1. Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.
- Author
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Hirschtritt, Matthew E, Darrow, Sabrina M, Illmann, Cornelia, Osiecki, Lisa, Grados, Marco, Sandor, Paul, Dion, Yves, King, Robert A, Pauls, David L, Budman, Cathy L, Cath, Danielle C, Greenberg, Erica, Lyon, Gholson J, Yu, Dongmei, McGrath, Lauren M, McMahon, William M, Lee, Paul C, Delucchi, Kevin L, Scharf, Jeremiah M, Mathews, Carol A, and Tourette Syndrome Association International Consortium for Genetics (TSAICG)
- Subjects
Tourette Syndrome Association International Consortium for Genetics ,Humans ,Tourette Syndrome ,Tics ,Factor Analysis ,Statistical ,Social Behavior ,Obsessive-Compulsive Disorder ,Attention Deficit Disorder with Hyperactivity ,Age of Onset ,Comorbidity ,Phenotype ,Adolescent ,Adult ,Canada ,United States ,Netherlands ,Female ,Male ,Young Adult ,United Kingdom ,Inhibition ,Psychological ,Brain Disorders ,Neurodegenerative ,Neurosciences ,Genetics ,Serious Mental Illness ,Mental Health ,Mental health ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveTo identify heritable symptom-based subtypes of Tourette syndrome (TS).MethodsForty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined.ResultsA 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10(-18)).ConclusionsExpanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies.
- Published
- 2016