Genetic insights into the effect of Metformin on psychiatry disorders.

Objective: This study employs Mendelian Randomization (MR) to explore the causal relationships between Metformin and 20 mental illnesses. The aim is to provide new pharmacological treatment bases for the treatment and intervention of mental illnesses, thereby reducing incidence rates and alleviating the disease burden.

Methods: This study uses summarized data from Genome Wide Association Studies (GWAS) to identify genetic instrumental variables (IVs) that are significantly associated with Metformin and are mutually independent. The primary method used to evaluate causal relationships is the Inverse Variance Weighted (IVW) approach, complemented by other MR methods for sensitivity analysis.

Results: MR analysis results indicate a significant negative causal relationship between genetically predicted Metformin and Neuroticism(NEU) (OR = 0.700, 95% CI: 0.505-0.970, P = 0.032) and Bipolar Disorder(BID) (OR = 0.0374, 95% CI: 0.00266-0.525, P = 0.015). Additionally, a significant positive causal relationship was found with Attention deficit hyperactivity disorder(ADHD) (OR = 15.4, 95% CI: 1.95-122, P = 0.010) and Insomnia(INS) (OR = 1.96E + 06, 95% CI: 351-1.10E + 10, P = 0.001). There were no significant causal relationships with the remaining mental illnesses (P>0.05). Sensitivity analyses indicate that the results are robust.

Conclusion: From a genetic perspective, this study finds that Metformin may reduce the risk of NEU and BID while increasing the risk of ADHD and INS. These findings not only provide theoretical support for further research into the etiological mechanisms but also offer valuable reference points for the clinical use of Metformin in treating NEU and BID, and for exercising caution in its use among patients with ADHD and INS.