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The depression may be due to a pleiotrophic effect of the <jats:italic>Gts<\/jats:italic> genes, proband ascertainment bias, or a result of coping with the chronic tics. To distinguish between these hypotheses we examined the responses to 17 Diagnostic Interview Schedule questions to evaluate the 9 DSM\u2010III\u2010R criteria for major depressive episode in 1,080 adults consisting of TS and ADHD probands, their relatives and controls. Using a Bonferonni corrected p there was a significant progressive increase in 16 of 17 depressive symptoms and for a life time history of a major depressive episode in groups with increased genetic loading for <jats:italic>Gts<\/jats:italic> genes. Similar trends were seen in the small number of ADHD probands and their relatives. There was also a significant increase for these variables in non\u2010proband TS relatives versus non\u2010TS relatives, indicating the association of depression with <jats:italic>Gts<\/jats:italic> genes was not due to ascertainment bias or the inappropriate choice of controls. Multiple linear regression analysis indicated that obsessive\u2010compulsive behaviors, sex, ADHD, drug abuse, and age all showed a more significant effect on depressive symptoms than the number of tics. The presence or absence of TS in the relatives had a much greater effect on risk for depression than the presence or absence of an episode of major depression in the proband. These results are consistent with the hypothesis that <jats:italic>Gts<\/jats:italic> and <jats:italic>ADHD<\/jats:italic> genes play a major role in depression. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.1320600206","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T18:17:45Z","timestamp":1118513865000},"page":"111-121","source":"Crossref","is-referenced-by-count":20,"title":["Role of genetic factors in depression based on studies of Tourette syndrome and ADHD probands and their relatives"],"prefix":"10.1002","volume":"60","author":[{"given":"David E.","family":"Comings","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,3]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.145.12.1582"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.2307\/3001775"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1246632"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(84)80012-9"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/326289a0"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0193-49"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(86)90030-0"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.144.3.330"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199007000-00004"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1991.01810310051009"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1992.01820090056010"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.150.12.1792"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.149.11.1473"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/002221948501801008"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00709726"},{"key":"e_1_2_1_17_1","volume-title":"The Role of Serotonin in Psychiatric Disorders","author":"Brown S.\u2010L","year":"1990"},{"key":"e_1_2_1_18_1","first-page":"529","article-title":"Depression in children referred to an educational diagnostic center: Diagnosis and treatment and analysis of criteria and literature review","volume":"38","author":"Brumback RA","year":"1977","journal-title":"Dis Nerv Syst"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.137.4.445"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199403000-00012"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.2307\/3001616"},{"key":"e_1_2_1_22_1","first-page":"804","article-title":"A controlled study of Tourette syndrome. 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