Tryptophan hydroxylase2 gene polymorphisms predict brain serotonin synthesis in the orbitofrontal cortex in humans.
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| Title: | Tryptophan hydroxylase |
|---|---|
| Authors: | Booij, L, Turecki, G, Leyton, M, Gravel, P, Lopez De Lara, C, Diksic, M, Benkelfat, C |
| Source: | Molecular Psychiatry. Aug2012, Vol. 17 Issue 8, p809-817. 9p. 2 Color Photographs, 3 Charts. |
| Subjects: | Tryptophan hydroxylase, Genetic polymorphisms, Serotonin, Neural development, Mental depression, Suicide |
| Abstract: | Brain regional serotonin synthesis can be estimated in vivo using positron emission tomography (PET) and α-[(11)C]methyl-L-tryptophan (11C-AMT) trapping (K*) as a proxy. Recently, we reported evidence of lower normalized 11C-AMT trapping in the orbitofrontal cortex (OBFC) of subjects meeting the criteria for an impulsive and/or aggressive behavioral phenotype. In this study, we examined whether part of the variance in OBFC serotonin synthesis is related to polymorphisms of the gene that encodes for the indoleamine's rate-limiting enzyme in the brain, tryptophan hydroxylase-2 (TPH2). In all, 46 healthy controls had PET 11C-AMT scans and were genotyped for 11 single-nucleotide polymorphisms (SNPs) distributed across the TPH2 gene and its 5′ upstream region. Several TPH2 SNPs were associated with lower normalized blood-to-brain clearance of 11C-AMT in the OBFC. Dose-effect relationships were found for two variants (rs6582071 and rs4641527, respectively, located in the 5′ upstream region and intron 1) that have previously been associated with suicide. Associations in the OBFC remained statistically significant in a mixed larger sample of patients and controls. These results suggest that in humans, genetic factors might partly account for variations in serotonin synthesis in the OBFC. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 78029247 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Tryptophan hydroxylase<subscript>2</subscript> gene polymorphisms predict brain serotonin synthesis in the orbitofrontal cortex in humans. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Booij%2C+L%22">Booij, L</searchLink><br /><searchLink fieldCode="AR" term="%22Turecki%2C+G%22">Turecki, G</searchLink><br /><searchLink fieldCode="AR" term="%22Leyton%2C+M%22">Leyton, M</searchLink><br /><searchLink fieldCode="AR" term="%22Gravel%2C+P%22">Gravel, P</searchLink><br /><searchLink fieldCode="AR" term="%22Lopez+De+Lara%2C+C%22">Lopez De Lara, C</searchLink><br /><searchLink fieldCode="AR" term="%22Diksic%2C+M%22">Diksic, M</searchLink><br /><searchLink fieldCode="AR" term="%22Benkelfat%2C+C%22">Benkelfat, C</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Aug2012, Vol. 17 Issue 8, p809-817. 9p. 2 Color Photographs, 3 Charts. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Tryptophan+hydroxylase%22">Tryptophan hydroxylase</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Serotonin%22">Serotonin</searchLink><br /><searchLink fieldCode="DE" term="%22Neural+development%22">Neural development</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Suicide%22">Suicide</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Brain regional serotonin synthesis can be estimated in vivo using positron emission tomography (PET) and α-[(11)C]methyl-L-tryptophan (11C-AMT) trapping (K*) as a proxy. Recently, we reported evidence of lower normalized 11C-AMT trapping in the orbitofrontal cortex (OBFC) of subjects meeting the criteria for an impulsive and/or aggressive behavioral phenotype. In this study, we examined whether part of the variance in OBFC serotonin synthesis is related to polymorphisms of the gene that encodes for the indoleamine's rate-limiting enzyme in the brain, tryptophan hydroxylase-2 (TPH2). In all, 46 healthy controls had PET 11C-AMT scans and were genotyped for 11 single-nucleotide polymorphisms (SNPs) distributed across the TPH2 gene and its 5′ upstream region. Several TPH2 SNPs were associated with lower normalized blood-to-brain clearance of 11C-AMT in the OBFC. Dose-effect relationships were found for two variants (rs6582071 and rs4641527, respectively, located in the 5′ upstream region and intron 1) that have previously been associated with suicide. Associations in the OBFC remained statistically significant in a mixed larger sample of patients and controls. These results suggest that in humans, genetic factors might partly account for variations in serotonin synthesis in the OBFC. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/mp.2011.79 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 809 Subjects: – SubjectFull: Tryptophan hydroxylase Type: general – SubjectFull: Genetic polymorphisms Type: general – SubjectFull: Serotonin Type: general – SubjectFull: Neural development Type: general – SubjectFull: Mental depression Type: general – SubjectFull: Suicide Type: general Titles: – TitleFull: Tryptophan hydroxylase2 gene polymorphisms predict brain serotonin synthesis in the orbitofrontal cortex in humans. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Booij, L – PersonEntity: Name: NameFull: Turecki, G – PersonEntity: Name: NameFull: Leyton, M – PersonEntity: Name: NameFull: Gravel, P – PersonEntity: Name: NameFull: Lopez De Lara, C – PersonEntity: Name: NameFull: Diksic, M – PersonEntity: Name: NameFull: Benkelfat, C IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 08 Text: Aug2012 Type: published Y: 2012 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 17 – Type: issue Value: 8 Titles: – TitleFull: Molecular Psychiatry Type: main |
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