Association of the Neuronal Cell Adhesion Molecule (NrCAM) Gene Variants with Personality Traits and Addictive Symptoms in Methamphetamine Use Disorder

Abstract

Objective1) To investigate the relationship between NrCAM polymorphisms and methamphetamine abuse in an ethnically homogenous Korean population. 2) To further support our findings by investigating the association among NrCAM gene variants, certain personality traits, and addictive symptoms of methamphetamine abusers.MethodsThirty-seven male methamphetamine abusers (age=43.3±7.8) and30 non-users (16 men, 14 women; age=59.8±10.4) were recruited. Ten single nucleotide polymorphisms (SNPs) in the NrCAM gene were assayed to compare genotype distributions between the 2 groups. Personality characteristics were measured using the Temperament and Character Inventory (TCI) and the NEO Personality Inventory, Revised (NEO PI-R). Addictive symptoms were assessed using the Diagnostic Interview for Genetic Studies (DIGS) and reviews of the subject's medical records.ResultsAmong the 10 SNPs in the NrCAM gene, the frequency of the TA genotype at rs1990162 was significantly lower in methamphetamine abusers compared to non-users (p=0.042). In the 3 NrCAM gene SNPs (rs381318, rs2072546, and rs6954366), the distribution of genotypes and alleles were significantly associated with some traits in the TCI and NEO PI-R. Genotypes and alleles at 5 gene SNPs (rs2142325, rs381318, rs1269621, rs1269634, and rs1990162) were associated with certain addictive symptom dimensions in the patients.ConclusionThese findings support the idea that NrCAM is associated with genetic susceptibility of methamphetamine abuse and is also associated with certain personality characteristics that may increase disturbed addictive behavior.

Severity of Demyelinating and Axonal Neuropathy Mouse Models Is Modified by Genes Affecting Structure and Function of Peripheral Nodes

“…The SCN8A gene in humans is associated with cognitive impairment with and without cerebellar ataxia, and early infantile epileptic encephalopathy, and in mice it causes the motor endplate degeneration ( med ) phenotype (Burgess et al, 1995; Trudeau et al, 2006; Veeramah et al, 2012; O’Brien and Meisler, 2013). Nrcam mutations are associated with neurodevelopmental disorders and addictive behaviors in humans (Bonora et al, 2005; Sakurai et al, 2006; Ishiguro et al, 2006; Kim et al, 2009; Marui et al, 2009; Yoo et al, 2012). However, our point is not to make a direct case for NRCAM or SCN8A as human disease modifiers for CMT (indeed, their clinical associations are more severe than the “subclinical” mouse mutations we are describing) but instead to use them as a demonstration of the principle that variants that impact nodes will lead to more severe CMT phenotypes.…”

Pathway analysis of genome‐wide association datasets of personality traits

“…Interestingly, over the last few years, a number of studies have reported that schizophrenia and bipolar disorder, as well as other psychiatric disorders, were associated with CAM, which is responsible for synapse formation and normal cell transmission (Corvin ; O'dushlaine et al ). Besides, neuronal CAM has been associated with drug abuse and personality characteristics such as novelty seeking and reward dependence (Yoo et al ). Additionally, the contribution of potassium channels, which were enriched gene sets for Extraversion in this study, has been reported in psychiatric disorders (Judy & Zandi ; Zhang et al ).…”

Genetic association of impulsivity in young adults: a multivariate study

“…Neuronal CAM has been associated with drug abuse and personality characteristics such as novelty seeking and reward dependence. 48 Focal adhesion pathways are responsible for cell motility, proliferation, differentiation, survival and regulation of gene expression, 49 and have a major role in central nervous system development. The mitogen-activated protein kinase signaling pathway significantly associated with GC1 and GC2 is involved in cellular proliferation, differentiation and migration.…”