{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T02:18:07Z","timestamp":1769825887362,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione CARIPLO","doi-asserted-by":"publisher","award":["2019-3354"],"award-info":[{"award-number":["2019-3354"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijerph20065196","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T03:14:35Z","timestamp":1678936475000},"page":"5196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Understanding the Interplay between Air Pollution, Biological Variables, and Major Depressive Disorder: Rationale and Study Protocol of the DeprAir Study"],"prefix":"10.3390","volume":"20","author":[{"given":"Elisa","family":"Borroni","sequence":"first","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, Via San Barnaba 8, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0261-3252","authenticated-orcid":false,"given":"Angela Cecilia","family":"Pesatori","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, Via San Barnaba 8, 20122 Milan, Italy"},{"name":"Occupational Health Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via san Barnaba 8, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Nosari","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy"},{"name":"Department of Neurosciences and Mental Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-497X","authenticated-orcid":false,"given":"Paola","family":"Monti","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, Via San Barnaba 8, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6850-0958","authenticated-orcid":false,"given":"Alessandro","family":"Ceresa","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Fedrizzi","sequence":"additional","affiliation":[{"name":"Occupational Health Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via san Barnaba 8, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0370-9598","authenticated-orcid":false,"given":"Valentina","family":"Bollati","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, Via San Barnaba 8, 20122 Milan, Italy"},{"name":"Occupational Health Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via san Barnaba 8, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3359-3191","authenticated-orcid":false,"given":"Massimiliano","family":"Buoli","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy"},{"name":"Department of Neurosciences and Mental Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5212-2489","authenticated-orcid":false,"given":"Michele","family":"Carugno","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, Via San Barnaba 8, 20122 Milan, Italy"},{"name":"Occupational Health Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via san Barnaba 8, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41398-019-0460-3","article-title":"Prognosis and Improved Outcomes in Major Depression: A Review","volume":"9","author":"Kraus","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1590\/1516-4446-2020-0650","article-title":"Prevalence and Correlates of Major Depressive Disorder: A Systematic Review","volume":"42","author":"Dunne","year":"2020","journal-title":"Braz. J. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3928\/00989134-20150115-01","article-title":"Late Life Depression Detection: An Evidence-Based Guideline","volume":"41","author":"Smith","year":"2015","journal-title":"J. Gerontol. Nurs."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1001\/jamapsychiatry.2017.4602","article-title":"Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States","volume":"75","author":"Hasin","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114476","DOI":"10.1016\/j.psychres.2022.114476","article-title":"Gender Differences in Clinical and Biochemical Parameters of Patients Consecutively Hospitalized for Unipolar Depression","volume":"310","author":"Ceresa","year":"2022","journal-title":"Psychiatry Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1176\/appi.ajp.162.11.2116","article-title":"Risk Factors for Suicide Completion in Major Depression: A Case-Control Study of Impulsive and Aggressive Behaviors in Men","volume":"162","author":"Dumais","year":"2005","journal-title":"Am. J. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S2215-0366(21)00395-3","article-title":"Global, Regional, and National Burden of 12 Mental Disorders in 204 Countries and Territories, 1990\u20132019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"9","author":"Ferrari","year":"2022","journal-title":"Lancet Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s12264-021-00638-3","article-title":"Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications","volume":"37","author":"Li","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"577959","DOI":"10.1016\/j.jneuroim.2022.577959","article-title":"The Pathophysiology of Major Depressive Disorder through the Lens of Systems Biology: Network Analysis of the Psycho-Immune-Neuroendocrine Physiome","volume":"372","author":"Stapelberg","year":"2022","journal-title":"J. Neuroimmunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/15622975.2016.1208843","article-title":"Consensus Paper of the WFSBP Task Force on Genetics: Genetics, Epigenetics and Gene Expression Markers of Major Depressive Disorder and Antidepressant Response","volume":"18","author":"Fabbri","year":"2016","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_12","first-page":"21","article-title":"Genome-Wide Meta-Analysis of Depression Identifies 102 Independent Variants and Highlights the Importance of the Prefrontal Brain Regions","volume":"13","author":"Howard","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cambria, C., Ingegnoli, F., Borzi, E., Cantone, L., Coletto, L.A., Rizzuto, A.S., De Lucia, O., Briguglio, S., Ruscica, M., and Caporali, R. (2022). Synovial Fluid-Derived Extracellular Vesicles of Patients with Arthritides Contribute to Hippocampal Synaptic Dysfunctions and Increase with Mood Disorders Severity in Humans. Cells, 11.","DOI":"10.3390\/cells11152276"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Charrier, A., Olliac, B., Roubertoux, P., and Tordjman, S. (2017). Clock Genes and Altered Sleep\u2013Wake Rhythms: Their Role in the Development of Psychiatric Disorders. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050938"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Iodice, S., Ceresa, A., Esposito, C.M., Mucci, F., Conti, D.M., Pergoli, L., Tarantini, L., Vigna, L., Bollati, V., and Buoli, M. (2021). The Independent Role of Body Mass Index (BMI) and Severity of Depressive Symptoms on Biological Changes of Women Affected by Overweight\/Obesity and Stand-Up Project Group. Public Health, 18.","DOI":"10.3390\/ijerph18062923"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118809","DOI":"10.1016\/j.lfs.2020.118809","article-title":"The Circadian Machinery Links Metabolic Disorders and Depression: A Review of Pathways, Proteins and Potential Pharmacological Interventions","volume":"265","author":"Pitsillou","year":"2021","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nrgastro.2016.8","article-title":"Circadian Rhythms of Liver Physiology and Disease: Experimental and Clinical Evidence","volume":"13","author":"Tahara","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sato, F., Kohsaka, A., Bhawal, U.K., and Muragaki, Y. (2018). Potential Roles of Dec and Bmal1 Genes in Interconnecting Circadian Clock and Energy Metabolism. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030781"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1017\/S0029665116000628","article-title":"Circadian Rhythms, Food Timing and Obesity","volume":"75","author":"Garaulet","year":"2016","journal-title":"Proc. Nutr. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2217\/epi.11.22","article-title":"Epigenetics and Lifestyle","volume":"3","author":"Baccarelli","year":"2011","journal-title":"Epigenomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/0748730414553971","article-title":"Adrenal Clocks and the Role of Adrenal Hormones in the Regulation of Circadian Physiology","volume":"30","author":"Leliavski","year":"2015","journal-title":"J. Biol. Rhythm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/nyas.12781","article-title":"Neuroimmune and Neuroendocrine Abnormalities in Depression: Two Sides of the Same Coin","volume":"1351","author":"Horowitz","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_23","first-page":"4195","article-title":"Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis","volume":"55","author":"Freitas","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1124\/jpet.116.237503","article-title":"Oxidative Stress and the Central Nervous System","volume":"360","author":"Salim","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.euroneuro.2017.04.001","article-title":"Why Are Depressed Patients Inflamed? A Reflection on 20 Years of Research on Depression, Glucocorticoid Resistance and Inflammation","volume":"27","author":"Pariante","year":"2017","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1080\/08039488.2020.1751878","article-title":"Obstetric Complications and Subsequent Risk of Mood Disorders for Offspring in Adulthood: A Comprehensive Overview","volume":"74","author":"Serati","year":"2020","journal-title":"Nord. J. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.genhosppsych.2022.03.008","article-title":"Childhood Adversity and Adulthood Major Depressive Disorder","volume":"76","author":"Zisook","year":"2022","journal-title":"Gen. Hosp. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S0140-6736(11)61878-3","article-title":"Urbanisation and Health in China","volume":"379","author":"Gong","year":"2012","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118245","DOI":"10.1016\/j.envpol.2021.118245","article-title":"Air Pollution Exposure and Depression: A Comprehensive Updated Systematic Review and Meta-Analysis","volume":"292","author":"Borroni","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1016\/j.jmb.2019.12.044","article-title":"Molecular Interactions Between Components of the Circadian Clock and the Immune System","volume":"432","author":"Hergenhan","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2101251","DOI":"10.1002\/advs.202101251","article-title":"An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models","volume":"8","author":"Kang","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cugurra, A., Mamuladze, T., Rustenhoven, J., Dykstra, T., Beroshvili, G., Greenberg, Z.J., Baker, W., Papadopoulos, Z., Drieu, A., and Blackburn, S. (2021). Skull and Vertebral Bone Marrow Are Myeloid Cell Reservoirs for the Meninges and CNS Parenchyma. Science, 373.","DOI":"10.1126\/science.abf7844"},{"key":"ref_33","unstructured":"Fossati, A., and Borroni, S. (2017). SCID-5-CV\u2014Intervista Clinica Strutturata per i Disturbi Del DSM-5\u00ae, Raffaello Cortina Editore."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/mpr.1388","article-title":"The Structure of the Montgomery-\u00c5sberg Depression Rating Scale over the Course of Treatment for Depression","volume":"22","author":"Quilty","year":"2013","journal-title":"Int. J. Methods Psychiatr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1093\/occmed\/kqv043","article-title":"The Hamilton Rating Scale for Depression","volume":"65","author":"Sharp","year":"2015","journal-title":"Occup. Med."},{"key":"ref_36","first-page":"28","article-title":"The Clinical Global Impressions Scale: Applying a Research Tool in Clinical Practice","volume":"4","author":"Busner","year":"2007","journal-title":"Psychiatry"},{"key":"ref_37","first-page":"887","article-title":"Psychometric Evaluation of the Sheehan Disability Scale in Adult Patients with Attention-Deficit\/Hyperactivity Disorder","volume":"10","author":"Coles","year":"2014","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1744-859X-10-2","article-title":"Guidelines for Rating Global Assessment of Functioning (GAF)","volume":"10","author":"Aas","year":"2011","journal-title":"Ann. Gen. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.envsoft.2007.04.002","article-title":"Modelling of PM10 Concentrations over Milano Urban Area Using Two Aerosol Modules","volume":"23","author":"Silibello","year":"2008","journal-title":"Environ. Model. Softw."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.atmosenv.2013.11.006","article-title":"Assessment of the AMS-MINNI System Capabilities to Simulate Air Quality over Italy for the Calendar Year 2005","volume":"84","author":"Mircea","year":"2014","journal-title":"Atmos. Environ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12667","DOI":"10.5194\/acp-16-12667-2016","article-title":"Presentation of the EURODELTA III Intercomparison Exercise-Evaluation of the Chemistry Transport Models\u2019 Performance on Criteria Pollutants and Joint Analysis with Meteorology","volume":"16","author":"Bessagnet","year":"2016","journal-title":"Atmos. Chem. Phys."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5194\/acp-12-1-2012","article-title":"A Review of Operational, Regional-Scale, Chemical Weather Forecasting Models in Europe","volume":"12","author":"Kukkonen","year":"2012","journal-title":"Atmos. Chem. Phys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1037\/a0031034","article-title":"Mediation Analysis Allowing for Exposure-Mediator Interactions and Causal Interpretation: Theoretical Assumptions and Implementation with SAS and SPSS Macros","volume":"18","author":"Valeri","year":"2013","journal-title":"Psychol. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bollati, V., Iodice, S., Favero, C., Angelici, L., Albetti, B., Cacace, R., Cantone, L., Carugno, M., Cavalleri, T., and De Giorgio, B. (2014). Susceptibility to Particle Health Effects, MiRNA and Exosomes: Rationale and Study Protocol of the SPHERE Study. BMC Public Health, 14.","DOI":"10.1186\/1471-2458-14-1137"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1017\/S2045796019000088","article-title":"Translating the BDI and BDI-II into the HAMD and Vice Versa with Equipercentile Linking","volume":"29","author":"Furukawa","year":"2020","journal-title":"Epidemiol. Psychiatr. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"110943","DOI":"10.1016\/j.envres.2021.110943","article-title":"Short-Term Air Pollution Exposure Is Associated with Lower Severity and Mixed Features of Manic Episodes in Hospitalized Bipolar Patients: A Cross-Sectional Study in Milan, Italy","volume":"196","author":"Carugno","year":"2021","journal-title":"Environ. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.envres.2018.06.016","article-title":"PM10 Exposure Is Associated with Increased Hospitalizations for Respiratory Syncytial Virus Bronchiolitis among Infants in Lombardy, Italy","volume":"166","author":"Carugno","year":"2018","journal-title":"Environ. Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ferrari, L., Borghi, F., Iodice, S., Catelan, D., Rossi, S., Giusti, I., Grisotto, L., Rovelli, S., Spinazz\u00e8, A., and Alinovi, R. (2020). INSIDE Project: Individual Air Pollution Exposure, Extracellular Vesicles Signaling and Hypertensive Disorder Development in Pregnancy. Int. J. Environ. Res. 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