{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:51:38Z","timestamp":1787849498142,"version":"build-2784847793"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Houston Methodist Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Objective: Genetic and environmental factors influence the expression of personality pathology and subsequent treatment efforts. This study associates genetics with a contemporary nosology of personality pathology represented in the Alternative Model for Personality Disorders (AMPD). We hypothesized traits from Criterion B of the AMPD would differ between genotypes of the catechol-O-methyltransferase (COMT) polymorphism (rs4680\/Val158Met variation), given this genetic marker\u2019s role in the metabolism of dopamine and norepinephrine, especially in the prefrontal cortex. Methods: The Personality Inventory for DSM-V (PID-5) was used to quantify personality traits, and the Genomind platform was used to identify the genotypes of the Val158Met COMT polymorphism in 84 psychiatric outpatients. Results: One of the five Criterion B personality domains and three of the twenty-five traits were significantly different among genotypes. Met\/Met carriers had significantly higher pathological scores on the broad domain of negative affect and specific traits of perceptual dysregulation and separation insecurity, while the Val\/Val carriers had significantly higher scores on the restricted affectivity trait. The COMT Val158Met polymorphism\u2019s association with personality pathology was sexually dimorphic, with the two domains and nine traits significantly different across genotypes in males, but no differences were found in females. A substantial improvement in the regression of domains\/traits score when gene\u2013sex interactions were included further confirmed the dimorphism, e.g., the R-squared (adjusted) for the psychoticism improved from 0.03 (p = 0.15) to 0.19 (p &lt; 0.001). Conclusions: Findings offer preliminary support for a link, potentially dimorphic across sexes, between the COMT Val158Met polymorphism and personality pathology as represented by the AMPD.<\/jats:p>","DOI":"10.3390\/brainsci15121337","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T11:00:26Z","timestamp":1765882826000},"page":"1337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sexually Dimorphic Association of Catechol-O-Methyltransferase (COMT) Functional Polymorphism with Dimensional Personality Pathology: A Preliminary Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0065-0247","authenticated-orcid":false,"given":"John T.","family":"Rucker","sequence":"first","affiliation":[{"name":"The Austen Riggs Center, Stockbridge, MA 01262, USA"},{"name":"Menninger Department of Psychiatry and Behavioral Health, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishal","family":"Lamichhane","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Haren","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9119-5410","authenticated-orcid":false,"given":"Benjamin L.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-5206","authenticated-orcid":false,"given":"Alok","family":"Madan","sequence":"additional","affiliation":[{"name":"Menninger Department of Psychiatry and Behavioral Health, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX 77030, USA"},{"name":"Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.copsyc.2020.12.005","article-title":"Five Failures and Five Challenges for Prevention and Early Intervention for Personality Disorder","volume":"37","author":"Chanen","year":"2021","journal-title":"Curr. 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