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

Yuan Zhang; Wei Wang; Xuening Zhang; Ran Jing; Xin Wen; Peng Xiao; Xinjie Liu; Zengle Zhao; Tongmin Chang; Yufei Li; Wen Liu; Chenxi Sun; Xiaorong Yang; Lejin Yang; Ming Lu

doi:10.1016/j.ecoenv.2024.117658

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

Ecotoxicol Environ Saf. 2025 Jan 6:289:117658. doi: 10.1016/j.ecoenv.2024.117658. Online ahead of print.

Authors

Yuan Zhang¹, Wei Wang², Xuening Zhang¹, Ran Jing³, Xin Wen⁴, Peng Xiao⁵, Xinjie Liu¹, Zengle Zhao¹, Tongmin Chang¹, Yufei Li¹, Wen Liu⁶, Chenxi Sun⁷, Xiaorong Yang⁸, Lejin Yang⁹, Ming Lu¹⁰

Affiliations

¹ School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Psychology, Qilu Hospital of Shandong University, Jinan, China.
³ Psychology department, Mount Holyoke College, South Hadley, MA, USA.
⁴ NHC Key Laboratory of Otorhinolaryngology, Qilu hospital and School of Basic Medical Sciences, Shandong University, Jinan, China; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, China.
⁵ Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, China.
⁶ The First Clinical School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁷ Department of Anatomy and Neurobiology, Research Center for Sectional and Imaging Anatomy, Shandong Key Laboratory of Mental Disorders, Shandong Key Laboratory of Digital Human and Clinical Anatomy, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁸ Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center of Shandong University, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: [email protected].
⁹ Department of Psychology, Qilu Hospital of Shandong University, Jinan, China. Electronic address: [email protected].
¹⁰ School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China; Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center of Shandong University, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: [email protected].

PMID: 39765118
DOI: 10.1016/j.ecoenv.2024.117658

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Anxiety disorder; Major depressive disorder; Mendelian randomization; Mental disorders; PM(2.5); Schizophrenia.