The Freedom study stems from the hypothesis that exposure to urban green spaces may influence — and potentially improve — the condition of individuals affected by Major Depressive Disorder. The aim of the study is to assess how urban greenness might contribute to a more favourable progression of depressive disorder, while also investigating the possible underlying biological mechanisms.
Current literature suggests that both air pollution and the availability of green spaces for recreational use near one’s home can significantly affect depressive disorders — worsening and alleviating symptoms, respectively. Most research in this field has been conducted in the United States and China, whereas these issues still require further investigation in Southern Europe. In particular, the biological mechanisms underpinning the potential link between environment and mental health remain largely unknown.
Individuals affected by depression exhibit a series of biological changes compared to the healthy general population. Many of these changes are related to altered gene expression (epigenetics), which may be triggered by environmental factors. For this reason, investigating epigenetic alterations could be a useful strategy for understanding how the environment contributes to biological changes that modulate the severity of depressive disorder.
One of the key epigenetic regulatory mechanisms involves small RNA molecules with a regulatory function, known as microRNAs (miRNAs). These bind to gene transcripts (messenger RNA or mRNA), making them unstable and promoting their degradation. In doing so, they influence protein synthesis and, by extension, the functioning of our cells.
Another biological system influenced by the environment is the microbiota—the community of bacteria that inhabit our body. Most of these bacteria reside in the gut and play a key role in maintaining overall health. Several studies have shown that the composition of the gut microbiota is altered in individuals with depression, paving the way for new therapeutic approaches. Similarly, unhealthy lifestyles—such as physical inactivity—and environmental factors like air pollution can lead to alterations in the bacterial flora.
A minimally invasive method for studying both epigenetic changes and the microbiota involves the analysis of extracellular vesicles in the blood. Extracellular vesicles are small particles released by our cells into various biological fluids, enabling communication between distant parts of the body. These vesicles carry a range of molecules produced by the originating cell—such as proteins, lipids, and nucleic acids—which serve as biological messages to be delivered to recipient cells. In turn, recipient cells modify their metabolism and functioning in response to these messages. In recent years, the study of extracellular vesicles has garnered increasing interest, particularly because they can also contain microRNAs (miRNAs). Furthermore, they are produced by brain cells (including neurons and astrocytes) as well as by bacteria. The analysis of bacterial vesicles in the blood can therefore provide an overview of an individual's microbiota status. Additionally, isolating neuronal vesicles allows researchers to better understand how the central nervous system might regulate peripheral responses to environmental stressors.
Our hypothesis is that the presence of green spaces near one’s home may reduce the severity of depressive symptoms in individuals affected by depression. This may also occur through the modulation of the quantity, characteristics, and contents of extracellular vesicles.
To test this hypothesis, we aim to:
Assess whether extracellular vesicles derived from the central nervous system and the microbiota are associated with the severity of Major Depressive Disorder;
Investigate the relationship between air pollution exposure and the profile of extracellular vesicles;
Examine the influence of residential greenery on the severity of Major Depressive Disorder;
Explore the association between extracellular vesicles and the biological parameters previously collected as part of the DeprAir study, to evaluate their potential role in the relationship between air pollution and depression (including inflammatory and hormonal markers, as well as DNA methylation);
Evaluate whether residential greenery can influence the full set of available biological parameters we have measured;
Summarise the complex interaction between air pollution, the presence of green spaces, and all the investigated biological variables in shaping the severity of Major Depressive Disorder.
We aim to further clarify how the environment—particularly the presence of green spaces—can influence the severity of depressive symptoms through the regulation of various biological mechanisms, with a specific focus on extracellular vesicles.
Clarify the role of exposure to environmental health determinants in influencing the severity of Major Depressive Disorder.
Gain deeper insight into the biological mechanisms underlying the worsening of Major Depressive Disorder, specifically demonstrating that exposure to air pollution leads to alterations in neuron-derived extracellular vesicles.
Unravel the role of each component within the complex hypothesised framework—including air pollution, urban greenness, epigenetic, inflammatory and hormonal variables, and extracellular vesicles—in shaping the severity of Major Depressive Disorder.
Associate Professor of Occupational Medicine, Department of Clinical and Community Sciences, University of Milan. Occupational Physician, "Luigi Devoto" Occupational Health Clinic, Occupational Medicine Unit, IRCCS Ca’ Granda Foundation, Ospedale Maggiore Policlinico
Postdoctoral Research Fellow, Department of Clinical and Community Sciences, University of Milan
Coordinator for Dissemination Strategy and Interpretation of Mental Health Data. Associate Professor of Psychiatry, Department of Medical-Surgical and Transplant Physiopathology, University of Milan. Consultant Psychiatrist, Department of Neurosciences and Mental Health, IRCCS Ca’ Granda Foundation, Maggiore Policlinico Hospital
Full Professor of Forest Management and Silviculture, University of Bari Aldo Moro
This study analyzes the relationship between air pollution and content of neuron-derived extracellular vesicles in a population of patients with depression.
This study analyzes the effect of green spaces on the severity of Major Depressive Disorder, highlighting a protective effect.
This study analyzes the relationship between air pollution and content of neuron-derived extracellular vesicles in a population of patients with depression.
This study analyzes the effect of green spaces on the severity of Major Depressive Disorder, highlighting a protective effect.
