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Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).

ABSTRACT: Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followed seminal research in 1990, whereby, Blum's group identified the first genetic association with severe alcoholism published in JAMA. While it is true that no one to date has provided adequate RDS free controls there have been many studies using case -controls whereby SUD has been eliminated. We argue that this deficiency needs to be addressed in the field and if adopted appropriately many spurious results would be eliminated reducing confusion regarding the role of genetics in addiction. However, an estimation, based on these previous literature results provided herein, while not representative of all association studies known to date, this sampling of case- control studies displays significant associations between alcohol and drug risk. In fact, we present a total of 110,241 cases and 122,525 controls derived from the current literature. We strongly suggest that while we may take argument concerning many of these so-called controls (e.g. blood donors) it is quite remarkable that there are a plethora of case -control studies indicating selective association of these risk alleles ( measured in GARS) for the most part indicating a hypodopaminergia. The paper presents the detailed methodology of the GARS. Data collection procedures, instrumentation, and the analytical approach used to obtain GARS and subsequent research objectives are described. Can we combat SUD through early genetic risk screening in the addiction field enabling early intervention by the induction of dopamine homeostasis? It is envisaged that GARS type of screening will provide a novel opportunity to help identify causal pathways and associated mechanisms of genetic factors, psychological characteristics, and addictions awaiting additional scientific evidence including a future meta- analysis of all available data -a work in progress.

SUBMITTER: Blum K

PROVIDER: S-EPMC7891477 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).

Blum K K Bowirrat A A Baron D D Lott L L Ponce J V JV Brewer R R Siwicki D D Boyett B B Gondre-Lewis M C MC Smith D E DE Panayotis K Thanos T Badgaiyan S S Hauser M M Fried L L A Roy R Downs B W BW Badgaiyan R D RD

Journal of systems and integrative neuroscience 20191219 2

Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followe ...[more]

PMID: 33614164

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Project description:Background and aimsThe focus of this paper is on the improvement of substance use disorder (SUD) screening and measurement. Using a multi-dimensional item response theory model, the bifactor model, we provide a psychometric harmonization between SUD, depression, anxiety, trauma, social isolation, functional impairment and risk-taking behavior symptom domains, providing a more balanced view of SUD. The aims are to (1) develop the item-bank, (2) calibrate the item-bank using a bifactor model that includes a primary dimension and symptom-specific subdomains, (3) administer using computerized adaptive testing (CAT) and (4) validate the CAT-SUD in Spanish and English in the United States and Spain.DesignItem bank construction, item calibration phase, CAT-SUD validation phase.SettingPrimary care, community clinics, emergency departments and patient-to-patient referrals in Spain (Barcelona and Madrid) and the United States (Boston and Los Angeles).Participants/casesCalibration phase: the CAT-SUD was developed via simulation from complete item responses in 513 participants. Validation phase: 297 participants received the Composite International Diagnostic Interview (CIDI) and the CAT-SUD.MeasurementsA total of 252 items from five subdomains: (1) SUD, (2) psychological disorders, (3) risky behavior, (4) functional impairment and (5) social support. CAT-SUD scale scores and CIDI SUD diagnosis.FindingsCalibration: the bifactor model provided excellent fit to the multi-dimensional item bank; 168 items had high loadings (> 0.4 with the majority > 0.6) on the primary SUD dimension. Using an average of 11 items (four to 26), which represents a 94% reduction in respondent burden (average administration time of approximately 2 minutes), we found a correlation of 0.91 with the 168-item scale (precision of 5 points on a 100-point scale).Validationstrong agreement was found between the primary CAT-SUD dimension estimate and the results of a structured clinical interview. There was a 20-fold increase in the likelihood of a CIDI SUD diagnosis across the range of the CAT-SUD (AUC = 0.85).ConclusionsWe have developed a new approach for the screening and measurement of SUD and related severity based on multi-dimensional item response theory. The bifactor model harmonized information from mental health, trauma, social support and traditional SUD items to provide a more complete characterization of SUD. The CAT-SUD is highly predictive of a current SUD diagnosis based on a structured clinical interview, and may be predictive of the development of SUD in the future.

Dataset Information

Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).

Publications

Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).

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