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

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 healt