title: Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.
abstract: OBJECTIVE
  Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (<200), and none has examined the ages of highest risk for each TS-associated comorbidity or their etiologic relationship to TS.
  
  
  OBJECTIVE
  To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS.
  
  
  METHODS
  Cross-sectional structured diagnostic interviews conducted between April 1, 1992, and December 31, 2008, of participants with TS (n = 1374) and TS-unaffected family members (n = 1142).
  
  
  METHODS
  Lifetime prevalence of comorbid DSM-IV-TR disorders, their heritabilities, ages of maximal risk, and associations with symptom severity, age at onset, and parental psychiatric history.
  
  
  RESULTS
  The lifetime prevalence of any psychiatric comorbidity among individuals with TS was 85.7%; 57.7% of the population had 2 or more psychiatric disorders. The mean (SD) number of lifetime comorbid diagnoses was 2.1 (1.6); the mean number was 0.9 (1.3) when obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) were excluded, and 72.1% of the individuals met the criteria for OCD or ADHD. Other disorders, including mood, anxiety, and disruptive behavior, each occurred in approximately 30% of the participants. The age of greatest risk for the onset of most comorbid psychiatric disorders was between 4 and 10 years, with the exception of eating and substance use disorders, which began in adolescence (interquartile range, 15-19 years for both). Tourette syndrome was associated with increased risk of anxiety (odds ratio [OR], 1.4; 95% CI, 1.0-1.9; P = .04) and decreased risk of substance use disorders (OR, 0.6; 95% CI, 0.3-0.9; P = .02) independent from comorbid OCD and ADHD; however, high rates of mood disorders among participants with TS (29.8%) may be accounted for by comorbid OCD (OR, 3.7; 95% CI, 2.9-4.8; P < .001). Parental history of ADHD was associated with a higher burden of non-OCD, non-ADHD comorbid psychiatric disorders (OR, 1.86; 95% CI, 1.32-2.61; P < .001). Genetic correlations between TS and mood (RhoG, 0.47), anxiety (RhoG, 0.35), and disruptive behavior disorders (RhoG, 0.48), may be accounted for by ADHD and, for mood disorders, by OCD.
  
  
  CONCLUSIONS
  This study is, to our knowledge, the most comprehensive of its kind. It confirms the belief that psychiatric comorbidities are common among individuals with TS, demonstrates that most comorbidities begin early in life, and indicates that certain comorbidities may be mediated by the presence of comorbid OCD or ADHD. In addition, genetic analyses suggest that some comorbidities may be more biologically related to OCD and/or ADHD rather than to TS.
authors: Program for Genetics and Epidemiology of Neuropsychiatric Symptoms, Department of Psychiatry, University of California, San Francisco.
authors: Matthew E
authors: ME
authors: Hirschtritt
authors: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Harvard Medical School, Massachusetts General Hospital, Boston.
authors: Paul C
authors: PC
authors: Lee
authors: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Harvard Medical School, Massachusetts General Hospital, Boston.
authors: David L
authors: DL
authors: Pauls
authors: Department of Psychiatry, University of Montreal, Montreal, Quebec, Canada.
authors: Yves
authors: Y
authors: Dion
authors: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Marco A
authors: MA
authors: Grados
authors: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Harvard Medical School, Massachusetts General Hospital, Boston.
authors: Cornelia
authors: C
authors: Illmann
authors: Yale Child Study Center, Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
authors: Robert A
authors: RA
authors: King
authors: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada7University Health Network, Toronto Western Research Institute, Toronto, Ontario, Canada8Youthdale Treatment Centers, Toronto, Ontario, Canada.
authors: Paul
authors: P
authors: Sandor
authors: Department of Psychiatry, University of Utah, Salt Lake City.
authors: William M
authors: WM
authors: McMahon
authors: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Woodbury, New York.
authors: Gholson J
authors: GJ
authors: Lyon
authors: Department of Clinical and Health Psychology, Utrecht University, Utrecht, the Netherlands12Altrecht Academic Anxiety Disorders Centre, Utrecht, the Netherlands.
authors: Danielle C
authors: DC
authors: Cath
authors: Atlantic Neuroscience Institute, Overlook Hospital, Summit, New Jersey.
authors: Roger
authors: R
authors: Kurlan
authors: University College London, London, England15St George's Hospital and Medical School, London, England16Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
authors: Mary M
authors: MM
authors: Robertson
authors: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Harvard Medical School, Massachusetts General Hospital, Boston.
authors: Lisa
authors: L
authors: Osiecki
authors: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Harvard Medical School, Massachusetts General Hospital, Boston17Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Techno.
authors: Jeremiah M
authors: JM
authors: Scharf
authors: Program for Genetics and Epidemiology of Neuropsychiatric Symptoms, Department of Psychiatry, University of California, San Francisco.
authors: Carol A
authors: CA
authors: Mathews
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D000367:Age Factors; D017668:Age of Onset; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology* / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D012307:Risk Factors; D005879:Tourette Syndrome / Q000453:epidemiology* / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult