Effectiveness of a web-based protocol for the screening and phenotyping of individuals with tourette syndrome for genetic studies
ABSTRACT Genome-wide association studies (GWAS) and other emerging technologies offer great promise for the identification of genetic risk factors for complex psychiatric disorders, yet such studies are constrained by the need for large sample sizes. Web-based collection offers a relatively untapped resource for increasing participant recruitment. Therefore, we developed and implemented a novel web-based screening and phenotyping protocol for genetic studies of Tourette syndrome (TS), a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. Participants were recruited over a 13-month period through the membership of the Tourette Syndrome Association (TSA; n = 28,878). Of the TSA members contacted, 4.3% (1,242) initiated the questionnaire, and 79.5% (987) of these were enrollment eligible. 63.9% (631) of enrolled participants completed the study by submitting phenotypic data and blood specimens. Age was the only variable that predicted study completion; children and young adults were significantly less likely to be study completers than adults 26 and older. Compared to a clinic-based study conducted over the same time period, the web-based method yielded a 60% larger sample. Web-based participants were older and more often female; otherwise, the sample characteristics did not differ significantly. TS diagnoses based on the web-screen demonstrated 100% accuracy compared to those derived from in-depth clinical interviews. Our results suggest that a web-based approach is effective for increasing the sample size for genetic studies of a relatively rare disorder and that our web-based screen is valid for diagnosing TS. Findings from this study should aid in the development of web-based protocols for other disorders. © 2012 Wiley Periodicals, Inc.
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ABSTRACT: Collecting phenotypic data necessary for genetic analyses of neuropsychiatric disorders is time consuming and costly. Development of web-based phenotype assessments would greatly improve the efficiency and cost-effectiveness of genetic research. However, evaluating the reliability of this approach compared to standard, in-depth clinical interviews is essential. The current study replicates and extends a preliminary report on the utility of a web-based screen for Tourette Syndrome (TS) and common comorbid diagnoses (obsessive compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD)). A subset of individuals who completed a web-based phenotyping assessment for a TS genetic study was invited to participate in semi-structured diagnostic clinical interviews. The data from these interviews were used to determine participants׳ diagnostic status for TS, OCD, and ADHD using best estimate procedures, which then served as the gold standard to compare diagnoses assigned using web-based screen data. The results show high rates of agreement for TS. Kappas for OCD and ADHD diagnoses were also high and together demonstrate the utility of this self-report data in comparison previous diagnoses from clinicians and dimensional assessment methods. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.Psychiatry Research 05/2015; 228(3). DOI:10.1016/j.psychres.2015.05.017 · 2.47 Impact Factor
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ABSTRACT: Streptococcal infection and basal ganglia inflammation are hypothesized to be involved in Tourette's syndrome (TS). There is a need for effective therapies for managing TS. We studied streptococcal infection and immunity in TS following immunomodulator (pidotimod) therapy. Blood samples from 58 patients with TS and 128 age-matched healthy controls enabled measurement of antistreptolysin O (ASO), T cells, natural killer (NK) cells, interleukin-6 (IL-6) and interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Forty-four patients with abnormal T cell numbers were divided into two groups and treated with pidotimod granules (pidotimod group, n = 20) or pidotimod plus dopaminergic receptor antagonists (combination group, n = 24). Yale Global Tic Severity Scale (YGTSS) scores and immunologic indices were assessed after treatment. An ASO >1:200 was found in 22.4 % of children with TS, 7.5 % of controls, and 38.9 % of children with both TS and attention deficit hyperactivity disorder (ADHD) compared to 15.0 % of children with TS alone (P < 0.05). Children with TS showed decreased CD3(+) and CD4(+) T cells, CD4(+)/CD8(+) ratio, IL-6 and IL-8, increased NKC and TNF-α (P < 0.05) as compared to controls. ASO-positive children with TS had lower CD4(+) T cells as compared to ASO-negative children with TS, and lower IL-6 and IL-8 levels as compared to controls (P < 0.05). After 8 weeks of pidotimod treatment, IL-8 was increased compared to either tiapride hydrochloride or haloperidol and pidotimod (P < 0.05). Streptococcal infection in TS patients is associated with immune and cytokine dysfunction, which can be potentially managed with immunomodulator therapy.Child s Nervous System 05/2015; 31(7). DOI:10.1007/s00381-015-2692-8 · 1.11 Impact Factor