Dopaminergic dysfunction: Role for genetic & epigenetic testing in the new psychiatry

Kenneth Blum, J. Wesson Ashford, Babak Kateb, Daniel Sipple, Eric Braverman, Catherine A. Dennen, David Baron, Rajendra Badgaiyan, Igor Elman, Jean Lud Cadet, Panayotis K. Thanos, Colin Hanna, Abdalla Bowirrat, Edward J. Modestino, Vicky Yamamoto, Ashim Gupta, Thomas McLaughlin, Mlan Makale, Mark S. Gold

Research output: Contribution to journalArticlepeer-review


Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.2 million) of individuals living in the US aged 12 or older had used illicit drugs in the past year. However, only 1.5% (4.1 million) of these individuals had received any substance use treatment. This increase in use and failure to adequately treat or provide treatment to these individuals resulted in 106,699 overdose deaths in 2021 and increased in 2022. This article presents an alternative non-pharmaceutical treatment approach tied to gene-guided therapy, the subject of many decades of research. The cornerstone of this paradigm shift is the brain reward circuitry, brain stem physiology, and neurotransmitter deficits due to the effects of genetic and epigenetic insults on the interrelated cascade of neurotransmission and the net release of dopamine at the Ventral Tegmental Area -Nucleus Accumbens (VTA-NAc) reward site. The Genetic Addiction Risk Severity (GARS) test and pro-dopamine regulator nutraceutical KB220 were combined to induce “dopamine homeostasis” across the brain reward circuitry. This article aims to encourage four future actionable items: 1) the neurophysiologically accurate designation of, for example, “Hyperdopameism /Hyperdopameism” to replace the blaming nomenclature like alcoholism; 2) encouraging continued research into the nature of dysfunctional brainstem neurotransmitters across the brain reward circuitry; 3) early identification of people at risk for all RDS behaviors as a brain check (cognitive testing); 4) induction of dopamine homeostasis using “precision behavioral management” along with the coupling of GARS and precision Kb220 variants; 5) utilization of promising potential treatments include neuromodulating modalities such as Transmagnetic stimulation (TMS) and Deep Brain Stimulation(DBS), which target different areas of the neural circuitry involved in addiction and even neuroimmune agents like N-acetyl-cysteine.

Original languageEnglish (US)
Article number120809
JournalJournal of the Neurological Sciences
StatePublished - Oct 15 2023


  • Brain check
  • Dopamine homeostasis
  • Epigenetic insults
  • Gene guided therapy
  • Genetic addiction severity
  • Hypodopamineism
  • Neurophysiological

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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