The Genetic Basis of Addictive Disorders

Ducci, Francesca; Goldman, David

doi:10.1016/j.psc.2012.03.010

Cited by 303Neurotransmitter Receptor Influence on BehaviorGenetic Associations and EpidemiologySubstance Abuse Treatment and Outcomes

The Genetic Basis of Addictive Disorders

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Ducci, Francesca, Goldman, David·2012·Psychiatric Clinics of North America

DOI 10.1016/j.psc.2012.03.010PMC PMC3506170

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Abstract

Addictions are common, chronic, and relapsing diseases that develop through a multistep process. The impact of addictions on morbidity and mortality is high worldwide. Twin studies have shown that the heritability of addictions ranges from 0.39 (hallucinogens) to 0.72 (cocaine). Twin studies indicate that genes influence each stage from initiation to addiction, although the genetic determinants may differ. Addictions are by definition the result of gene × environment interaction. These disorders, which are in part volitional, in part inborn, and in part determined by environmental experience, pose the full range of medical, genetic, policy, and moral challenges. Gene discovery is being facilitated by a variety of powerful approaches, but is in its infancy. It is not surprising that the genes discovered so far act in a variety of ways: via altered metabolism of drug (the alcohol and nicotine metabolic gene variants), via altered function of a drug receptor (the nicotinic receptor, which may alter affinity for nicotine but as discussed may also alter circuitry of reward), and via general mechanisms of addiction (genes such as monoamine oxidase A and the serotonin transporter that modulate stress response, emotion, and behavioral control). Addiction medicine today benefits from genetic studies that buttress the case for a neurobiologic origin of addictive behavior, and some general information on familially transmitted propensity that can be used to guide prevention. A few well-validated, specific predictors such as OPRM1, ADH1B, ALDH2, CHRNA5, and CYP26 have been identified and can provide some specific guidance, for example, to understand alcohol-related flushing and upper GI cancer risk (ADH1B and AKLDH2), variation in nicotine metabolism (CYP26), and, potentially, naltrexone treatment response (OPRM1). However, the genetic predictors available are few in number and account for only a small portion of the genetic variance in liability, and have not been integrated into clinical nosology or care.

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The progression of StUD is influenced by multiple factors, including stimulant potency and pharmacokinetics, frequency of use, route of administration, and age at first use.
“Many factors influence the progression of StUD, including the potency and pharmacokinetics of the stimulants used, frequency of use, route of administration, and age of first use, among others.19,20”
From The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder (2024) · cites this paper as [20]
The paper’s opening section says progression toward problematic use is influenced by age at first use, the agent’s psychoactive properties and pharmacokinetics, and mode of administration. It also links repetitive exposure to the development of addiction. These passages discuss addiction and substance use disorders generally, however, rather than establishing the full list specifically for stimulant use disorder; they do not explicitly identify stimulant potency or frequency of use as factors. (LLM, conf=0.86)
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HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power—an intermediate phenotype for alcoholism and co-morbid behaviors
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Deconstruction of Vulnerability to Complex Diseases: Enhanced Effect Sizes and Power of Intermediate Phenotypes
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Monoamine Oxidase A Genotype Predicts Human Serotonin 1A Receptor AvailabilityIn Vivo
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Increased anxiety and other similarities in temperament of alcoholics with and without antisocial personality disorder across three diverse populations
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Thermal stability and the biochemical genetics of erythrocyte catechol‐O‐methyltransferase and plasma dopamine‐β‐hydroxylase
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Glucocorticoid receptor (NR3C1) gene polymorphisms and onset of alcohol abuse in adolescents
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A COMT gene haplotype associated with methamphetamine abuse
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Recognition of scared faces and the serotonin transporter gene in young children: the Generation R Study
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Correction for Schumann et al., Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
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(1997) · doi:10.1002/(sici)1096-8628(19970725)74:4

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Authors: Ducci, F., & Goldman, D.
Affiliations: King's College London (GB)
National Institutes of Health (US)
Corresponding author: Goldman, David
ORCID: Goldman, David
Venue: Psychiatric Clinics of North America
Publisher: Elsevier BV
Published: 2012-06
Volume: 35
Issue: 2
Pages: 495-519
ISSN: 0193-953X (ISSN-L)
DOI: 10.1016/j.psc.2012.03.010
PMC: PMC3506170
OpenAlex: W1972225113
Cited by: 303
References: 134
Citations by year: 2026: 11 · 2025: 26 · 2024: 26 · 2023: 16 · 2022: 31 · 2021: 35 · 2020: 20 · 2019: 55 · 2018: 19 · 2017: 17 · 2016: 8 · 2015: 15 · 2014: 11 · 2013: 12 · 2012: 1
FWCI: 5.10
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Psychiatric Clinics of North America (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism (Z01AA000301, K24AA000301)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords: addiction, heritability, gene-environment interaction, twin studies, gene discovery, nicotine metabolism, nicotinic acetylcholine receptors, monoamine oxidase A, serotonin transporter, reward systems, ADH1B, ALDH2, OPRM1, genetic risk prediction, addiction prevention, family transmission
MeSH terms: Aldehyde Dehydrogenase, Mitochondrial, Adolescent, Adult, Alcohol Dehydrogenase, Ethanol, Aldehyde Dehydrogenase, Alleles, Catechol O-Methyltransferase, Child, Epistasis, Genetic, Female, Humans, Male, Models, Genetic, Monoamine Oxidase, Polymorphism, Genetic, Risk Factors, Smoking, Social Environment, Twins, Comorbidity, Behavior, Addictive, Twin Studies as Topic, Substance-Related Disorders, Genetic Predisposition to Disease, Receptor, Serotonin, 5-HT1B, Serotonin Plasma Membrane Transport Proteins, Genetic Association Studies, Endophenotypes, Gene-Environment Interaction

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The Genetic Basis of Addictive Disorders

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