Genetic susceptibility and neurotransmitters in tourette syndrome

Peristera Paschou, Thomas V. Fernandez, Frank R Sharp, Gary A. Heiman, Pieter J. Hoekstra

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Family studies have consistently shown that Tourette syndrome (TS) is a familial disorder and twin studies have clearly indicated a genetic contribution in the etiology of TS. Whereas early segregation studies of TS suggested a single-gene autosomal dominant disorder, later studies have pointed to more complex models including additive and multifactorial inheritance and likely interaction with genetic factors. While the exact cellular and molecular base of TS is as yet elusive, neuroanatomical and neurophysiological studies have pointed to the involvement of cortico-striato-thalamocortical circuits and abnormalities in dopamine, glutamate, gamma-aminobutyric acid, and serotonin neurotransmitter systems, with the most consistent evidence being available for involvement of dopamine-related abnormalities, that is, a reduction in tonic extracellular dopamine levels along with hyperresponsive spike-dependent dopamine release, following stimulation. Genetic and gene expression findings are very much supportive of involvement of these neurotransmitter systems. Moreover, intriguingly, genetic work on a two-generation pedigree has opened new research pointing to a role for histamine, a so far rather neglected neurotransmitter, with the potential of the development of new treatment options. Future studies should be aimed at directly linking neurotransmitter-related genetic and gene expression findings to imaging studies (imaging genetics), which enables a better understanding of the pathways and mechanisms through which the dynamic interplay of genes, brain, and environment shapes the TS phenotype.

Original languageEnglish (US)
Pages (from-to)155-177
Number of pages23
JournalInternational Review of Neurobiology
Volume112
DOIs
StatePublished - 2013

Fingerprint

Tourette Syndrome
Genetic Predisposition to Disease
Neurotransmitter Agents
Dopamine
Multifactorial Inheritance
Gene Expression
Dominant Genes
Twin Studies
Pedigree
gamma-Aminobutyric Acid
Histamine
Glutamic Acid
Serotonin
Phenotype
Brain
Research
Genes

Keywords

  • Dopamine
  • GABA
  • Gene expression
  • Genetics
  • Glutamate
  • Histamine
  • Neurotransmitters
  • Tourette syndrome

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Genetic susceptibility and neurotransmitters in tourette syndrome. / Paschou, Peristera; Fernandez, Thomas V.; Sharp, Frank R; Heiman, Gary A.; Hoekstra, Pieter J.

In: International Review of Neurobiology, Vol. 112, 2013, p. 155-177.

Research output: Contribution to journalArticle

Paschou, Peristera ; Fernandez, Thomas V. ; Sharp, Frank R ; Heiman, Gary A. ; Hoekstra, Pieter J. / Genetic susceptibility and neurotransmitters in tourette syndrome. In: International Review of Neurobiology. 2013 ; Vol. 112. pp. 155-177.
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