{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:45:50Z","timestamp":1768484750516,"version":"3.49.0"},"reference-count":66,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-Next Generation EU-NRRP M6C2-Investment 2.1 Enhancement and strengthening of biomedical research in the NHS","award":["PNRRMAD-2022-12376693"],"award-info":[{"award-number":["PNRRMAD-2022-12376693"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study investigated the complexity of neurotransmitter-related gene regulation in peripheral blood mononuclear cells (PBMCs) of patients with obsessive\u2013compulsive disorder (OCD), aiming to identify clinically relevant molecular markers. We analyzed three key genes: SLC6A4 (serotonin transporter), MAOB (monoamine oxidase B, a dopamine-degrading enzyme), and COMT (catechol-O-methyltransferase, a dopamine\/norepinephrine metabolizing enzyme). OCD patients exhibited significant downregulation of SLC6A4 and MAOB, accompanied by upregulation of MB-COMT. The contrasting expression of MAOB and MB-COMT suggests a dysregulated compensatory mechanism in dopamine homeostasis, which contributes to clinical heterogeneity and variability in treatment for OCD. Epigenetic analysis revealed that downregulation of SLC6A4 was associated with hypermethylation of the gene promoter, demonstrating the critical role of epigenetic mechanisms in neurotransmitter system dysregulation. Moreover, gene\u2013gene correlations identified distinctive molecular expression patterns that reliably discriminated OCD patients from healthy individuals, proposing their potential as peripheral biomarkers. In conclusion, serotonergic and dopaminergic abnormalities characterize OCD, where epigenetic regulation contributes to gene dysregulation. The identified molecular signatures may explain the inefficiency of treatments and support biomarker-guided clinical approaches. Given that peripheral gene regulation and core neurotransmitter systems are similar, this study contributes to the biological picture of OCD, indicating the accuracy of diagnoses and treatments.<\/jats:p>","DOI":"10.3390\/ijms26188811","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T12:04:55Z","timestamp":1757505895000},"page":"8811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Peripheral Blood Biomarkers Reveal Dysregulated Monoaminergic Pathways in Obsessive\u2013Compulsive Disorder: A Transcriptional and Epigenetic Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8443-6084","authenticated-orcid":false,"given":"Fabio","family":"Bellia","sequence":"first","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolaja","family":"Girone","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0539-7150","authenticated-orcid":false,"given":"Beatrice","family":"Benatti","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy"},{"name":"\u201cAldo Ravelli\u201d Center for Nanotechnology and Neurostimulation, University of Milan, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Vismara","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Pettorruso","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Imaging, \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7292-2341","authenticated-orcid":false,"given":"Giovanni","family":"Martinotti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Imaging, \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardo","family":"Dell\u2019Osso","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy"},{"name":"\u201cAldo Ravelli\u201d Center for Nanotechnology and Neurostimulation, University of Milan, 20157 Milan, Italy"},{"name":"Bipolar Disorders Clinic in the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1275-098X","authenticated-orcid":false,"given":"Claudio","family":"D\u2019Addario","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4657-6075","authenticated-orcid":false,"given":"Mariangela","family":"Pucci","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"784","DOI":"10.4088\/JCP.09m05911blu","article-title":"Quality of Life Outcomes in Patients with Obsessive-Compulsive Disorder: Relationship to Treatment Response and Symptom Relapse","volume":"71","author":"Hollander","year":"2010","journal-title":"J. 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