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Neural Markers of Genetic Vulnerability to Drug Addiction

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Behavioral Neuroscience of Drug Addiction

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 3))

Abstract

This chapter will summarize genetics findings derived from various strategies and highlight important neural markers (or correlates) in some specific and extensively studied genes. Most studies highlighted here focus on alcohol and nicotine dependence (AD and ND, respectively). AD and ND are among the most prevalent addictive disorders worldwide, are among the best studied, and are also associated globally with the largest socioeconomic impact.

We describe different mechanisms through which genes can have an impact on the addictive behaviors, distinguishing between the genes that inscribe the proteins affecting the metabolism of the addictive substance (e.g., ADH/ALDH for alcohol or CYP2A6 for nicotine) and genes that code for the brain transmitter systems, such as genes involved in cerebral neurotransmission thought to be involved in addiction (e.g., brain reward system, mood regulation, opioid system). Strategies include linkage analyses, association studies, whole genome association studies as well as intermediate/endophenotype studies. Moreover, some important findings derived from animal studies and from neuroimaging studies are highlighted. In conclusion, we provide the reader with an overview of most important studies related to AD and ND and give an outlook how these findings may become useful and beneficial in the future.

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Abbreviations

AD:

Alcohol dependence

ND:

Nicotine dependence

WHO:

World Health Organization

NIAAA:

National Institute on Alcohol Abuse and Alcoholism

DSM-IV:

Diagnostic and Statistical Manual of Mental Disorders edition IV

ICD-10:

International Statistical Classification of Diseases and Related Health Problems

GABA:

Gamma-aminobutyric acid

NMDA:

N-methyl-d-aspartic acid

OPRM1:

Opioid receptor, mu 1

DNA:

Deoxyribonucleic acid

rSA:

Regions for substance abuse

COGA:

Collaborative Study on the Genetics of Alcoholism

ADH:

Alcohol dehydrogenase genes

ALDH:

Aldehyde dehydrogenase genes

DRD2:

Dopamine receptor D2 variants

DRD4:

Dopamine receptor D4 variants

DAT:

Dopamine transporter

DβH:

Dopamine beta-hydroxylase

COMT:

Catechol-O-methyltransferase

CYP2A6:

Cytochrome P450 2A6 enzyme

eCB:

Endocannabinoid

5-HTT:

The serotonin transport protein or 5-hydroxy-tryptamine

ADHD:

Attention-deficit/hyperactivity disorder

MAO-A:

Monoamine-oxidase gene A

WGAS:

Whole genome association study

SNP:

Single nucleotide polymorphism

BOLD:

Blood oxygen level-dependent

HTTLPR:

Serotonin transporter polymorphism in the promoter region

MRI:

Magnetic resonance imaging

fMRI:

Functional MRI

PET:

Positron emission tomography

SPECT:

Single photon emission computed tomography

DTI:

Diffusion tension imaging

CNV:

Copy number variations

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Authors and Affiliations

  1. Department of Psychiatry, Clinic for Psychiatry and Psychotherapy, Charité University Medicine, Campus Charité Mitte, Schumannstrasse 20/21, 10117, Berlin, Germany

    Daniel J. Müller & Andreas Heinz

  2. Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Daniel J. Müller, Olga Likhodi & Andreas Heinz

Authors
  1. Daniel J. Müller
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  2. Olga Likhodi
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  3. Andreas Heinz
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Correspondence to Andreas Heinz .

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Editors and Affiliations

  1. Southwestern Medical Center, University of Texas, Harry Hines Blvd. 5323, Dallas, 75390-9070, U.S.A.

    David W. Self

  2. School of Medicine, Yale University, Campell Ave. 950, West Haven, 06516, U.S.A.

    Julie K. Staley Gottschalk

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Müller, D.J., Likhodi, O., Heinz, A. (2010). Neural Markers of Genetic Vulnerability to Drug Addiction. In: Self, D., Staley Gottschalk, J. (eds) Behavioral Neuroscience of Drug Addiction. Current Topics in Behavioral Neurosciences, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2009_25

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