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Neurology. 2016 Aug 2;87(5):497-504. doi: 10.1212/WNL.0000000000002910. Epub 2016 Jul 1.

Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.

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From the Department of Psychiatry (M.E.H., S.M.D., K.L.D.), University of California, San Francisco; Psychiatric and Neurodevelopmental Genetics Unit (C.I., L.O., D.L.P., E.G., D.Y., J.M.S.), Center for Human Genetics Research, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry and Behavioral Sciences (M.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Psychiatry (P.S.), University of Toronto and University Health Network, Youthdale Treatment Centers; Department of Psychiatry (Y.D.), University of Montreal, Canada; Yale Child Study Center (R.A.K.), Yale University School of Medicine, New Haven, CT; The Feinstein Institute for Medical Research (C.L.B.), North Shore Long Island Jewish Health System, Manhasset, NY; Faculty of Social and Behavioural Sciences (D.C.C.), Utrecht University and Altrecht Academic Anxiety Center, Utrecht, the Netherlands; Stanley Institute for Cognitive Genomics (G.J.L.), Cold Spring Harbor Laboratory, NY; School of Education (L.M.M.), American University, Washington, DC; Department of Psychiatry (W.M.M.), University of Utah, Salt Lake City; Department of Behavioral Health (P.C.L.), Tripler Army Medical Center, Honolulu, HI; Division of Cognitive and Behavioral Neurology (J.M.S.), Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Neurology (J.M.S.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Department of Psychiatry (C.A.M.), University of Florida, Gainesville.



To identify heritable symptom-based subtypes of Tourette syndrome (TS).


Forty-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.


A 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)).


Expanding 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.

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