The inheritance of Tourette Disorder: A review

Pauls, David L.; Fernandez, Thomas; Mathews, Carol A.; State, Matthew W.; Scharf, Jeremiah M.

doi:10.1016/j.jocrd.2014.06.003

Cited by 78 publications

(47 citation statements)

References 63 publications

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“…For the most part, many genetic findings in TS to date have not reached statistical significance or lack reproducibility. Studies now underway seek to utilize larger cohorts and high-throughput sequencing to garner support for specific genes and biological pathways in TS [123–125]. There is great hope that these new studies will accelerate progress in understanding TS so that we can improve the lives of those suffering from this debilitating disorder.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Tourette Syndrome: Bridging the Gap between Genetics and Biology

Richer

Fernandez

2015

Complex Psychiatry

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Tourette syndrome is a childhood neuropsychiatric disorder, which presents with disruptive motor and vocal tics. The disease also has a high comorbidity with obsessive-compulsive disorder and attention deficit hyperactivity disorder, which may further increase the distress experienced by patients. Current treatments act with varying efficacies in alleviating symptoms, as the underlying biology of the disease is not fully understood to provide precise therapeutic targets. Moreover, the genetic complexity of the disorder presents a substantial challenge to the identification of genetic alterations that contribute to the Tourette phenotype. Nevertheless, genetic studies have suggested involvement of dopaminergic, serotonergic, glutamatergic, and histaminergic pathways in the pathophysiology of at least some cases. In addition, genetic overlaps with other neuropsychiatric disorders may point toward a shared biology. The findings that are emerging from genetic studies will allow researchers to piece together the underlying components of the disease in the hopes that a deeper understanding of Tourette syndrome can lead to improved treatments for those affected by it.

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Section: Discussion and Future Directionsmentioning

confidence: 99%

Tourette Syndrome: Bridging the Gap between Genetics and Biology

Richer

Fernandez

2015

Complex Psychiatry

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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

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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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“…Tourette syndrome (TS) is highly heritable(1), yet etiological and phenotypic heterogeneity, including high rates of co-occurrence with attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD)(2–4), have hampered gene-finding efforts(5–7). Decreasing the observed phenotypic heterogeneity, for example using latent variable modeling, may improve efforts to clarify TS pathophysiology and genetic architecture by identifying more homogeneous TS-related endophenotypes(8).…”

Section: Introductionmentioning

confidence: 99%

Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome

Darrow

Hirschtritt

Davis

et al. 2017

AJP

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Objective Phenotypic heterogeneity in Tourette syndrome (TS) is partly due to complex genetic relationships between TS, obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. Method 3494 individuals recruited for genetic studies were assessed for TS, OCD, and ADHD symptoms. Symptom-level factor and latent class analyses were conducted in TS families and replicated in an independent sample. Classes were characterized by comorbidity rates and proportion of parents. Heritability and TS-, OCD-, and ADHD-associated polygenic load were estimated. Results We identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high (disinhibition factor= 0.35, SE=0.03, p= 4.2 ×10−34; symmetry factor= 0.39, SE=0.03, p= 7.2 ×10−31; symmetry class=0.38, SE=0.10, p=0.001). Mothers of TS probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a TS genome-wide association study (GWAS) were associated with symmetry (p= 0.02), while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were associated with disinhibition (p =0.03), while TS and ADHD risk scores were not. Conclusions We identified two heritable TS-related endophenotypes that cross traditional diagnostic boundaries. The symmetry phenotype correlated with TS polygenic load, and was present in otherwise “TS-unaffected” mothers, suggesting that this phenotype may reflect additional TS (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

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The inheritance of Tourette Disorder: A review

Cited by 78 publications

References 63 publications

Tourette Syndrome: Bridging the Gap between Genetics and Biology

Tourette Syndrome: Bridging the Gap between Genetics and Biology

Gilles de la Tourette syndrome

Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome

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