{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:32:19Z","timestamp":1784129539377,"version":"3.55.0"},"reference-count":92,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T00:00:00Z","timestamp":1707004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health (Ricerca Corrente 2022-2024 IRCCS Mondino Foundation, Pavia)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Resistant migraine characterizes those patients who have failed at least three classes of migraine prophylaxis. These difficult-to-treat patients are likely to be characterized by a high prevalence of psychological disturbances. A dysfunction of the endocannabinoid system (ECS), including alteration in the levels of endocannabinoid congeners, may underlie several psychiatric disorders and the pathogenesis of migraines. Here we explored whether the peripheral gene expression of major components of the ECS and the plasma levels of endocannabinoids and related lipids are associated with psychological disorders in resistant migraine. Fifty-one patients (age = 46.0 \u00b1 11.7) with resistant migraine received a comprehensive psychological evaluation according to the DSM-5 criteria. Among the patients, 61% had personality disorders (PD) and 61% had mood disorders (MD). Several associations were found between these psychological disorders and peripheral ECS alterations. Lower plasma levels of palmitoiletanolamide (PEA) were found in the PD group compared with the non-PD group. The MD group was characterized by lower mRNA levels of diacylglycerol lipase \u03b1 (DAGL\u03b1) and CB2 (cannabinoid-2) receptor. The results suggest the existence of peripheral dysfunction in some components of the ECS and an alteration in plasma levels of PEA in patients with resistant migraine and mood or personality disorders.<\/jats:p>","DOI":"10.3390\/ijms25031893","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T05:22:44Z","timestamp":1707110564000},"page":"1893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Peripheral Endocannabinoid Components and Lipid Plasma Levels in Patients with Resistant Migraine and Co-Morbid Personality and Psychological Disorders: A Cross-Sectional Study"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-3962","authenticated-orcid":false,"given":"Sara","family":"Bottiroli","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-0629","authenticated-orcid":false,"given":"Rosaria","family":"Greco","sequence":"additional","affiliation":[{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Franco","sequence":"additional","affiliation":[{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Clinical and Experimental Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Zanaboni","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Palmisani","sequence":"additional","affiliation":[{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Clinical and Experimental Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0117-7126","authenticated-orcid":false,"given":"Gloria","family":"Vaghi","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8257-2886","authenticated-orcid":false,"given":"Grazia","family":"Sances","sequence":"additional","affiliation":[{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-4948","authenticated-orcid":false,"given":"Roberto","family":"De Icco","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-2113","authenticated-orcid":false,"given":"Cristina","family":"Tassorelli","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/S0140-6736(20)32162-0","article-title":"Migraine: Disease Characterisation, Biomarkers, and Precision Medicine","volume":"397","author":"Ashina","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/j.1526-4610.2008.01132.x","article-title":"Defining Refractory Migraine and Refractory Chronic Migraine: Proposed Criteria From the Refractory Headache Special Interest Section of the American Headache Society","volume":"48","author":"Schulman","year":"2008","journal-title":"Headache J. 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