Hirschtritt ME, Lee PC, Pauls DL, Dion Y, Grados MA, Illmann C, King RA,
Sandor P, McMahon WM, Lyon GJ, Cath DC, Kurlan R, Robertson MM, Osiecki L, Scharf
JM, Mathews CA; Tourette Syndrome Association International Consortium for
Genetics. Lifetime prevalence, age of risk, and genetic relationships of comorbid
psychiatric disorders in Tourette syndrome. JAMA Psychiatry. 2015
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.
To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS.
DESIGN, SETTING, AND PARTICIPANTS:
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).
MAIN OUTCOMES AND MEASURES:
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.
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 AND RELEVANCE:
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.
From the manuscript:
From the manuscript:
The heritability estimates confirm previous research showing that TS, OCD, and ADHD are highly genetically related. However, for the first time, we also provide evidence of a strong genetic relationship between these TS-related phenotypes and mood, anxiety, and DBD. Of particular interest, our analyses suggest that the observed genetic correlations between TS and these disorders are better accounted for by an underlying genetic relationship with ADHD and, in the case of mood disorders, by an underlying genetic relationship with both ADHD and OCD. In non-TS samples, there is considerable evidence to support shared genetic variance between ADHD and DBD, and some data to support a shared genetic diathesis underlying ADHD and major depressive disorder. Genetic relationships between OCD and mood disorders have not previously been examined. Our findings are in line with a previous study that found no increased rates of ADHD or other non-OCD disorders such as anxiety, affective, substance abuse and psychotic disorders, among parents of probands with TS compared to controls, suggesting that these disorders segregate independently from TS. Our findings that parental history of ADHD predicts psychiatric disorder burden in TS-affected offspring, independent of parental history of TS and OCD, provides additional support for the observed genetic relationships between psychiatric disorders and ADHD...
This study provides important new data regarding the prevalence, predictors, and ages of highest risk for psychiatric illness among individuals affected with TS, as well as for the first time formally evaluating the etiological relationships between disorders other than OCD and ADHD. The key clinical findings, that mood, anxiety, and DBD are very common among TS-affected individuals, tend to begin early in life, and are highly associated with comorbid OCD and ADHD, are of direct and immediate relevance for practitioners. The genetic analyses advance our understanding of the etiological relationships between TS and other psychiatric disorders, and provide a framework for future studies aimed at better understanding the biology of these complex, inter-related syndromes.
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