Causal Relationships Between Mental Health Disorders and Parkinson's Disease: A Mendelian Randomization Study

Parkinson's disease (PD), a neurodegenerative disorder, is increasingly being linked to various comorbid conditions, including mental health disorders. This study aims to evaluate the potential causal associations between genetically predicted mental health disorders and the likelihood of developing PD.

A bidirectional Mendelian randomization (MR) approach was applied using genetic variants identified from large-scale genome-wide association study as instrumental variables. Multiple MR methodologies, including inverse variance weighted, MR-Egger, and weighted median analyses, were employed to mitigate potential biases such as pleiotropy and provide robust evidence of causal relationships between mental health conditions and PD.

The MR analysis revealed a significant causal link between personality disorders and PD (OR = 1.9901, 95% CI: 1.105-3.5842, P = .0219), suggesting that personality disorders may contribute to the development of PD. However, no significant causal associations were found between PD and other mental health conditions, such as obsessive-compulsive disorder, attention deficit hyperactivity disorder, bipolar disorder, depression, and schizophrenia (P > .05 for all).

This study suggests that personality disorders may be involved in the pathogenesis of PD, offering novel insights into the potential impact of mental health on neurodegenerative diseases. These findings lay the foundation for further exploration of the biological mechanisms linking mental health conditions and PD, with potential implications for both psychiatric and neurodegenerative disease management.