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

doi:10.1016/j.jns.2023.120809

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

J Neurol Sci. 2023 Oct 15:453:120809. doi: 10.1016/j.jns.2023.120809. Epub 2023 Sep 23.

Authors

Kenneth Blum¹, J Wesson Ashford², Babak Kateb³, Daniel Sipple⁴, Eric Braverman⁵, Catherine A Dennen⁶, David Baron⁷, Rajendra Badgaiyan⁸, Igor Elman⁹, Jean Lud Cadet¹⁰, Panayotis K Thanos¹¹, Colin Hanna¹¹, Abdalla Bowirrat¹², Edward J Modestino¹³, Vicky Yamamoto¹⁴, Ashim Gupta¹⁵, Thomas McLaughlin¹⁶, Mlan Makale¹⁷, Mark S Gold¹⁸

Affiliations

¹ Division of Addiction Research & Education, Center for Exercise, Sports and Mental Health, Western University Health Sciences, Pomona, CA, USA; The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX, USA; Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel. Electronic address: drd2gene@gmail.com.
² Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA; War Related Illness & Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA, USA.
³ Brain Mapping Foundation, Los Angeles, CA, USA; National Center for Nanobioelectronic, Los Angeles, CA, USA; Brain Technology and Innovation Park, Los Angeles, CA, USA.
⁴ Midwest Brain & Spine Institute, Roseville, MS, USA.
⁵ The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX, USA.
⁶ Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA.
⁷ Division of Addiction Research & Education, Center for Exercise, Sports and Mental Health, Western University Health Sciences, Pomona, CA, USA.
⁸ Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, San Antonio, TX, USA; Long School of Medicine, University of Texas Medical Center, San Antonio, TX, USA.
⁹ Center for Pain and the Brain (PAIN Group), Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children's Hospital, Waltham, MA, USA; Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.
¹⁰ Molecular Neuropsychiatry Research Branch, NIH National Institute on Drug Abuse, Bethesda, MD, USA.
¹¹ Department of Psychology & Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, USA.
¹² Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel.
¹³ Department of Psychology, Curry College, Milton, MA, USA.
¹⁴ Brain Mapping Foundation, Los Angeles, CA, USA; National Center for Nanobioelectronic, Los Angeles, CA, USA; Brain Technology and Innovation Park, Los Angeles, CA, USA; Society for Brain Mapping and Therapeutics, Los Angeles, CA, USA; USC-Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
¹⁵ Future Biologics, Lawrenceville, GA, USA.
¹⁶ Division of Reward Deficiency Research, Reward Deficiency Syndrome Clinics of America, Austin, TX, USA.
¹⁷ Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
¹⁸ Department of Psychiatry, Washington College of Medicine, St. Louis, MO, USA.

PMID: 37774561
DOI: 10.1016/j.jns.2023.120809

Abstract

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.

Keywords: Brain check; Dopamine homeostasis; Epigenetic insults; Gene guided therapy; Genetic addiction severity; Hypodopamineism; Neurophysiological.