Literature DB >> 34707969

Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development.

Kenneth Blum1,2,3,4,5,6, Abdalla Bowirrat7, Marjorie C Gondre Lewis8, Thomas A Simpatico4, Mauro Ceccanti9, Bruce Steinberg10, Edward J Modestino10, Panayotis K Thanos11, David Baron1, Thomas McLaughlin12, Raymond Brewer5, Rajendra D Badgaiyan13, Jessica Valdez Ponce5, Lisa Lott5, Mark S Gold14.   

Abstract

BACKGROUND: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait.
OBJECTIVE: The primary issue involves the question of whether there exists a mixed hypo or hyper-dopaminergia in this population.
METHOD: Genetic Addiction Risk Score (GARS®) testing was carried out of 24 Caucasians of ages 12-19, derived from families with RDS.
RESULTS: We have found that adolescents from this cohort, derived from RDS parents, displayed a high risk for any addictive behavior (a hypodopaminergia), especially, drug-seeking (95%) and alcohol-seeking (64%).
CONCLUSION: The adolescents in our study, although more work is required, show a hypodopaminergic trait, derived from a family with Reward Deficiency Syndrome (RDS). Certainly, in future studies, we will analyze GARS in non-RDS Caucasians between the ages of 12-19. The suggestion is first to identify risk alleles with the GARS test and, then, use well-researched precision, pro-dopamine neutraceutical regulation. This "two-hit" approach might prevent tragic fatalities among adolescents, in the face of the American opioid/psychostimulant epidemic.

Entities:  

Keywords:  Adolescents; Genetic Addiction Risk Score (GARS); Precision Addiction Management (PAM); hyperdopaminergia; hypodopaminergia; meso-limbic system; prefrontal cortex

Year:  2021        PMID: 34707969      PMCID: PMC8547282          DOI: 10.2174/2211556010666210215155509

Source DB:  PubMed          Journal:  Curr Psychopharmacol        ISSN: 2211-5560


  47 in total

1.  Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism.

Authors:  E P Noble; K Blum; T Ritchie; A Montgomery; P J Sheridan
Journal:  Arch Gen Psychiatry       Date:  1991-07

2.  [3H]naloxone binding in the human brain: alcoholism and the TaqI A D2 dopamine receptor polymorphism.

Authors:  T Ritchie; E P Noble
Journal:  Brain Res       Date:  1996-04-29       Impact factor: 3.252

3.  Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

Authors:  Kenneth Blum; Edward J Modestino; Rajendra D Badgaiyan; David Baron; Panayotis K Thanos; Igor Elman; David Siwicki; Marcelo Febo; Mark S Gold
Journal:  EC Psychol Psychiatr       Date:  2018-07-30

4.  Weight gain is associated with reduced striatal response to palatable food.

Authors:  Eric Stice; Sonja Yokum; Kenneth Blum; Cara Bohon
Journal:  J Neurosci       Date:  2010-09-29       Impact factor: 6.167

Review 5.  The D2 dopamine receptor gene as a determinant of reward deficiency syndrome.

Authors:  K Blum; P J Sheridan; R C Wood; E R Braverman; T J Chen; J G Cull; D E Comings
Journal:  J R Soc Med       Date:  1996-07       Impact factor: 18.000

6.  Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress.

Authors:  Matthew A Weber; Eric T Graack; Jamie L Scholl; Kenneth J Renner; Gina L Forster; Michael J Watt
Journal:  Eur J Neurosci       Date:  2018-07-10       Impact factor: 3.386

7.  Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress.

Authors:  Andrew M Novick; Gina L Forster; James E Hassell; Daniel R Davies; Jamie L Scholl; Kenneth J Renner; Michael J Watt
Journal:  Neuropharmacology       Date:  2015-06-06       Impact factor: 5.250

8.  High and low doses of cocaine intake are differentially regulated by dopamine D2 receptors in the ventral tegmental area and the nucleus accumbens.

Authors:  R Chen; S McIntosh; S E Hemby; H Sun; T Sexton; T J Martin; S R Childers
Journal:  Neurosci Lett       Date:  2018-02-14       Impact factor: 3.046

Review 9.  Developmental imaging genetics: linking dopamine function to adolescent behavior.

Authors:  Aarthi Padmanabhan; Beatriz Luna
Journal:  Brain Cogn       Date:  2013-10-17       Impact factor: 2.310

Review 10.  Neuropharmacological and Neurogenetic Correlates of Opioid Use Disorder (OUD) As a Function of Ethnicity: Relevance to Precision Addiction Medicine.

Authors:  Tomilowo Abijo; Kenneth Blum; Marjorie C Gondré-Lewis
Journal:  Curr Neuropharmacol       Date:  2020       Impact factor: 7.363

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  3 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.  Proposing a "Brain Health Checkup (BHC)" as a Global Potential "Standard of Care" to Overcome Reward Dysregulation in Primary Care Medicine: Coupling Genetic Risk Testing and Induction of "Dopamine Homeostasis".

Authors:  Eric R Braverman; Catherine A Dennen; Mark S Gold; Abdalla Bowirrat; Ashim Gupta; David Baron; A Kenison Roy; David E Smith; Jean Lud Cadet; Kenneth Blum
Journal:  Int J Environ Res Public Health       Date:  2022-04-30       Impact factor: 4.614

Review 3.  Prenatal Effects of Nicotine on Obesity Risks: A Narrative Review.

Authors:  Olivia White; Nicole Roeder; Kenneth Blum; Rina D Eiden; Panayotis K Thanos
Journal:  Int J Environ Res Public Health       Date:  2022-08-02       Impact factor: 4.614

  3 in total

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