The Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors as well as altered pain tolerance. While there are many studies claiming a genetic association with addiction and other behavioral infractions, defined as Reward Deficiency Syndrome (RDS), not all are scientifically accurate and in some case just wrong. Albeit our bias, we discuss herein the facts and fictions behind molecular genetic testing in RDS (including pain and addiction) and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™), the first test to accurately predict one's genetic risk for RDS.
Abstract There are a number of epidemiological studies concerning the gender differences in the genetic etiology of alcohol dependence (AD), with ADH2 and ALDH2 being strong candidates. The purpose of this study was to investigate gender differences in frequencies of ADH2 and ALDH2 genotypes in AD patients and in a normal control (NC) group of Koreans. Study subjects consisted of 228 AD patients (180 males, 48 females) and 138 NC (79 males, 59 females). For both male and female subjects, the frequency of the ADH2*1/1 genotype was significantly higher in AD patients compared to the NC group. However, the effect size of the ADH2*1/1 genotype on AD was much larger in females than in males. Furthermore, the ALDH2*1/1 genotype was positively associated with AD in male subjects but negatively associated with AD in female patients. Interestingly, AD in males was primarily determined by ALDH2 enzyme activity (92%), whereas female AD was primarily determined by ADH2 enzyme activity (60.4%). These results suggest that risk for the development of AD in males is mainly associated with the ALDH2*1/1 genotype, while in female patients, the ADH2*1/1 genotype was more highly associated with risk of AD. Overall, it is evident that gender differences associated with genetic risks for AD are present.
Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions Individual mice differ in the dose of ethanol they will ingest voluntarily when it is offered during limited access periods in the circadian dark, a phenotype called drinking in the dark (DID). Substantial genetic variation in DID has been reported across a few standard inbred mouse strains, and a line of High Drinking in the Dark (HDID) mice has been established through selective breeding on the blood ethanol concentration (BEC) they attain at the end of a drinking session. Here, we report ethanol DID data for 23 inbred mouse strains, including 11 not previously reported, corroborating the genetic contributions to this trait. We also report data on a different ethanol drinking trait, the increased intake seen after multiple cycles of chronic intermittent exposure to ethanol vapor (CIE). Drinking escalated significantly during ethanol withdrawal. However, HDID mice and their HS controls showed equivalent escalation during withdrawal, demonstrating that withdrawal-associated drinking escalation is not a clear genetic correlate of selection on DID. Across inbred strains, DID is substantially genetically correlated with previously-published twobottle ethanol preference drinking data assessed under conditions of continuous ethanol access. Although inbred strain data for withdrawalassociated drinking are not available, the current pattern of results suggests that withdrawal-associated drinking is genetically distinct from DID, while genetic contributions to DID and two-bottle preference drinking are substantially similar.
