CYP2D6 in the brain: genotype effects on resting brain perfusion.
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| Title: | CYP2D6 in the brain: genotype effects on resting brain perfusion. |
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| Authors: | Kirchheiner, J., Seeringer, A., Godoy, A. L., Ohmle, B., Maier, C., Beschoner, P., Sim, E.-J., Viviani, R. |
| Source: | Molecular Psychiatry. Mar2011, Vol. 16 Issue 3, p333-341. 9p. 1 Color Photograph, 3 Charts, 3 Graphs. |
| Subjects: | Cytochrome P-450, Genotype-environment interaction, Hippocampus (Brain), Thalamus, Serotoninergic mechanisms, Phenotypes |
| Abstract: | The cytochrome P450 2D6 (CYP2D6) is a genetically polymorphic enzyme involved in the metabolism of several psychoactive drugs. Beside its expression in the liver, CYP2D6 is highly expressed in several regions of the brain, such as the hippocampus, thalamus, hypothalamus and the cortex, but its function in the brain is not well understood. The CYP2D6 enzyme may also have a physiological role due to its involvement in neurotransmitter biotransformation. In this study, CYP2D6 genotyping was performed in N=188 healthy individuals and compared with brain perfusion levels at rest, which may reflect an ongoing biological process regulating the reactivity of the individual to emotional stimuli and the detection of signals evoking fear. Relative to N=42 matched extensive metabolizers, N=14 poor metabolizers were associated with 15% higher perfusion levels in the thalamus (P=0.03 and 0.003). Effects were also present in the whole (N=188) sample divided into metabolizer groups, or finely graded into seven CYP2D6 activity levels. A weaker effect was observed in the right hippocampus (P=0.05). An exploratory analysis, extended to the whole brain, suggested the involvement of CYP2D6 in regions associated with alertness or serotonergic function. These findings support the hypothesis of a functional role of CYP2D6 in the brain. [ABSTRACT FROM AUTHOR] |
| 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. (Copyright applies to all Abstracts.) | |
| 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: 58537020 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: CYP2D6 in the brain: genotype effects on resting brain perfusion. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Kirchheiner%2C+J%2E%22">Kirchheiner, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Seeringer%2C+A%2E%22">Seeringer, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Godoy%2C+A%2E+L%2E%22">Godoy, A. L.</searchLink><br /><searchLink fieldCode="AR" term="%22Ohmle%2C+B%2E%22">Ohmle, B.</searchLink><br /><searchLink fieldCode="AR" term="%22Maier%2C+C%2E%22">Maier, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Beschoner%2C+P%2E%22">Beschoner, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Sim%2C+E%2E-J%2E%22">Sim, E.-J.</searchLink><br /><searchLink fieldCode="AR" term="%22Viviani%2C+R%2E%22">Viviani, R.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Mar2011, Vol. 16 Issue 3, p333-341. 9p. 1 Color Photograph, 3 Charts, 3 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Cytochrome+P-450%22">Cytochrome P-450</searchLink><br /><searchLink fieldCode="DE" term="%22Genotype-environment+interaction%22">Genotype-environment interaction</searchLink><br /><searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Thalamus%22">Thalamus</searchLink><br /><searchLink fieldCode="DE" term="%22Serotoninergic+mechanisms%22">Serotoninergic mechanisms</searchLink><br /><searchLink fieldCode="DE" term="%22Phenotypes%22">Phenotypes</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The cytochrome P450 2D6 (CYP2D6) is a genetically polymorphic enzyme involved in the metabolism of several psychoactive drugs. Beside its expression in the liver, CYP2D6 is highly expressed in several regions of the brain, such as the hippocampus, thalamus, hypothalamus and the cortex, but its function in the brain is not well understood. The CYP2D6 enzyme may also have a physiological role due to its involvement in neurotransmitter biotransformation. In this study, CYP2D6 genotyping was performed in N=188 healthy individuals and compared with brain perfusion levels at rest, which may reflect an ongoing biological process regulating the reactivity of the individual to emotional stimuli and the detection of signals evoking fear. Relative to N=42 matched extensive metabolizers, N=14 poor metabolizers were associated with 15% higher perfusion levels in the thalamus (P=0.03 and 0.003). Effects were also present in the whole (N=188) sample divided into metabolizer groups, or finely graded into seven CYP2D6 activity levels. A weaker effect was observed in the right hippocampus (P=0.05). An exploratory analysis, extended to the whole brain, suggested the involvement of CYP2D6 in regions associated with alertness or serotonergic function. These findings support the hypothesis of a functional role of CYP2D6 in the brain. [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.2010.42 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 333 Subjects: – SubjectFull: Cytochrome P-450 Type: general – SubjectFull: Genotype-environment interaction Type: general – SubjectFull: Hippocampus (Brain) Type: general – SubjectFull: Thalamus Type: general – SubjectFull: Serotoninergic mechanisms Type: general – SubjectFull: Phenotypes Type: general Titles: – TitleFull: CYP2D6 in the brain: genotype effects on resting brain perfusion. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Kirchheiner, J. – PersonEntity: Name: NameFull: Seeringer, A. – PersonEntity: Name: NameFull: Godoy, A. L. – PersonEntity: Name: NameFull: Ohmle, B. – PersonEntity: Name: NameFull: Maier, C. – PersonEntity: Name: NameFull: Beschoner, P. – PersonEntity: Name: NameFull: Sim, E.-J. – PersonEntity: Name: NameFull: Viviani, R. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: Mar2011 Type: published Y: 2011 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 16 – Type: issue Value: 3 Titles: – TitleFull: Molecular Psychiatry Type: main |
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