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Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.

ABSTRACT: 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.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).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?

SUBMITTER: Hirschtritt ME

PROVIDER: S-EPMC4446055 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.

Hirschtritt Matthew E ME Lee Paul C PC Pauls David L DL Dion Yves Y Grados Marco A MA Illmann Cornelia C King Robert A RA Sandor Paul P McMahon William M WM Lyon Gholson J GJ Cath Danielle C DC Kurlan Roger R Robertson Mary M MM Osiecki Lisa L Scharf Jeremiah M JM Mathews Carol A CA

JAMA psychiatry 20150401 4

<h4>Importance</h4>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.<h4>Objective</h4>To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric como ...[more]

PMID: 25671412

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Project description:BackgroundTourette syndrome (TS) is often found comorbid with other neurodevelopmental disorders across the impulsivity-compulsivity spectrum, with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) as most prevalent. This points to the possibility of a common etiological thread along an impulsivity-compulsivity continuum.MethodsInvestigating the shared genetic basis across TS, ADHD, ASD, and OCD, we undertook an evaluation of cross-disorder genetic architecture and systematic meta-analysis, integrating summary statistics from the latest genome-wide association studies (93,294 individuals, 6,788,510 markers).ResultsAs previously identified, a common unifying factor connects TS, ADHD, and ASD, while TS and OCD show the highest genetic correlation in pairwise testing among these disorders. Thanks to a more homogeneous set of disorders and a targeted approach that is guided by genetic correlations, we were able to identify multiple novel hits and regions that seem to play a pleiotropic role for the specific disorders analyzed here and could not be identified through previous studies. In the TS-ADHD-ASD genome-wide association study single nucleotide polymorphism-based and gene-based meta-analysis, we uncovered 13 genome-wide significant regions that host single nucleotide polymorphisms with a high posterior probability for association with all three studied disorders (m-value > 0.9), 11 of which were not identified in previous cross-disorder analysis. In contrast, we also identified two additional pleiotropic regions in the TS-OCD meta-analysis. Through conditional analysis, we highlighted genes and genetic regions that play a specific role in a TS-ADHD-ASD genetic factor versus TS-OCD. Cross-disorder tissue specificity analysis implicated the hypothalamus-pituitary-adrenal gland axis in TS-ADHD-ASD.ConclusionsOur work underlines the value of redefining the framework for research across traditional diagnostic categories.

Project description:Cardiometabolic disorders have known inflammatory implications, and peripheral measures of inflammation and cardiometabolic disorders are common in persons with psychotic disorders. Inflammatory signatures are also related to neurobiological and behavioral changes in psychosis. Relationships between systemic inflammation and cardiometabolic genetic risk in persons with psychosis have not been examined. Thirteen peripheral inflammatory markers and genome-wide genotyping were assessed in 122 participants (n = 86 psychosis, n = 36 healthy controls) of European ancestry. Cluster analyses of inflammatory markers classified higher and lower inflammation subgroups. Single-trait genetic risk scores (GRS) were constructed for each participant using previously reported GWAS summary statistics for the following traits: schizophrenia, bipolar disorder, major depressive disorder, coronary artery disease, type-2 diabetes, low-density lipoprotein, high-density lipoprotein, triglycerides, and waist-to-hip ratio. Genetic correlations across traits were quantified. Principal component (PC) analysis of the cardiometabolic GRSs generated six PC loadings used in regression models to examine associations with inflammation markers. Functional module discovery explored biological mechanisms of the inflammation association of cardiometabolic GRS genes. A subgroup of 38% persons with psychotic disorders was characterized with higher inflammation status. These higher inflammation individuals had lower BACS scores (p = 0.038) compared to those with lower inflammation. The first PC of the cardiometabolic GRS matrix was related to higher inflammation status in persons with psychotic disorders (OR = 2.037, p = 0.001). Two of eight modules within the functional interaction network of cardiometabolic GRS genes were enriched for immune processes. Cardiometabolic genetic risk may predispose some individuals with psychosis to elevated inflammation which adversely impacts cognition associated with illness.

Project description:ObjectiveIt is not clear why psychiatric disorders are more prevalent in the functional somatic syndromes than other general medical illnesses. This study assessed the correlates of psychiatric disorders in 3 functional syndromes and 3 general medical illnesses in a population-based sample.MethodsThe Lifelines cohort study included 122,366 adults with relevant data for 6 self-reported conditions: irritable bowel syndrome (IBS), fibromyalgia, chronic fatigue syndrome (CFS), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and diabetes. For each condition the proportion with a DSM-IV psychiatric disorder was assessed. In a cross-sectional design, logistic regression identified at baseline the variables most closely associated with current psychiatric disorder in participants with a pre-existing medical or functional condition. In a separate analysis the prevalence of psychiatric disorder prior to onset of these conditions was assessed. This was a longitudinal study with psychiatric disorder assessed at baseline in participants who subsequently developed a general medical or functional condition between baseline and follow-up.ResultsThe prevalence of psychiatric disorder was higher (17-27%) in the functional somatic syndromes than the general medical illnesses (10.4-11.7%). The variables closely associated with psychiatric disorder were similar in the functional syndromes and general medical illnesses: stressful life events, chronic personal health difficulties, neuroticism, poor perception of general health, impairment of function due to physical illness and reported previous (lifetime) psychiatric disorder. The prevalence of psychiatric disorder prior to development of these disorder was similar to that of established disorders.ConclusionDespite the difference in prevalence, the correlates of psychiatric disorders were similar in functional and general medical disorders and included predisposing and environmental factors. The increased rate of psychiatric disorder in functional somatic syndromes appears to be evident before onset of the syndrome.

Dataset Information

Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.

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Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.

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