August 02, 2016; 87 (5) Article
Social disinhibition is a heritable subphenotype of tics in Tourette syndrome
Matthew E. Hirschtritt, Sabrina M. Darrow, Cornelia Illmann, Lisa Osiecki, Marco Grados, Paul Sandor, Yves Dion, Robert A. King, David L. Pauls, Cathy L. Budman, Danielle C. Cath, Erica Greenberg, Gholson J. Lyon, Dongmei Yu, Lauren M. McGrath, William M. McMahon, Paul C. Lee, Kevin L. Delucchi, Jeremiah M. Scharf, Carol A. Mathews; On behalf of the Tourette Syndrome Association International Consortium for Genetics (TSAICG)
First published July 1, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002910
Matthew E. Hirschtritt
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.
Sabrina M. Darrow
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.
Cornelia Illmann
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.
Lisa Osiecki
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.
Marco Grados
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.
Paul Sandor
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.
Yves Dion
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.
Robert A. King
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.
David L. Pauls
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.
Cathy L. Budman
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.
Danielle C. Cath
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.
Erica Greenberg
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.
Gholson J. Lyon
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.
Dongmei Yu
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.
Lauren M. McGrath
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.
William M. McMahon
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.
Paul C. Lee
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.
Kevin L. Delucchi
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.
Jeremiah M. Scharf
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.
Carol A. Mathews
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.
Social disinhibition is a heritable subphenotype of tics in Tourette syndrome
Matthew E. Hirschtritt, Sabrina M. Darrow, Cornelia Illmann, Lisa Osiecki, Marco Grados, Paul Sandor, Yves Dion, Robert A. King, David L. Pauls, Cathy L. Budman, Danielle C. Cath, Erica Greenberg, Gholson J. Lyon, Dongmei Yu, Lauren M. McGrath, William M. McMahon, Paul C. Lee, Kevin L. Delucchi, Jeremiah M. Scharf, Carol A. Mathews
Neurology Aug 2016, 87 (5) 497-504; DOI: 10.1212/WNL.0000000000002910
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Abstract
Objective: To identify heritable symptom-based subtypes of Tourette syndrome (TS).
Methods: 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.
Results: 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).
Conclusions: 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.
GLOSSARY
- ADHD=
- attention-deficit/hyperactivity disorder;
- BIC=
- Bayesian information criterion;
- EFA=
- exploratory factor analysis;
- LCA=
- latent class analysis;
- OCD=
- obsessive-compulsive disorder;
- TS=
- Tourette syndrome
Footnotes
↵* These authors contributed equally to this work.
TSAICG coinvestigators are listed on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received October 20, 2015.
- Accepted in final form March 28, 2016.
- © 2016 American Academy of Neurology
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