Familial Clustering of Tic Disorders and Obsessive-Compulsive Disorder

Browne, Heidi A.; Hansen, Stefan N.; Buxbaum, Joseph D.; Gair, Shannon L.; Nissen, Judith Becker; Nikolajsen, Kathrine Hesselberg; Schendel, Diana; Reichenberg, Abraham; Parner, Erik Thorlund; Grice, Dorothy E.

doi:10.1001/jamapsychiatry.2014.2656

Cited by 80 publications

(56 citation statements)

References 67 publications

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“…In addition, clinical studies reported several immunological changes in the periphery (e.g., dysgammaglobulinemia, decreased number of T regulatory cells, increased antibody response to pathogens) which point to chronically hyperactive innate and adaptive mechanisms 39 . [49][50][51] .…”

Section: Endogenous Opioidsmentioning

confidence: 99%

Gilles de la Tourette syndrome

Robertson

Eapen

Singer

et al. 2017

Nat Rev Dis Primers

296

244

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The unstructured abstract of 200 words maximum should summarize the main points of the article. All information mentioned in the abstract must be addressed somewhere in the main article. The abstract should not contain references or display item citations. Gilles de la Tourette Syndrome (GTS), a reasonably common disorder, has had a long, tortuous and somewhat controversial history. First and well described in the 18th century 1,2 , the main features of GTS have, however, remained fairly constant. The core diagnostic features are multiple motor and one or more vocal (phonic) tics lasting for over a year. In addition, almost pathognomic, but not necessary, features described in the early documentations include coprolalia (involuntary, inappropriate swearing), and echophenomena (copying behaviours), as well as many co-morbidities and psychopathologies 3 . Introduction [suggested 500 words, is 544 words -8 refs] Mary Robertson Thoughts for Mary -Your word count when combining sections 1 and 2 is 1001 (1000 limit)-so OKGTS was originally described in France and the majority of early literature came from and standardised schedules such as diagnostic confidence, measurement of severity, QoL, and assessment of both co-morbidities and co-existent psychopathologies are currently available.Large international collaborative consortia are engaged in studies exploring aetiological factors in particular, and some international treatment studies are also underway. Perhaps as a result of earlier small patient numbers, the treatment trials have given good clues to management, but unsurprisingly systematic reviews and meta-analyses have been hampered, giving disappointing, if not unexpected, results. Intriguingly medications from the typical NRDP -Gilles de la Tourette Syndrome 3 antipsychotic family including haloperidol, which first had documented success in 1961 6,7 are still being used, although successive generations of "atypicals" are currently more in vogue,as are medications such as alpha-2-adrenergic agonists. Interestingly, haloperidol remains the only medication prescribed on licence in many parts of the world. In contrast to disorders such as ADHD, in which it is clear which treatments work and which do not require further study 8 , a variety of treatment studies in GTS are still being undertaken, including using other medications (trying to improve efficacy and reduce side effects), behavioural therapies, deep brain stimulation (for refractory cases), and other more "alternative" methods such as "orthotics" (teeth braces). The GTS community has to first agree on how common GTS is and then seek funding for research in the areas of major importance.2. Epidemiology [suggested 500 words, is 444 words, 6 additional refs] Mary Robertson GTS was for many years thought to be not only very rare, but a bizarre curiosity, with sporadic case reports peppering the literature. The belief that GTS was uncommon at the very least was held by many until Comings 9 controversially suggested that GTS occurred in between 0.66% and...

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Section: Endogenous Opioidsmentioning

confidence: 99%

Gilles de la Tourette syndrome

Robertson

Eapen

Singer

et al. 2017

Nat Rev Dis Primers

296

244

View full text Add to dashboard Cite

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“…Averaged over all birth years, the sibling RRR of OCD was 4.9 and the sibling RRR for tic disorders (TD; including TS and CT) was 18.6. When examining risk to offspring of affected parents even greater risk was documented with a parent-offspring RRR for OCD at 6.3 and for TD at 61.0 96 . These large, unbiased studies have thus supported the familial nature of OCD and rendered strong yet indirect evidence indicative of a substantial genetic contribution to this disorder.…”

Section: Familial Recurrence Risk In Ocd and Related Disordersmentioning

confidence: 99%

Genetics of Obsessive-Compulsive Disorder and Related Disorders

Browne

Gair

Scharf

et al. 2014

Psychiatric Clinics of North America

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Synopsis Twin and family studies support a significant genetic contribution to obsessive-compulsive disorder (OCD) and related disorders such as chronic tic disorders, trichotillomania, skin picking disorder, body dysmorphic disorder, and hoarding disorder. Recently, population-based studies and novel laboratory-based methods have confirmed substantial heritability in OCD. Genome-wide association studies and candidate gene association studies have provided information on specific genes that may be involved in the pathobiology of OCD and also of related disorders, particularly chronic tic disorders, though these genes each contribute only a small portion of the total genetic risk and a substantial portion of the specific genetic risk profile in OCD is still unknown. Nevertheless, there are some examples of genes for which perturbations produce OCD-like phenotypes in animal model systems, allowing a laboratory platform for investigating the pathobiology of --- and new treatments for --- OCD and related disorders. Future work promises to continue to clarify the specific genes involved in risk for OCD as well as their interaction with environmental variables.

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“…A fundamental obstacle to identifying novel therapeutic targets is a limited understanding of underlying pathophysiology. There is widespread agreement that genetics plays a significant role in TD etiology based on twin and family studies (Browne et al, 2015; Mataix-Cols et al, 2015; Pauls et al, 1981, 1991; Price et al, 1985). To date, non-parametric linkage analyses (The Tourette Syndrome Association International Consortium for Genetics, 1999, 2007) and a genome-wide association study (Scharf et al, 2013) have not yet led to reproducible, statistically significant findings.…”

Section: Introductionmentioning

confidence: 99%

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

Willsey

Fernandez

et al. 2017

Neuron

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161

187

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SUMMARY Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases.

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Familial Clustering of Tic Disorders and Obsessive-Compulsive Disorder

Cited by 80 publications

References 67 publications

Gilles de la Tourette syndrome

Gilles de la Tourette syndrome

Genetics of Obsessive-Compulsive Disorder and Related Disorders

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

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