Causal relationship between PM2.5 exposure and population-level antidepressant medication use: A Mendelian...

Area of Science:

• Environmental Epidemiology
• Psychiatric Genetics
• Toxicology

Background:

• Fine particulate matter (PM2.5) exposure is linked to depression, but causal evidence is limited.
• Antidepressant medication use serves as a population-level proxy for clinically managed depressive symptom burden.

Purpose of the Study:

• To investigate the causal relationship between genetically predicted chronic PM2.5 exposure and antidepressant medication use.
• To assess if PM2.5 exposure increases the likelihood of requiring treatment for depression.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data.
• Instrumental variables derived from 48 SNPs associated with PM2.5 exposure.
• Inverse-variance weighted (IVW) method and sensitivity analyses were employed.

Main Results:

• Genetically predicted PM2.5 exposure was significantly associated with increased antidepressant use (OR=1.496, p<0.001).
• Results were consistent across various MR methods.
• Sensitivity analyses ruled out significant directional pleiotropy or influential outliers.

Conclusions:

• This MR study provides genetic evidence for a causal link between chronic PM2.5 exposure and higher antidepressant use.
• Reducing air pollution may be a viable strategy to decrease the global burden of depression.