Can Polygenic Risk Scores for Metabolic Syndrome Contribute to Long-Term Syndrome Development in First-Episode Psychosis Patients? A Naturalistic 21-Year Follow-Up Study.

Background and hypothesis: Metabolic syndrome (MetS) is still a challenge for clinicians treating patients with first-episode psychosis (FEP).

Study design: We explored whether polygenic risk scores for MetS (PRSMetS) may be associated with MetS in FEP patients. The sample comprised 164 FEP patients who were followed-up for a mean of 20.9 years. MetS was defined according to the ATP III criteria at the end of the follow-up. We used logistic regression models to examine the contribution of PRSs for the development of MetS and associated metabolic symptoms after allowing for the effect of covariates. Furthermore, we investigated the relationships between PRSMetS and metabolic symptoms using network analysis (NA).

Study results: PRSMetS significantly contributed to the development of MetS and the increase of waist circumference at the long-term follow-up, accounting for 7.9% and 6.8% of the explained variance, respectively. Moreover, the PRS of high-density lipoprotein cholesterol levels showed a significant association value for hypertension, accounting for 5.6% of the variance.PRSMetS showed a significant linear trend with the number of MetS criteria and this trend remained significant after allowing for standard epidemiological and clinical baseline variables in the hierarchical multiple regression analysis. PRSMetS, PRSWaist, and the five metabolic criteria showed rich interconnections in the network analysis.

Conclusions: MetS PRSs showed significant relationships with metabolic disturbances in patients with FEP over a lifetime. Our findings may offer promising avenues for the PRSMetS to be integrated with relevant clinical measures for identifying the FEP patients most vulnerable to develop MetS.