S Evelyn Stewart1, Cornelia Illmann1, Daniel A Geller1, James F Leckman1, Robert King1, David L Pauls2. 1. Drs. Stewart, Illmann, Geller, and Pauls are with the Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston; Drs. Leckman and King are with the Child Study Center, Yale University School of Medicine, New Haven, CT. 2. Drs. Stewart, Illmann, Geller, and Pauls are with the Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston; Drs. Leckman and King are with the Child Study Center, Yale University School of Medicine, New Haven, CT.. Electronic address: dpauls@partners.org.
Abstract
OBJECTIVE: Although attention-deficit/hyperactivity disorder (ADHD) is frequently comorbid with Tourette's disorder (TD), it is unclear whether they have a common genetic etiology. Familial relationships between DSM-IV ADHD and TD are studied in TD+ADHD, TD-only (TD-ADHD), ADHD-only (ADHD-TD), and control groups. METHOD: Case-control, direct-interview family study of 692 relatives of 75 TD+ADHD, 74 TD-only, 41 ADHD-only, and 49 control probands collected between 1999 and 2004. Age-corrected prevalence rates, odds ratios, and predictors of TD, ADHD, and OCD among relatives are estimated from blinded best-estimate diagnoses using survival Kaplan-Meier and generalized estimating equation regression analyses. RESULTS: In relatives of the TD-only group, although ADHD exceeded control rates (p=.03), ADHD-TD (p=.51) rates were not increased. In the ADHD-only group, TD was increased (p=.004) but TD-ADHD rates were not increased (p=.18). Comorbid ADHD+TD diagnoses in relatives were elevated in all case groups (p<or=.03). TD in relatives predicted comorbid ADHD (p<.001), and ADHD in relatives predicted comorbid TD (p<.001). OCD in relatives predicted both ADHD (p=.002) and TD (p<.001) in relatives. CONCLUSIONS: TD and ADHD are not alternate phenotypes of a single underlying genetic cause. There is an increased risk of comorbid ADHD and TD in affected families, possibly reflecting some overlapping neurobiology or pathophysiology.
OBJECTIVE: Although attention-deficit/hyperactivity disorder (ADHD) is frequently comorbid with Tourette's disorder (TD), it is unclear whether they have a common genetic etiology. Familial relationships between DSM-IV ADHD and TD are studied in TD+ADHD, TD-only (TD-ADHD), ADHD-only (ADHD-TD), and control groups. METHOD: Case-control, direct-interview family study of 692 relatives of 75 TD+ADHD, 74 TD-only, 41 ADHD-only, and 49 control probands collected between 1999 and 2004. Age-corrected prevalence rates, odds ratios, and predictors of TD, ADHD, and OCD among relatives are estimated from blinded best-estimate diagnoses using survival Kaplan-Meier and generalized estimating equation regression analyses. RESULTS: In relatives of the TD-only group, although ADHD exceeded control rates (p=.03), ADHD-TD (p=.51) rates were not increased. In the ADHD-only group, TD was increased (p=.004) but TD-ADHD rates were not increased (p=.18). Comorbid ADHD+TD diagnoses in relatives were elevated in all case groups (p<or=.03). TD in relatives predicted comorbid ADHD (p<.001), and ADHD in relatives predicted comorbid TD (p<.001). OCD in relatives predicted both ADHD (p=.002) and TD (p<.001) in relatives. CONCLUSIONS: TD and ADHD are not alternate phenotypes of a single underlying genetic cause. There is an increased risk of comorbid ADHD and TD in affected families, possibly reflecting some overlapping neurobiology or pathophysiology.
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