{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:29:59Z","timestamp":1787495399097,"version":"build-2736575974"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007857","name":"Intellectual and Developmental Disabilities Research Center","doi-asserted-by":"publisher","award":["U54HD079125"],"award-info":[{"award-number":["U54HD079125"]}],"id":[{"id":"10.13039\/100007857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001860"],"award-info":[{"award-number":["UL1TR001860"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>\n                    Individuals with the fragile X premutation report symptoms of chronic pain from multiple systems, have increased incidence of comorbid conditions where pain is a prominent feature, and pathophysiology that supports disrupted pain regulation, inflammation, and energy imbalance. Less is known about how pain manifests for the subpopulation of carriers that develop the motor and cognitive changes of fragile X-associated tremor and ataxia syndrome (FXTAS), and how pain may differ between men and women. We gathered data collected from 104 males and females with FXTAS related to chronic pain, comorbid conditions related to pain, and medications used for pain control to further explore the types of pain experienced and to better characterize how individuals with the fragile X premutation experience pain sensation across genders. We found that women experience significantly more pain symptoms than men, particularly allodynia (20 vs. 2.0%,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.008), peripheral neuropathy pain (43.9 vs. 25.4%,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.0488), migraine (43.9 vs. 14.5%,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.0008), fibromyalgia (26.8 vs. 0%,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.0071) and back pain (48.5 vs. 23.4%,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.008). We found onset of peripheral neuropathy predicts the onset of ataxia (\u03b2 = 0.63 \u00b1 0.25,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.019) and tremor (\u03b2 = 0.56 \u00b1 0.17,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.004) across gender. Women also report significantly more anxiety (82.9 vs. 39.7%,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.001), which has implications for ideal pain treatment. These pain symptoms need to be recognized in the medical history and treated appropriately, with consideration for overlapping comorbidities.\n                  <\/jats:p>","DOI":"10.3389\/fpsyt.2021.762915","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T02:43:51Z","timestamp":1642646631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Increased Pain Symptomatology Among Females vs. Males With Fragile X-Associated Tremor\/Ataxia Syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Devon","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellery","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Ponzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingratana A.","family":"McLennan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi J.","family":"Hagerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/nrneurol.2016.82","article-title":"Fragile X-associated tremor\/ataxia syndrome\u2014features, mechanisms and management","volume":"12","author":"Hagerman","year":"2016","journal-title":"Nat Rev Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1866-1955-6-31","article-title":"Emerging topics in FXTAS","volume":"6","author":"Hall","year":"2014","journal-title":"J Neurodev Disord."},{"key":"B3","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1001\/jama.291.4.460","article-title":"Penetrance of the Fragile X\u2013Associated Tremor\/Ataxia Syndrome in a Premutation Carrier Population","volume":"291","author":"Jacquemont","year":"2004","journal-title":"JAMA."},{"key":"B4","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1002\/mdc3.13084","article-title":"Women with fragile x\u2013associated tremor\/ataxia syndrome","volume":"7","author":"Schneider","year":"2020","journal-title":"Mov Disord Clin Pract"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1212\/NXG.0000000000000045","article-title":"X-inactivation in the clinical phenotype of fragile X premutation carrier sisters","volume":"2","author":"Hall","year":"2016","journal-title":"Neurol Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1002\/ajmg.a.35569","article-title":"Immune-mediated disorders among women carriers of fragile X premutation alleles","author":"Winarni","year":"2012","journal-title":"Am J Med Genet Part A"},{"key":"B7","doi-asserted-by":"publisher","first-page":"577248","DOI":"10.3389\/fmolb.2020.577246","article-title":"Differential progression of motor dysfunction between male and female fragile X premutation carriers reveals novel aspects of sex-specific neural involvement","volume":"7","author":"Loesch","year":"2021","journal-title":"Front Mol Biosci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1002\/ajmg.a.31920","article-title":"Neuropathy as a presenting feature in fragile X-associated tremor\/ataxia syndrome","author":"Hagerman","year":"2007","journal-title":"Am J Med Genet Part A"},{"key":"B9","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3390\/biomedicines8050136","article-title":"Ataxia as the major manifestation of fragile X-associated tremor\/ataxia syndrome (FXTAS): case series","volume":"8","author":"Salcedo-Arellano","year":"2020","journal-title":"Biomedicines"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1093\/rheumatology\/ker273","article-title":"Fibromyalgia in fragile X mental retardation 1 gene premutation carriers","volume":"50","author":"Leehey","year":"2011","journal-title":"Rheumatology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1002\/ajmg.a.32060","article-title":"Expanded clinical phenotype of women with theFMR1 premutation","author":"Coffey","year":"2008","journal-title":"Am J Med Genet Part A"},{"key":"B12","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.rbre.2017.01.005","article-title":"do E, Berssaneti AA, Matsutani LA, Yuan SLK. 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