{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:08:45Z","timestamp":1791821325221,"version":"4.3.4"},"reference-count":463,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Migraine is a highly prevalent neurological disorder. Among the risk factors identified, psychiatric comorbidities, such as depression, seem to play an important role in its onset and clinical course. Patients with migraine are 2.5 times more likely to develop a depressive disorder; this risk becomes even higher in patients suffering from chronic migraine or migraine with aura. This relationship is bidirectional, since depression also predicts an earlier\/worse onset of migraine, increasing the risk of migraine chronicity and, consequently, requiring a higher healthcare expenditure compared to migraine alone. All these data suggest that migraine and depression may share overlapping biological mechanisms. Herein, this review explores this topic in further detail: firstly, by introducing the common epidemiological and risk factors for this comorbidity; secondly, by focusing on providing the cumulative evidence of common biological aspects, with a particular emphasis on the serotoninergic system, neuropeptides such as calcitonin-gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, neuropeptide Y and orexins, sexual hormones, and the immune system; lastly, by remarking on the future challenges required to elucidate the etiopathological mechanisms of migraine and depression and providing updated information regarding new key targets for the pharmacological treatment of these clinical entities.<\/jats:p>","DOI":"10.3390\/biom14020163","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T03:45:12Z","timestamp":1706586312000},"page":"163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Understanding the Biological Relationship between Migraine and Depression"],"prefix":"10.3390","volume":"14","author":[{"given":"Adri\u00e1n","family":"Viudez-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Hospital Pharmacy Service, Hospital General Dr. Balmis de Alicante, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham B.","family":"Torregrosa","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"},{"name":"Research Network on Primary Addictions, Instituto de Salud Carlos III, MICINN and FEDER, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1251-6357","authenticated-orcid":false,"given":"Francisco","family":"Navarrete","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"},{"name":"Research Network on Primary Addictions, Instituto de Salud Carlos III, MICINN and FEDER, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6106-6247","authenticated-orcid":false,"given":"Mar\u00eda Salud","family":"Garc\u00eda-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"},{"name":"Research Network on Primary Addictions, Instituto de Salud Carlos III, MICINN and FEDER, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1111\/head.12150","article-title":"Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: Results of the American Migraine Prevalence and Prevention (AMPP) Study","volume":"53","author":"Buse","year":"2013","journal-title":"Headache"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1046\/j.1468-1331.2003.00551.x","article-title":"Depression and anxiety disorders associated with headache frequency. 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