The Role of Cell Adhesion Molecule Genes Regulating Neuroplasticity in Addiction
Open accessAbstract
A variety of genetic approaches, including twin studies, linkage studies, and candidate gene studies, has established a firm genetic basis for addiction. However, there has been difficulty identifying the precise genes that underlie addiction liability using these approaches. This situation became especially clear in genome-wide association studies (GWAS) of addiction. Moreover, the results of GWAS brought into clarity many of the shortcomings of those early genetic approaches. GWAS studies stripped away those preconceived notions, examining genes that would not previously have been considered in the study of addiction, consequently creating a shift in our understanding. Most importantly, those studies implicated a class of genes that had not previously been considered in the study of addiction genetics: cell adhesion molecules (CAMs). Considering the well-documented evidence supporting a role for various CAMs in synaptic plasticity, axonal growth, and regeneration, it is not surprising that allelic variation in CAM genes might also play a role in addiction liability. This review focuses on the role of various cell adhesion molecules in neuroplasticity that might contribute to addictive processes and emphasizes the importance of ongoing research on CAM genes that have been implicated in addiction by GWAS.
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Gene variants can exert effects indirectly by influencing brain development, personality traits, drug metabolic pathways, neurotransmitters, neural circuitry, or cellular physiology.
“Gene variants can also exert their effects indirectly, by influ encing brain development, including the rate at which frontal connections mature; personality traits that may predispose to drug- seeking, such as sensation seeking; drug metabolic path ways that result in faster or slower degradation of drugs; neu rotransmitters that are directly or indirectly implicated in drug reward and neuroplast”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [98]
The Introduction links variation in cell-adhesion-molecule genes to addiction liability through developmental or later neural plasticity. Section 2.1 also reports associations between NRCAM variants and personality traits, including novelty seeking. The paper does not support the claim’s full list of pathways: it does not describe variants changing drug-degradation rates or the maturation rate of frontal connections. (LLM, conf=0.86)
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References 165 · Cited by 34
Research works printed but not linked: 1
- [47]Long J. C. Knowler W. C. Hanson R. L. Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population American Journal of Medical Genetics 1998 81 3 216 221 10.1002/(SICI)1096-8628(19980508)81:3<216::AID-AJMG2>3.0.CO;2-U 9603607 · DOI
- Authors
- Muskiewicz, D. E., Uhl, G. R., & Hall, F. S.
- Affiliations
- University of Toledo (US)
- National Institute on Drug Abuse (US)
- Corresponding author
- Hall, F. Scott
- Venue
- Neural Plasticity
- Publisher
- Wiley
- Published
- 2018
- Volume
- 2018
- Pages
- 1-17
- ISSN
- 1687-5443 (ISSN-L)
- 2090-5904
- PMC
- PMC5838467
- OpenAlex
- W2793494071
- Cited by
- 34
- References
- 165
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 2 · 2020: 6 · 2019: 1 · 2018: 1
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Neural Plasticity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Drug Abuse
- University of Toledo Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- adhesion molecules, addiction genetics, neuroplasticity, genome-wide association study, synaptic plasticity, axon growth, addiction liability, candidate gene association
- MeSH terms
- Animals, Genotype, Humans, Neuronal Plasticity, Neurons, Phenotype, Cell Adhesion Molecules, Neuronal, Behavior, Addictive, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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