Pediatric Tourette syndrome: Insights from recent neuroimaging studies

Church, Jessica A.; Schlaggar, Bradley L.

doi:10.1016/j.jocrd.2014.04.002

Cited by 32 publications

(7 citation statements)

References 97 publications

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“…6,7 The largest studies were reported by Peterson and colleagues, with over 100 children and adults with TS and a similar number of control subjects. However, substantial questions remain about the structural anatomy of the brain in TS because methods and results have varied widely across studies, and because most studies were from small samples.…”

Section: Introductionmentioning

confidence: 99%

Brain structure in pediatric Tourette syndrome

et al. 2016

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Previous studies of brain structure in Tourette syndrome (TS) have produced mixed results, and most had modest sample sizes. In the present multi-center study, we used structural MRI to compare 103 children and adolescents with TS to a well-matched group of 103 children without tics. We applied voxel-based morphometry methods to test gray matter (GM) and white matter (WM) volume differences between diagnostic groups, accounting for MRI scanner and sequence, age, sex and total GM + WM volume. The TS group demonstrated lower WM volume bilaterally in orbital and medial prefrontal cortex, and greater GM volume in posterior thalamus, hypothalamus and midbrain. These results demonstrate evidence for abnormal brain structure in children and youth with TS, consistent with and extending previous findings, and they point to new target regions and avenues of study in TS. For example, as orbital cortex is reciprocally connected with hypothalamus, structural abnormalities in these regions may relate to abnormal decision making, reinforcement learning, or somatic processing in TS.

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Section: Introductionmentioning

confidence: 99%

Brain structure in pediatric Tourette syndrome

et al. 2016

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“…Based on this background, our findings collectively support the construct validity of this TS model. The pathophysiological relevance of D1CT‐7 transgenic mice to TS symptoms is also supported by the recent discovery that TS patients display hyperactivity of the same sensorimotor circuit that is neuropotentiated in these mice (Campbell et al ., ; Bohlhalter et al ., ; Wang et al ., ; Church and Schlaggar, ); furthermore, it is worth noting that recent data indicated that in rodents the optogenetic stimulation of the cortex has been shown to produce features similar to symptoms of OCD – a highly co‐morbid syndrome with TS (Ahmari et al ., ).…”

Section: Discussionmentioning

confidence: 99%

The D1CT‐7 mouse model of Tourette syndrome displays sensorimotor gating deficits in response to spatial confinement

Godar

Mosher

Strathman

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEThe D1CT-7 mouse is one of the best known animal models of Tourette syndrome (TS), featuring spontaneous tic-like behaviours sensitive to standard TS therapies; these characteristics ensure a high face and predictive validity of this model, yet its construct validity remains elusive. To address this issue, we studied the responses of D1CT-7 mice to two critical components of TS pathophysiology: the exacerbation of tic-like behaviours in response to stress and the presence of sensorimotor gating deficits, which are thought to reflect the perceptual alterations causing the tics. EXPERIMENTAL APPROACHD1CT-7 and wild-type (WT) littermates were subjected to a 20 min session of spatial confinement (SC) within an inescapable, 10 cm wide cylindrical enclosure. Changes in plasma corticosterone levels, tic-like behaviours and other spontaneous responses were measured. SC-exposed mice were also tested for the prepulse inhibition (PPI) of the startle response (a sensorimotor gating index) and other TS-related behaviours, including open-field locomotion, novel object exploration and social interaction and compared with non-confined counterparts. KEY RESULTSSC produced a marked increase in corticosterone concentrations in both D1CT-7 and WT mice. In D1CT-7, but not WT mice, SC exacerbated tic-like and digging behaviours, and triggered PPI deficits and aggressive responses. Conversely, SC did not modify locomotor activity or novel object exploration in D1CT-7 mice. Both tic-like behaviours and PPI impairments in SC-exposed D1CT-7 mice were inhibited by standard TS therapies and D1 dopamine receptor antagonism. CONCLUSIONS AND IMPLICATIONSThese findings collectively support the translational and construct validity of D1CT-7 mice with respect to TS. AbbreviationsNC, non-confined; PPI, prepulse inhibition of the acoustic startle reflex; SC, spatial confinement; TS, Tourette syndrome

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“…Furthermore, developmental transcriptome analysis suggested that in adolescence, RICTOR is upregulated in the cerebellar cortex, striatum, and hippocampus. Structural neuroimaging studies have reported a reduction in the volume of the caudate nucleus, one of the striatal structures, in TS patients (Church & Schlaggar, ; Peterson et al, , ), and it has been suggested that smaller caudate volume in childhood correlates with the severity of persistent symptoms observed in adulthood (Bloch, Leckman, Zhu, & Peterson, ). Patients with TS, who are mostly children, demonstrate abnormal volume of the cerebellar cortex (Tobe et al, ) and hippocampus (Peterson, Choi, & Hao, ) and altered dopaminergic function in the hippocampus (Gilbert et al, ), whereas fMRI [Bohlhalter et al, ] and PET (positron emission tomography) (Lerner et al, ; Stern et al, ) have revealed that the cerebellum is involved in tic movements.…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate genes involved in the etiology of sporadic Tourette syndrome by exome sequencing

Eriguchi

Kuwabara

Inai

et al. 2017

American J of Med Genetics Pt B

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Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Although there is a large genetic contribution, the genetic architecture of TS remains unclear. Exome sequencing has successfully revealed the contribution of de novo mutations in sporadic cases with neuropsychiatric disorders such as autism and schizophrenia. Here, using exome sequencing, we investigated de novo mutations in individuals with sporadic TS to identify novel risk loci and elucidate the genetic background of TS. Exome analysis was conducted for sporadic TS cases: nine trio families and one quartet family with concordant twins were investigated. Missense mutations were evaluated using functional prediction algorithms, and their population frequencies were calculated based on three public databases. Gene expression patterns in the brain were analyzed using the BrainSpan Developmental Transcriptome. Thirty de novo mutations, including four synonymous and four missense mutations, were identified. Among the missense mutations, one in the rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR)-coding gene (rs140964083: G > A, found in one proband) was predicted to be hazardous. In the three public databases analyzed, variants in the same SNP locus were absent, and variants in the same gene were either absent or present at an extremely low frequency (3/5,008), indicating the rarity of hazardous RICTOR mutations in the general population. The de novo variant of RICTOR may be implicated in the development of sporadic TS, and RICTOR is a novel candidate factor for TS etiology.

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Pediatric Tourette syndrome: Insights from recent neuroimaging studies

Cited by 32 publications

References 97 publications

Brain structure in pediatric Tourette syndrome

Brain structure in pediatric Tourette syndrome

The D1CT‐7 mouse model of Tourette syndrome displays sensorimotor gating deficits in response to spatial confinement

Identification of candidate genes involved in the etiology of sporadic Tourette syndrome by exome sequencing

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