Literature DB >> 27512720

Can Genetic Testing Coupled with Enhanced Dopaminergic Activation Reduce Recidivism Rates in the Workers Compensation Legacy Cases?

Kenneth Blum1, Marlene Oscar-Berman2, Seth H Blum3, Margaret A Madigan4, Roger L Waite4, Thomas McLaughlin3, Debmalya Barh5.   

Abstract

Entities:  

Year:  2014        PMID: 27512720      PMCID: PMC4976629          DOI: 10.4172/2329-6488.1000161

Source DB:  PubMed          Journal:  J Alcohol Drug Depend        ISSN: 2329-6488


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An overwhelming segment of the world’s population possesses certain genetic variations that increase risk for genetic predispositions to substance seeking and even behavioral addictions (e.g. gambling, internet gaming, multiple sex partners etc.) that preclude them from reaching their optimum health potential, contribute to impaired health, and/or can cause involuntary indulgence in detrimental and self-destructive behaviors. This is especially true when this genetic reward deficiency (RDS) [1] problem leads to not only compulsions and excessive cravings but also impaired decision making. This brain hard wiring will ultimately lead to unwanted narcotic addictions; anti-social behavior; crime and unnecessary medical procedures that burden society [2]. It is our notion that the real genesis of all behavior, whether so-called normal or abnormal behavior, derives from an individual’s genetic makeup at birth involving gene variations that make up about 3% of the human genome. While people are not doomed because of carrying these so called variations (called alleles) this risk predisposition, due to multiple gene combinations and polymorphisms (gene variations), is expressed differently based on numerous environmental (epigenetic) elements. So carrying these known gene variants especially in those genes known to control what is called the “Brain Reward Cascade (BRC) influencing how the brain programs feelings of well-being, mediate the actual expression of these important genes [3]. It is well-established that psychiatric disorders are complex multifactorial illnesses involving chronic alterations in the brain reward circuitry. While it is agreed that genetic factors are important in the etiology of disorders such as RDS, relatively high rates of discordance among identical twins suggest the importance of other mechanisms. Certainly, environmental factors such as stress or prior drug exposure play a role in the onset of these illnesses. There is evidence that sustained abnormalities are maintained by epigenetic modifications in specific brain regions. Addictive behavior can be modeled in animals by inducing disease-like states through environmental manipulations (e.g., chronic stress, drug administration) [3]. As David Smith the founder of the Haight-Ashbury Clinic stated “Love Needs Care” and that is what positive caring has in common with powerful epigenetic effects. We firmly embrace this “love and care” concept as part of any treatment goal with the knowledge that through epigenetic effects either methylation and or deacetylation gene expression will lead to positive dopamine release at the reward centers of the brain [4]. Understanding the importance of epigenetics and its effects on chromatin structure will lead to new therapeutic targets to combat for example drug seeking behavior. In fact, we promote the concept that the core of predisposition to these behaviors is a set of genes (called candidate genes), which mediate a feeling of well-being via chemical messenger (i.e. neurotransmitters) interaction at the “reward site” of the brain (N. Accumbens), leading to normal dopamine release and influencing dopamine receptor density (the actual number of dopamine receptors). A low number of Dopamine receptors suggest a hypodopaminergic function as manifested in all addictive disorders. When there are a low number of dopamine receptors, the person will be more prone to seek any substance or behavior that stimulates the dopaminergic system (a sort of “dopamine fix”). In fact, Nora Volkow the current director of the National Institutes of Drug Abuse (NIDA) stated that “all roads lead to dopamine” further described by Blum et al. [5]. To understand generalized craving behavior, due to hypodopaminergic function (a deficiency of reward responsiveness [blunted], individuals self-medicate through biochemical (illicit or non-illicit) attempts to alleviate or compensate for the low dopaminergic brain activity via drug-receptor activation (alcohol, heroin, cocaine, glucose, etc.) [6]. This will substitute for the lack of reward and yield a temporary compensatory sense of well-being. It is this low Dopamine genetic variant that sets these so called “Legacy Case” workers (see below) up for a predisposition for addiction. A very high percentage of these workers are involved in the “injury-treatment-medication-injury” revolving door cycle and may even carry genetic variants (serotonergic and dopaminergic) that result in a higher incident of accidents (e.g. driver accident tendentiousness) for these prone individuals [7]. In order to help explain this so called pseudo self-healing process, we are cognizant of known dysfunctional diagnosis known as “Legacy Cases.” These cases are a major problem within the Workers Compensation insurance carriers system. They are very similar to another dysfunctional diagnose such as Fibromyalgia [8]. Legacy cases are patients with chronic pain that have a monthly narcotic cost of well-over $5,000 per month and have very low functionality in terms of daily living. These claims have been through the gambit of treatments (pharmaceutical, surgical, injections and rehabilitation) with little to no positive outcomes. One reason why these patients do not respond to traditional pain treatments is that they fall into a medical category of “Hypodopaminergic” or Reward Deficiency Syndrome (RDS) [9]. A major problem is that the neuro-circuits of their brains are incapable of having so called normal function of dopamine (called Homeostasis) so they become legal iatrogenic (clinically induced by legally prescribed opioids) addicts [10]. These patients just as the Fibromyalgia patients (which also seem not to respond to traditional therapies) require Dopamine Agonist Modalities (DAM). A number of clinical studies utilizing DAM have shown significant reversal of patients’ craving behavior, reduction of AMA (Against Medical Advice) rates; relapse prevention as well enhancement of quality of life during recovery including happiness (joy) [11]. One of the major underlying problems relating to these Legacy Cases is the inappropriate misdiagnosis and non-productive treatments these patients experience because of utilization of paper-pencil tests rather than sound candidate genetic testing [12]. We strongly believe that especially in low functioning “Legacy Cases” these patients may display high risk due to multiple gene variations across the brain including areas like the Pre-Frontal Cortex Cingulate Gyrus (a site of relapse due to decision –making activity) as well the N. Accumbens (a site of craving behavior). Simply put many of the “Legacy Case” patients’ carry multiple gene variations (neurotransmitters and synthesis producing and metabolic genes) that lead to low Dopamine function (possibly reduced dopamine being released from nerve cells into the synapse (space between two nerve cells) as well as synaptic high breakdown (catabolism) [13]. Correctly, reversing this condition and participating in appropriate treatments will balance their reward brain chemistry by increasing endogenously higher dopamine levels as well as dopamine’s overall reward function. The coupling of genetic testing to determine a person’s genetic risk for addiction and DAM in conjunction with other dopamine promoting effects (i.e. exercise, yoga, electrotherapy, cryotherapy, 12 steps, etc.) will result in pain reduction [14]. Our goal in terms of assisting insurance carriers is to reduce iatrogenic induced opioid addiction by reducing subsequent dependence on these powerful opiates such as even Suboxone thereby promoting “Legacy Case” closure [15]. Closure of these difficult cases will not only benefit the patient’s relief of opioid dependence potentially reducing the “revolving door” phenomena, but will help these insurance carriers to return financial reserves held in abeyance back to the carrier’s general fund. Moreover, utilization of the Genetic Addiction Risk Score (GARSRx™) especially at the portal of entry of patients presenting with either acute or chronic pain will identify patients with high RDS risk and as such will flag these patients’ with genetic knowledge and attenuation of over-prescribed powerful pain reliving opiates at inception of their treatment and physician promotion of subsequent alternatives for pain control (electrotherapy, acupuncture etc.) [16]. Moreover, knowing what the genetic variants are within the BRC will assist the physician in correctly prescribing an effective treatment plan for a better prognosis.

Conclusion

To reiterate utilizing a new paradigm shift in both genetic testing and enhancing functional connectivity of the brain with DAM should improve the health and well-being of the “Legacy Claim” patients because the major underlying root causes of opiate dependency will be reduced. It will additionally curb abuse within the Workers’ Compensation Program and provide a significant monthly cost savings to the carrier and employer. In fact utilizing our approach in a hypodopaminergic genetically tested patient with GARS, having a workers Comp payment for medications over $50,000 per month has been successfully treated with DAM as well as other natural modalities, being opioid free for over two years [17]. Our main mission is to “redeeming joy”™ while inducing higher functionality leading to returning to the workforce. Following additional required research and further confirmation cautious interpretation is encouraged.
  16 in total

1.  Brain reward region responsivity of adolescents with and without parental substance use disorders.

Authors:  Eric Stice; Sonja Yokum
Journal:  Psychol Addict Behav       Date:  2013-10-14

Review 2.  Addiction and brain reward and antireward pathways.

Authors:  Eliot L Gardner
Journal:  Adv Psychosom Med       Date:  2011-04-19

Review 3.  The epigenetic landscape of addiction.

Authors:  Ian Maze; Eric J Nestler
Journal:  Ann N Y Acad Sci       Date:  2011-01       Impact factor: 5.691

Review 4.  Negative dimension in psychiatry. Amotivational syndrome as a paradigm of negative symptoms in substance abuse.

Authors:  Luca Rovai; Angelo Giovanni Icro Maremmani; Matteo Pacini; Pier Paolo Pani; Fabio Rugani; Francesco Lamanna; Elisa Schiavi; Salvatore Mautone; Liliana Dell'Osso; Icro Maremmani
Journal:  Riv Psichiatr       Date:  2013 Jan-Feb       Impact factor: 1.911

5.  [Association of 5-HTTLPR, DRD4 gene polymorphisms with the accident tendentiousness of drivers].

Authors:  Xiao-min Wang; Li Yang; Hai-ying Zhang; Yong Liu; Zheng-hua Tang; Jian Wang; Yan-yan Zheng; Kai-Yong Huang
Journal:  Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi       Date:  2012-07

Review 6.  The addictive brain: all roads lead to dopamine.

Authors:  Kenneth Blum; Amanda L C Chen; John Giordano; Joan Borsten; Thomas J H Chen; Mary Hauser; Thomas Simpatico; John Femino; Eric R Braverman; Debmalya Barh
Journal:  J Psychoactive Drugs       Date:  2012 Apr-Jun

7.  Factors predicting development of opioid use disorders among individuals who receive an initial opioid prescription: mathematical modeling using a database of commercially-insured individuals.

Authors:  Bryan N Cochran; Annesa Flentje; Nicholas C Heck; Jill Van Den Bos; Dan Perlman; Jorge Torres; Robert Valuck; Jean Carter
Journal:  Drug Alcohol Depend       Date:  2014-03-12       Impact factor: 4.492

Review 8.  Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions.

Authors:  Amanda L-C Chen; Thomas J H Chen; Roger L Waite; Jeffrey Reinking; Howard L Tung; Patrick Rhoades; B William Downs; Eric Braverman; Dasha Braverman; Mallory Kerner; Seth H Blum; Nicholas DiNubile; David Smith; Marlene Oscar-Berman; Thomas J Prihoda; John B Floyd; David O'Brien; H H Liu; Kenneth Blum
Journal:  Med Hypotheses       Date:  2008-10-31       Impact factor: 1.538

9.  Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS): Potential Nutrigenomic Induced Dopaminergic Activation.

Authors:  K Blum; M Oscar-Berman; J Giordano; Bw Downs; T Simpatico; D Han; John Femino
Journal:  J Genet Syndr Gene Ther       Date:  2012-10-17

10.  A Multi-Locus Approach to Treating Fibromyalgia by Boosting Dopaminergic Activity in the Meso-Limbic System of the Brain.

Authors:  Kenneth Blum; Marlene Oscar-Berman; Roger L Waite; Eric R Braverman; Florian Kreuk; Mona Li; Kristina Dushaj; Margaret A Madigan; Mary Hauser; Thomas Simpatico; Debmalya Barh
Journal:  J Genet Syndr Gene Ther       Date:  2014-01-27
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  4 in total

Review 1.  Precision Behavioral Management (PBM) and Cognitive Control as a Potential Therapeutic and Prophylactic Modality for Reward Deficiency Syndrome (RDS): Is There Enough Evidence?

Authors:  Margaret A Madigan; Ashim Gupta; Abdalla Bowirrat; David Baron; Rajendra D Badgaiyan; Igor Elman; Catherine A Dennen; Eric R Braverman; Mark S Gold; Kenneth Blum
Journal:  Int J Environ Res Public Health       Date:  2022-05-24       Impact factor: 4.614

2.  Cannabis-Induced Hypodopaminergic Anhedonia and Cognitive Decline in Humans: Embracing Putative Induction of Dopamine Homeostasis.

Authors:  Kenneth Blum; Jag Khalsa; Jean Lud Cadet; David Baron; Abdalla Bowirrat; Brent Boyett; Lisa Lott; Raymond Brewer; Marjorie Gondré-Lewis; Gregory Bunt; Shan Kazmi; Mark S Gold
Journal:  Front Psychiatry       Date:  2021-03-30       Impact factor: 4.157

3.  Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors.

Authors:  Ashim Gupta; Abdalla Bowirrat; Luis Llanos Gomez; David Baron; Igor Elman; John Giordano; Rehan Jalali; Rajendra D Badgaiyan; Edward J Modestino; Mark S Gold; Eric R Braverman; Anish Bajaj; Kenneth Blum
Journal:  Int J Environ Res Public Health       Date:  2022-01-04       Impact factor: 3.390

Review 4.  A Review of DNA Risk Alleles to Determine Epigenetic Repair of mRNA Expression to Prove Therapeutic Effectiveness in Reward Deficiency Syndrome (RDS): Embracing "Precision Behavioral Management".

Authors:  Kenneth Blum; Bruce Steinberg; Marjorie C Gondre-Lewis; David Baron; Edward J Modestino; Rajendra D Badgaiyan; B William Downs; Debasis Bagchi; Raymond Brewer; Thomas McLaughlin; Abdalla Bowirrat; Mark Gold
Journal:  Psychol Res Behav Manag       Date:  2021-12-17
  4 in total

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