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 language | English (US) |
|---|---|
| Pages (from-to) | 155-177 |
| Number of pages | 23 |
| Journal | International Review of Neurobiology |
| Volume | 112 |
| DOIs | |
| State | Published - 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Genetic susceptibility and neurotransmitters in tourette syndrome
AU - Paschou, Peristera
AU - Fernandez, Thomas V.
AU - Sharp, Frank R
AU - Heiman, Gary A.
AU - Hoekstra, Pieter J.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Dopamine
KW - GABA
KW - Gene expression
KW - Genetics
KW - Glutamate
KW - Histamine
KW - Neurotransmitters
KW - Tourette syndrome
UR - http://www.scopus.com/inward/record.url?scp=84888403130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888403130&partnerID=8YFLogxK
U2 - 10.1016/B978-0-12-411546-0.00006-8
DO - 10.1016/B978-0-12-411546-0.00006-8
M3 - Article
C2 - 24295621
AN - SCOPUS:84888403130
VL - 112
SP - 155
EP - 177
JO - International Review of Neurobiology
JF - International Review of Neurobiology
SN - 0074-7742
ER -