Prefrontal white matter impairment in substance users depends upon the catechol-o-methyl transferase (COMT) val158met polymorphism
Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn...
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| Published in | NeuroImage (Orlando, Fla.) Vol. 69; pp. 62 - 69 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Amsterdam
Elsevier Inc
01.04.2013
Elsevier Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1053-8119 1095-9572 1095-9572 |
| DOI | 10.1016/j.neuroimage.2012.11.056 |
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| Abstract | Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant Genotype×Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction.
► Significant COMTval158met×Drug Use interaction in prefrontal white matter was found. ► Reduced prefrontal FA was found only in Met allele homozygotes who are also drug users. ► Elevated prefrontal dopamine and drug may interact to alter white matter structure. ► Relevance to known prefrontal cortical deficits in addiction is discussed. |
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| AbstractList | Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant Genotype Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction. Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant Genotype × Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction. Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant Genotype×Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction. Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant Genotype × Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction.Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant Genotype × Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction. Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant GenotypexDrug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction. Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant Genotype×Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction. ► Significant COMTval158met×Drug Use interaction in prefrontal white matter was found. ► Reduced prefrontal FA was found only in Met allele homozygotes who are also drug users. ► Elevated prefrontal dopamine and drug may interact to alter white matter structure. ► Relevance to known prefrontal cortical deficits in addiction is discussed. |
| Author | Shen, Pei-Hong Hong, L. Elliot Zhang, Xiaochu Li, Nan Ross, Thomas J. Geng, Xiujuan Goldman, David Stein, Elliot A. Yang, Yihong Stein, Dan J. Lee, Mary R. Hodgkinson, Colin Salmeron, Betty Jo |
| AuthorAffiliation | 1. Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, Maryland 21224 2. Dept of Psychiatry and Mental Health., Univ. of Cape Town, Cape Town, South Africa 3. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21228 4. Laboratory of Neurogenetics, DICBR, NIAAA, NIH, Rockville, MD 5. Key Laboratory of Brain Function and Diseases, Chinese Academy of Sciences, and School of Life Sciences, University of Science and Technology of China, Hefei 230027 |
| AuthorAffiliation_xml | – name: 2. Dept of Psychiatry and Mental Health., Univ. of Cape Town, Cape Town, South Africa – name: 4. Laboratory of Neurogenetics, DICBR, NIAAA, NIH, Rockville, MD – name: 5. Key Laboratory of Brain Function and Diseases, Chinese Academy of Sciences, and School of Life Sciences, University of Science and Technology of China, Hefei 230027 – name: 1. Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, Maryland 21224 – name: 3. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21228 |
| Author_xml | – sequence: 1 givenname: Xiaochu surname: Zhang fullname: Zhang, Xiaochu organization: Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA – sequence: 2 givenname: Mary R. surname: Lee fullname: Lee, Mary R. email: leemary@mail.nih.gov organization: Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA – sequence: 3 givenname: Betty Jo surname: Salmeron fullname: Salmeron, Betty Jo organization: Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA – sequence: 4 givenname: Dan J. surname: Stein fullname: Stein, Dan J. organization: Dept of Psychiatry and Mental Health., Univ. of Cape Town, Cape Town, South Africa – sequence: 5 givenname: L. Elliot surname: Hong fullname: Hong, L. Elliot organization: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA – sequence: 6 givenname: Xiujuan surname: Geng fullname: Geng, Xiujuan organization: Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA – sequence: 7 givenname: Thomas J. surname: Ross fullname: Ross, Thomas J. organization: Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA – sequence: 8 givenname: Nan surname: Li fullname: Li, Nan organization: Key Laboratory of Brain Function and Diseases, Chinese Academy of Sciences, and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China – sequence: 9 givenname: Colin surname: Hodgkinson fullname: Hodgkinson, Colin organization: Laboratory of Neurogenetics, DICBR, NIAAA, NIH, Rockville, MD, USA – sequence: 10 givenname: Pei-Hong surname: Shen fullname: Shen, Pei-Hong organization: Laboratory of Neurogenetics, DICBR, NIAAA, NIH, Rockville, MD, USA – sequence: 11 givenname: Yihong surname: Yang fullname: Yang, Yihong organization: Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA – sequence: 12 givenname: David surname: Goldman fullname: Goldman, David organization: Laboratory of Neurogenetics, DICBR, NIAAA, NIH, Rockville, MD, USA – sequence: 13 givenname: Elliot A. surname: Stein fullname: Stein, Elliot A. organization: Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA |
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| Keywords | DTI Genetics Addiction COMT Imaging Nicotine Enzyme Transferases White matter Polymorphism |
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| SubjectTerms | Addiction Addictive behaviors Adult Anisotropy Behavior Biological and medical sciences Catechol O-Methyltransferase - genetics Cocaine COMT Diffusion Magnetic Resonance Imaging Dopamine Drug use DTI Female Fundamental and applied biological sciences. Psychology Genetics Genotype Heroin Humans Image Interpretation, Computer-Assisted Imaging Male Nicotine Polymorphism, Single Nucleotide Prefrontal Cortex - pathology Substance-Related Disorders - genetics Substance-Related Disorders - pathology Vertebrates: nervous system and sense organs |
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| Title | Prefrontal white matter impairment in substance users depends upon the catechol-o-methyl transferase (COMT) val158met polymorphism |
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