Genetic Addiction Risk and Psychological Profiling Analyses for “Preaddiction” Severity Index

Abstract

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those at risk for at least alcohol use disorder (AUD), a subset of reward deficiency syndrome (RDS), Blum’s group developed the genetic addiction risk severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions, including pain and even bariatric surgery, as a predictor of severe vulnerability to unwanted addictive behaviors, published since 1990 until now. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. Pearson’s χ2 test or Fisher’s exact test was applied to compare the gender, genotype, and allele distribution if available. The statistical analyses found the OR, 95% CI for OR, and the post risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. Prior to these results, the United States and European patents on a ten gene panel and eleven risk alleles have been issued. In the face of the new construct of the “preaddiction” model, similar to “prediabetes”, the genetic addiction risk analysis might provide one solution missing in the treatment and prevention of the neurological disorder known as RDS.

Invited Expert Opinion- Bio-informatic and Limitation Di-rectives to Help Adopt Ge-netic Addiction Risk Screening and Identify Preaddictive Reward Dysregulation: Re-quired Analytic Evidence to Induce Dopamine Homeo-statsis

“…In seeking an informative scoring of the RDSQ29, we are poised to develop a meaningful trichotomization (mild, moderate, and high) utilizing the precepts of lack of sexual satisfaction, activity, social concerns, and risk-seeking behavior. We believe that when this is accomplished the RDSQ29 would be a valuable tool to help assess preaddiction as discussed in our most recent published article [59] It is noteworthy that Volkow (Director of NIDA) and Koob (director of NIAAA) are encouraging the psychiatric field to include the concept of "preaddiction" as a new inclusion for the DSM. Relevant to this suggestion is the possibility of developing a test to help categorize mild, moderate, or high risk for future addictive-like behaviors.…”

“…In seeking an informative scoring of the RDSQ29, we are poised to develop a meaningful trichotomization (mild, moderate, and high) utilizing the precepts of lack of sexual satisfaction, activity, social concerns, and risk-seeking behavior. We believe that when this is accomplished the RDSQ29 would be a valuable tool to help assess preaddiction as discussed in our most recent published article [ 59 ]…”

Opioid use disorder: current trends and potential treatments

“…Although larger proportion of the population suffer from mild to moderate SUD, public health policies and treatment focus on those with severe, often chronic addictions, to prevent overdoses and deaths, rather than the much larger population grappling with early-stage SUDs. By focusing on those with early-stage addiction, McLellan et al argue that a preaddiction model that looks for early signs of addiction increases public awareness and allows early intervention that can increase disease detection, shorten delays to treatment, and prevent progression ( 42 , 43 ). Directors of the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism have also advocated for the integration of “preaddiction” to the conceptualization of addiction in the DSM.…”

Neurogenetics and Epigenetics of Loneliness

“…90% heritability for height, 162 50% heritability for body mass index 163 and 50% heritability for happiness. 164 Hence symptoms and sequelae of loneliness may be targeted in accordance with individualized formulations, based on genetic risk assessment battery akin to the one designed by us for the assessment of the propensity for addiction 165 in conjunction with clinical assessments, functional neuroimaging, psychotherapy, and psychopharmacology.…”

“…To that end, reward abnormalities can be addressed by the Positive Psychology methods 166 including the Positive Affect Treatment 167 and the Positive Affect Stimulation and Sustainment techniques. 168 Diminished dopaminergic neurotransmission in the mesolimbic pathway underlying reward deficiency, 24,165 presents opportunities for therapeutic interventions including antidepressants and cognitive enhancers like bupropion, 169 solriamfetol, 170 or modafinil. 171 Additional methods for restoring dopaminergic hedonstasis 27,39 include anticonvulsants, atypical antipsychotics, 11,89,172 nootropics, 173 and N-methyl-D-aspartate glutamate receptors' antagonists.…”