PLE.
• To examine whether physical activity moderates the relationship between genetic risk and PLE.

Main Methods:

• Utilized data from 4679 participants of European ancestry in the Adolescent Brain Cognitive Development Study.
• Persistent distressing PLE was assessed over four years using the Prodromal-Questionnaire-Brief Child Version.
• Generalized linear mixed models analyzed the interplay of polygenic risk score for schizophrenia (PRS-SCZ) and physical activity, adjusting for multiple covariates.

Main Results:

• A higher PRS-SCZ was associated with an increased risk of persistent distressing PLE (RRR=1.14, P=.003).
• Increased physical activity was linked to a reduced risk of persistent distressing PLE (RRR=0.87, P=.008).
• Physical activity significantly moderated the PRS-SCZ association with PLE, weakening the link as activity levels increased (RRR=0.89, P=.015).

Conclusions:

• The interaction between genetic liability and physical activity influences the trajectory of distressing PLE.
• Findings suggest physical activity may be a protective factor, particularly for individuals with higher genetic risk for schizophrenia.
• Further research is warranted to elucidate the specific mechanisms underlying these interactions in psychosis development.