Understanding the Interplay between Air Pollution, Biological Variables, and Major Depressive Disorder: Rationale and Study Protocol of the DeprAir Study

Abstract

Major depressive disorder (MDD) is a serious and disabling condition, whose etiological mechanisms are not fully understood. The aim of the DeprAir study is to verify the hypothesis that air pollution exposure may exacerbate neuroinflammation with consequent alterations in DNA methylation of genes involved in circadian rhythms and hormonal dysregulation, resulting in the worsening of depressive symptoms. The study population consists of 420 depressed patients accessing the psychiatry unit of the Policlinico Hospital (Milan, Italy), from September 2020 to December 2022. Data collection is still ongoing for about 100 subjects. For each participant demographic and lifestyle information, depression history and characteristics, as well as blood samples, were collected. MDD severity was assessed through five rating scales commonly used in clinical practice to assess the severity of affective symptoms. Exposure to particulate and gaseous air pollutants is assigned to each subject using both air pollution monitoring station measurements and estimates derived from a chemical transport model. DeprAir is the first study investigating in a comprehensive picture whether air pollution exposure could be an important modifiable environmental factor associated with MDD severity and which biological mechanisms mediate the negative effect of air pollution on mental health. Its results will represent an opportunity for preventive strategies, thus entailing a tremendous impact on public health.

Keywords: DNA methylation; air pollution; clock genes; hormones; inflammatory markers; major depressive disorder; nitrogen dioxide; ozone; particulate matter; sulfur dioxide.

Figure 1

DeprAir conceptual framework.

Figure 2

Graphical representation of air pollution concentration levels (NO₂ annual average for year 2021 chosen as an example). (A) Point measurements from monitoring stations expanded to the whole Lombardy territory through ordinary Kriging (used for graphical purposes only). (B) NO₂ concentrations predicted by FARM model.