Neurotrophin-3 as a mediator in the link between PM_2.5 exposure and psychiatric disorders: A Mendelian randomization...

The causal relationship between PM_2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm) and common mental disorders, along with its neuropathological mechanisms, remains unclear.

We used genome-wide association study datasets from the UK Biobank and Psychiatric Genomics Consortium to systematically investigate the causal relationship between PM_2.5 and nine common psychiatric disorders using two-sample Mendelian randomization (TSMR) methods. Subsequently, we used two-step MR to investigate the mediating effect of 108 potential mediators in the association between PM_2.5 and mental disorders.

Our findings indicated that PM_2.5 was positively associated with major depressive disorder (odds ratio (OR): 1.33, 95 % confidence interval (CI): 1.11-1.55), anxiety disorder (OR: 2.96, 95 % CI: 2.13-3.79), schizophrenia (OR: 1.55, 95 % CI: 1.29-1.81), and attention deficit hyperactivity disorder (ADHD) (OR: 1.95, 95 % CI: 1.66-2.24). Unexpectedly, PM_2.5 was inversely associated with bipolar disorder (OR: 0.65, 95 % CI: 0.37-0.93). Additionally, PM_2.5 was not significantly associated with autism spectrum disorders (OR: 1.24, 95 % CI: 0.83-1.65), post-traumatic stress disorder (OR: 1.51, 95 % CI: 1.11-1.91), obsessive-compulsive disorder (OR: 0.81, 95 % CI: -0.07-1.69), or anorexia nervosa (OR: 1.42, 95 % CI: 0.86-1.98). Further analysis using two-step MR revealed that Neurotrophin-3 mediated 9.86 % of the PM_2.5-ADHD association and 5.88 % of the PM_2.5-schizophrenia association. Sensitivity analyses supported these findings.

This TSMR analysis provides a comprehensive examination of the causal relationship between PM_2.5 exposure and nine common psychiatric disorders, with mediation analysis offering insight into the underlying mechanisms. This study aims to raise public awareness of how air quality affects mental health through empirical evidence.