Physical activity may not mitigate schizophrenia risk

Physical activity did not appear to have preventive effects for schizophrenia, according to results of a two-sample mendelian randomization analysis published in JAMA Psychiatry.

“Substantial evidence indicates that physical activity improves symptoms, cognitive function and quality of life in patients with schizophrenia,” Sergi Papiol, PhD, of the department of psychiatry at the University Hospital of Munich in Germany, and colleagues wrote. “Some studies suggest a protective effect of [physical activity] against schizophrenia/psychosis risk itself, although current evidence is inconclusive.”

The researchers used mendelian randomization and its multivariable extension to assess the link between physical activity and schizophrenia risk. Further, they evaluated the potential pleiotropic role of BMI in this interplay, since it serves as a common confounder in studies that involve physical activity. They extracted instrumental variables from summary of U.K. biobank genome-wide-association studies that included accelerometer-based physical activity of more than 90,000 individuals and self-reported physical activity of a minimum of 261,055 participants and a maximum of 377,234 participants. Papiol and colleagues also extracted instrumental variables for 40,675 schizophrenia cases and 64,643 controls, as well as BMI of 339,224 individuals, from their respective genome-wide-association studies.

The researchers observed no association between physical activity and schizophrenia risk in any of their analyses. Self-reported moderate/vigorous physical activity appeared associated with increased schizophrenia risk according to univariate analysis with and without BMI correction. They obtained similar results with mendelian randomization multivariable extension using BMI as a covariate. Further, they noted a similar trend in the univariate analysis based on overall activity; however, the association was not significant after correction for BMI. According to sensitivity analyses, horizontal pleiotropy, heterogeneity or individual single nucleotide polymorphism effects were not likely to confound the moderate/vigorous physical activity results.

“The potential implications of our results for disease prevention policies warrant the validation of these findings in well-powered cohort studies,” Papiol and colleagues wrote.