Neurotrophin-3 as a mediator in the link between PM2.5 exposure and psychiatric disorders: A Mendelian randomization study

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. • This study used MR to link PM 2.5 and mental disorders, identifying mediators. • The study found a link between PM 2.5 and MDD, anxiety, schizophrenia, ADHD. • Neurotrophin-3 mediated 9.86 % of PM 2.5 -ADHD and 5.88 % of PM 2.5 -schizophrenia.