{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:33:25Z","timestamp":1792265605876,"version":"4.4.0"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001262","name":"Baily Thomas Charitable Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001262","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000311","name":"Tuberous Sclerosis Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000311","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The association between attention\u2010deficit\/hyperactivity disorder (ADHD) and tuberous sclerosis complex (TSC) is widely reported, with support for the role of epilepsy, yet the mechanisms underlying the association across development are unclear. The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of TSC. In Phase 1 of the study, baseline measures of epilepsy, cortical tuber load, and mutation were obtained with 125 children ages 0\u201316\u2009years. In Phase 2, at an average of 8\u2009years later, ADHD symptoms were measured for 81 of the participants. Structural equation modeling revealed an indirect pathway from genetic mutation, to cortical tuber load, to epileptic spasm severity in infancy, to ADHD symptoms in middle childhood and adolescence, in addition to a pathway linking current seizure severity to ADHD symptoms. Findings were retained when intelligence quotient (IQ) was entered as a correlated factor. The findings support a cascading developmental pathway to ADHD symptoms mediated by early\u2010onset and severe epilepsy in the first 2\u2009years of life. This warrants detailed investigation of seizure characteristics and cognitive and behavioral sequelae associated with ADHD from early in life, to further the understanding of the association between ADHD and early\u2010onset epilepsy across syndromic and non\u2010syndromic populations.<\/jats:p>","DOI":"10.1111\/epi.17507","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T10:25:04Z","timestamp":1673519104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Epilepsy severity mediates association between mutation type and ADHD symptoms in tuberous sclerosis complex"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-9547","authenticated-orcid":false,"given":"Charlotte","family":"Tye","sequence":"first","affiliation":[{"name":"Department of Child &amp; Adolescent Psychiatry, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-481X","authenticated-orcid":false,"given":"Fiona S.","family":"McEwen","sequence":"additional","affiliation":[{"name":"Department of Child &amp; Adolescent Psychiatry, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-9449","authenticated-orcid":false,"given":"Holan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Child &amp; Adolescent Psychiatry, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-6329","authenticated-orcid":false,"given":"Emma","family":"Woodhouse","sequence":"additional","affiliation":[{"name":"Department of Child &amp; Adolescent Psychiatry, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7775-8272","authenticated-orcid":false,"given":"Lisa","family":"Underwood","sequence":"additional","affiliation":[{"name":"Department of Child &amp; Adolescent Psychiatry, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-3565","authenticated-orcid":false,"given":"Elizabeth","family":"Shephard","sequence":"additional","affiliation":[{"name":"Department of Child &amp; Adolescent Psychiatry, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9914-8958","authenticated-orcid":false,"given":"Edward D.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Psychology, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9891-7612","authenticated-orcid":false,"given":"Fintan","family":"Sheerin","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology Oxford University Hospital NHS Foundation Trust  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Radiology, Addenbrooke's Hospital Cambridge University Hospitals NHS Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juul","family":"Steenbruggen","sequence":"additional","affiliation":[{"name":"Department of Child &amp; 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