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MAOA expression predicts vulnerability for alcohol use

Molecular Psychiatry volume 21, pages 472–479 (2016)Cite this article

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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.

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Acknowledgements

This study was supported by NIH grants U01AA020928 (BF), U01AA013510 (KAG), U01AA020890 (GW), U01AA014091 (SRJ), R24AA019431 (KAG), OD011092 (from ONPRC) and the Margaret Ann Price Investigator Fund (RL), James Wah Mood Disorders Scholar Fund via Charles T. Bauer Foundation (RL) and The Kenneth Lattman Foundation (GW). We are grateful to the ONPRC’s Department of Comparative Medicine and Primate Genetics Core Services for their assistance in this project. We thank Dr Julie Hollister-Smith for her technical support and helpful comments. We also appreciate the very helpful critiques provided by the anonymous reviewers.

Author contributions

BF, SRJ, KAG and RC-J were responsible for the study concept and design. KAG provided the animal samples. CH performed the tissue dissections. SG provided the alcohol- and water-intake data. RC-J performed DNA and RNA isolation, real-time PCR analysis and bisulfite sequencing. RL performed the initial bisulfite pyrosequencing analysis. LJW performed the informatics analysis of the bisulfite data. BP contributed statistical analysis. RC-J, JL, LJW, RL and BF assisted with data analysis and interpretation of findings. RC-J and BF drafted the manuscript. SRJ, RL, GW, KAG and BP provided critical revision of the manuscript for important intellectual content. All authors critically reviewed content and approved the final version for publication.

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Authors and Affiliations

  1. Department of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA

    R Cervera-Juanes, L J Wilhem, C Helms, S Gonzales, K A Grant & B Ferguson

  2. Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, USA

    B Park

  3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA

    R Lee & G Wand

  4. Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, NC, USA

    J Locke & S R Jones

  5. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    G Wand

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  1. R Cervera-Juanes
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Correspondence to B Ferguson.

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Cervera-Juanes, R., Wilhem, L., Park, B. et al. MAOA expression predicts vulnerability for alcohol use. Mol Psychiatry 21, 472–479 (2016). https://doi.org/10.1038/mp.2015.93

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