Genetic factors in substance abuse based on studies of Tourette Syndrome and ADHD probands and relatives. I. Drug abuse

Department of Medical Genetics, City of Hope Medical Center, Duarte, CA 91010.
Drug and Alcohol Dependence (Impact Factor: 3.28). 04/1994; 35(1):17-24. DOI: 10.1016/0376-8716(94)90105-8
Source: PubMed

ABSTRACT Prior studies have suggested childhood attention deficit hyperactivity disorder (ADHD) as a risk factor for alcohol abuse in adults. Gilles de la Tourette Syndrome, a hereditary tic and impulse disorder, is clinically and genetically similar to ADHD. To examine the hypothesis that individuals carrying the Gts gene are at increased risk to develop alcohol use problems, the same TS (Tourette Syndrome) and ADHD probands, relatives and controls used in the prior study of drug abuse were also studied using a structured questionnaire based on the Diagnostic Interview Schedule and the MAST test. The frequency of a positive response to any of 16 different questions concerning alcohol abuse showed a highly significant increase with increased genetic loading for Gts and ADHD genes. The percentage of more than one positive response in TS probands was markedly influenced by the presence of comorbid ADHD, discipline, obsessive-compulsive or drug abuse problems. Comorbid drug abuse problems were the best predictor of alcohol abuse problems. These results suggest that the genes responsible for TS and ADHD play an important role in alcohol abuse/dependence as well as drug abuse/dependence. One of the elements common to all of these disorders may be mutant genes affecting serotonin metabolism.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The comorbidity of tic disorders (TD) and obsessive-compulsive disorder (OCD) has long been recognized in the clinical literature and appears to be bidirectional, affecting 20-60% of individuals with each disorder. Coffey et al. (1998) found that adults with TD+OCD had a more severe comorbidity profile than adults with OCD or TD alone. This exploratory study in children attempts to evaluate whether heightened diagnostic severity, increased comorbidity load, and lower functioning is more commonplace in youth with TD+OCD in comparison to either syndrome alone. Participants were 306 children (seeking clinical evaluation) with TD, OCD, or TD+OCD. Assessment consisted of a diagnostic battery (including structured diagnostic interviews and standardized parent-report inventories) to evaluate diagnostic severity, comorbid psychopathology, behavioral and emotional correlates, and general psychosocial functioning. Data from this study sample were not supportive of the premise that youth with both a tic disorder and OCD present with elevated diagnostic severity, higher risk-for or intensity-of comorbidity, increased likelihood of externalizing/internalizing symptomatology, or lower broad-based adaptive functioning. The OCD group had elevated rates of comorbid anxiety disorders and attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) were more prevalent among youth in the TD group. The three groups also differed on key demographic variables. Our findings suggest that, in contrast to adults, TD+OCD in children and adolescents does not represent a more severe condition than either disorder alone on the basis of diagnostic comorbidity, symptom severity, or functional impairment.
    Psychiatry Research 07/2010; 178(2):317-22. DOI:10.1016/j.psychres.2009.11.013 · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies have demonstrated a significant positive correlation between attention deficit hyperactivity disorder (ADHD), a common childhood behavioural disorder, and the development of alcoholism or drug abuse in adulthood. Recent investigations have suggested that these disorders may be genetically determined Dysfunction of the dopamine D2 receptor gene (DRD2) has been identified as a possible genetic variation responsible for alterations in behaviour. Ongoing studies have indicated that variants of other dopamine receptor subtypes, such as D3, and serotonin (5-hydroxytryptamine; 5-HT) metabolism may also be implicated in impulsive, compulsive and addictive behaviours. Such alterations in the genetic make-up result in functional deficiency of meso limbic and frontal lobe dopamine metabolism These findings provide a sound pharmacological basis for the treatment of ADHD with stimulants, such as methylphenidate and dexamphetamine (dextroamphetamine), and indicate that dopamine agonists may prove to be useful in the treatment of other impulsive, compulsive and addictive behaviours.
    CNS Drugs 01/1994; 1(1):1-5. DOI:10.2165/00023210-199401010-00001 · 4.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tourette syndrome (TS) is a common, neuropsychiatric disorder which has many similarities to attention deficit hyperactivity disorder (ADHD). TS probands have a high frequency of a variety of behavioral disorders including depression. The depression may be due to a pleiotrophic effect of the Gts 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-III-R 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 Gts 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-proband TS relatives versus non-TS relatives, indicating the association of depression with Gts genes was not due to ascertainment bias or the inappropriate choice of controls. Multiple linear regression analysis indicated that obsessive-compulsive 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 Gts and ADHD genes play a major role in depression.
    American Journal of Medical Genetics 04/1995; 60(2):111-21. DOI:10.1002/ajmg.1320600206 · 3.23 Impact Factor