MAOA expression predicts vulnerability for alcohol use

R. Cervera-Juanes, L. J. Wilhem, B. Park, Richard Lee, J. Locke, C. Helms, S. Gonzales, Gary S Wand, S. R. Jones, K. A. Grant, B. Ferguson

Research output: Contribution to journalArticle

Abstract

The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine-metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue-specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse.

Original languageEnglish (US)
Pages (from-to)472-479
Number of pages8
JournalMolecular Psychiatry
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Monoamine Oxidase
Alcohols
Macaca mulatta
Dopamine
Nucleus Accumbens
Alcohol Drinking
Alcoholism
Cerebrospinal Fluid
3,4-Dihydroxyphenylacetic Acid
Self Administration
Methylation
Serotonin
Genotype
Messenger RNA
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Cervera-Juanes, R., Wilhem, L. J., Park, B., Lee, R., Locke, J., Helms, C., ... Ferguson, B. (2016). MAOA expression predicts vulnerability for alcohol use. Molecular Psychiatry, 21(4), 472-479. https://doi.org/10.1038/mp.2015.93

MAOA expression predicts vulnerability for alcohol use. / Cervera-Juanes, R.; Wilhem, L. J.; Park, B.; Lee, Richard; Locke, J.; Helms, C.; Gonzales, S.; Wand, Gary S; Jones, S. R.; Grant, K. A.; Ferguson, B.

In: Molecular Psychiatry, Vol. 21, No. 4, 01.04.2016, p. 472-479.

Research output: Contribution to journalArticle

Cervera-Juanes, R, Wilhem, LJ, Park, B, Lee, R, Locke, J, Helms, C, Gonzales, S, Wand, GS, Jones, SR, Grant, KA & Ferguson, B 2016, 'MAOA expression predicts vulnerability for alcohol use', Molecular Psychiatry, vol. 21, no. 4, pp. 472-479. https://doi.org/10.1038/mp.2015.93
Cervera-Juanes R, Wilhem LJ, Park B, Lee R, Locke J, Helms C et al. MAOA expression predicts vulnerability for alcohol use. Molecular Psychiatry. 2016 Apr 1;21(4):472-479. https://doi.org/10.1038/mp.2015.93
Cervera-Juanes, R. ; Wilhem, L. J. ; Park, B. ; Lee, Richard ; Locke, J. ; Helms, C. ; Gonzales, S. ; Wand, Gary S ; Jones, S. R. ; Grant, K. A. ; Ferguson, B. / MAOA expression predicts vulnerability for alcohol use. In: Molecular Psychiatry. 2016 ; Vol. 21, No. 4. pp. 472-479.
@article{1d6de147a0264e10be6278c31fec8cbb,
title = "MAOA expression predicts vulnerability for alcohol use",
abstract = "The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine-metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue-specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse.",
author = "R. Cervera-Juanes and Wilhem, {L. J.} and B. Park and Richard Lee and J. Locke and C. Helms and S. Gonzales and Wand, {Gary S} and Jones, {S. R.} and Grant, {K. A.} and B. Ferguson",
year = "2016",
month = "4",
day = "1",
doi = "10.1038/mp.2015.93",
language = "English (US)",
volume = "21",
pages = "472--479",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - MAOA expression predicts vulnerability for alcohol use

AU - Cervera-Juanes, R.

AU - Wilhem, L. J.

AU - Park, B.

AU - Lee, Richard

AU - Locke, J.

AU - Helms, C.

AU - Gonzales, S.

AU - Wand, Gary S

AU - Jones, S. R.

AU - Grant, K. A.

AU - Ferguson, B.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine-metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue-specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse.

AB - The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine-metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue-specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse.

UR - http://www.scopus.com/inward/record.url?scp=84935466220&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84935466220&partnerID=8YFLogxK

U2 - 10.1038/mp.2015.93

DO - 10.1038/mp.2015.93

M3 - Article

VL - 21

SP - 472

EP - 479

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 4

ER -