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Personalized Molecular Neurobiology of Brain Mapping of Global Pain and...
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Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 44884

Special Issue Editors

Prof. Dr. Kenneth Blum

E-Mail Website
Guest Editor
1. Division of Nutrigenomics, SpliceGen, Therapeutics, Inc., Austin, TX 78701, USA
2. Department of Psychiatry, Wright State University Boonshoft School of Medicine, Dayton, OH 45435, USA
3. Division of Addiction Research & Education, Center for Sports, Exercise, & Mental Health, Western University Health Sciences, Pomona, CA 91766, USA
4. Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel
5. Division of Personalized Pain Therapy Research & Education, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA
6. The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA

Interests: addiction research; personalized medicine; genetic factors influencing addiction and behavioral disorders employing nutrigenomics and epigenetics; addiction recovery; pain therapy; mental health
Special Issues, Collections and Topics in MDPI journals
Dr. Babak Kateb

E-Mail Website
Guest Editor
Society for Brain Mapping and Therapeutics, Los Angeles, CA 90272, USA
Interests: brain mapping
Dr. Vicky Yamamoto

E-Mail Website
Guest Editor
Keck School of Medicine of USC, Department of Biochemistry and Molecular Biology, Los Angeles, CA, USA
Interests: developmental neurobiology; brain mapping; stem cell; molecular targeted therapy; head and neck surgery
Prof. Dr. Igor Elman

E-Mail Website
Guest Editor
Department of Psychiatry, School of Medicine, Harvard University, Cambridge, MA 02142, USA
Interests: addiction medicine; stress system; pathophysiology of severe neuropsychiatric disorders; psychiatry
Special Issues, Collections and Topics in MDPI journals
Dr. Mark S. Gold

E-Mail Website
Guest Editor
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
Interests: translational addiction neuroscience
Special Issues, Collections and Topics in MDPI journals
Dr. Kai-Uwe Lewandrowski

E-Mail Website
Guest Editor
1. Division of Personalized Pain Therapy Research & Education, Center for Advanced Spine Care of Southern Arizona, 4787 E Camp Lowell Drive, Tucson, AZ 85712, USA
2. Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá 111321, Colombia
3. Department of Orthopedics, Hospital Universitário Gaffre e Guinle, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil
Interests: spinal surgery; spinal disorders; thoracic and lumbar spine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The special issue is initiated by the Brain Mapping Society (www.WorldBrainMapping.Org).

Background & history of this topic:

The disease model of all mental illnesses has resulted in an exhaustive neurobiological and neurogenetic literature involving thousands of peer reviewed studies. Sadly, worldwide mental health statistics show that the prevalence of mental illnesses has increased significantly over the past decade. One of the reasons for the rise in the number of mental health issues is the stigma and lack of awareness and support surrounding mental health problems. With more and more people battling symptoms and signs of mental issues, and coronavirus wreaking havoc, it is essential that as scientists and clinicians worldwide, in the spirit of sharing our unique knowledge across all related disciplines and psychopathologies, we encourage submissions to this Special Issue. Table 1 represents the unfortunate facts related to mental illness in 2021.

Table 1. 2021 Mental Illness facts.
  • Over 970 million people globally have some form of mental illness
  • Only 2% of the overall health budget goes towards mental health treatment.
  • In America, 1 in 5 adults suffers from a mental illness, but around 60% of them do not receive treatment.
  • It’s not uncommon for depression to occur with another illness or medical condition.
  • 83% of bipolar disorder patients have a severe case.
  • Young people from the LGBTQ+ population are 2.5 times more likely to experience symptoms of depression or anxiety or have problems with substance abuse.
  • Mental illness statistics in the USA show that 56% of Americans do not receive mental health treatment when they need it, often because they do not have access to mental healthcare.
  • In 2018, police officers shot and killed 987 people in the US, around 245 of whom had serious mental health issues.
  • 14.9% of children aged 4 and under whose parents had poor mental health develop a disorder themselves. 
  • Women are more likely to experience depression during their lifetimes than men.
  • It’s possible for a patient to suffer from both depression and schizophrenia.
  • Mental health disorders are more prevalent than cancer, diabetes, or heart disease.
  • 34% of people from Gen Z stated that their mental health worsened during the pandemic.
  • 48 million Americans have some type of anxiety disorder.
  • 10.8% of Americans with mental illnesses do not have any health insurance.
  • The DSM-5 lists over 200 forms of mental illnesses.

We appreciate the fact that Mental health disorders are complex and can take many forms. While some controversy still exists, the underlying source of the worldwide data presented is typically in accordance with the WHO’s International Classification of Diseases (ICD-10). This broad definition incorporates many forms, including depression, anxiety, bipolar, eating disorders, and schizophrenia. Importantly, the Global Burden of Disease study aggregates substance use disorders (alcohol and drug use disorders) with mental health disorders in many statistics. It is also becoming clear that even non-substance behavioral addictions (e.g. gambling, over-eating, eating disorders, internet and smart phone seeking), have been shown to have similar neurobiological and genomic overlap with typical SUDs.  The current literature demonstrates that mental health disorders are common everywhere.

Aim and scope of the Special Issue:

AIM

Improving the awareness, recognition, support, and treatment of this range of disorders should be an essential focus of global health. As a result, it is the aim and scope of this Special Issue.

SCOPE

Along these lines, it is noteworthy that the highest rate of imprisonment has been marked in the states with the least access to mental health care and poor mental health awareness, such as Alabama, Arkansas, and Texas. Accordingly, these states also have higher incarceration rates overall. Those imprisoned who also suffer from mental health problems usually first became involved with the law through minor offenses such as disorderly conduct. High levels of poverty and poor physical health are probably the main contributing factors when it comes to these shocking statistics.

In addition, it is now known that Schizophrenia, a notably severe mental health condition, is characterized by disturbances in reasoning and emotions and an overall twisted perception of reality. The data suggest that this chronic condition is quite widespread in Australia (with around 150,000–200,000 patients suffering from it). However, it is relatively rare worldwide, according to most facts about schizophrenia.

Despite the misconceptions of those who lack accurate information on mental health disorders, there is no correlation between mental illnesses and character flaws. It is indeed prudent to point out that although children are not the most common sufferers of mental disorders, they do experience mental problems, and it happens more frequently than people may assume. Due to the misconception that children cannot become depressed, anxious, schizophrenic, etc., many of them are misdiagnosed or their state is considered typical childish behavior.

In May 2019, the World Health Organization announced that being transgender would no longer be classified as a mental health issue as it had been defined under ICD-10. Under ICD-11, gender incongruence, or “a marked and persistent incongruence between a person’s experienced gender and assigned sex,” is no longer classified among the mental and behavioral disorders. Hopefully, this will have a positive impact on transgender mental health statistics, which in 2018 indicated that transgender people have a four-fold increased risk of depression.

Our goal is to promote the advancement of the science and knowledge surrounding pain issues, unwanted problems related to both substance and non-substance addictions, and all mental health-related illnesses to benefit society and improve lives. 

Cutting-edge research:

From a scientific perspective, global mental health statistics suggest that there is more to mental illness than merely having too much or too little of certain chemicals in the brain resulting in impaired neurotransmitter signaling in, for example, the brain reward circuitry. Certainly, there is overlap or co-occurrence of addictive behaviors. There are other factors that contribute: stress, upbringing, genetic vulnerability, other medical conditions, etc. Cutting edge research related to the neurobiological and genetic etiological roots of all mental health will especially resonate as being an important topic to address in this Special Issue.

It is also important to perform cutting-edge research on addiction medicine. Addiction scientists and clinicians face an incredible challenge in combatting the current opioid and alcohol use disorder (AUD) pandemic worldwide. Significant progress has been made; however, the death toll from narcotic overdose reached 100,000 fatalities in the United States alone in 2021. The National Institute on Drug Abuse (NIDA) and The National Institute on Alcohol Abuse and Alcoholism (NIAAA) continue to struggle with the generation of novel approaches to combat the severity of the current substance abuse epidemic. Specifically, world data in 2017 revealed that for alcohol use disorder there were 107 million people afflicted and for SUD (excluding alcohol) there were 71 million.

Non-cancerous pain treatment is challenging for primary care medicine. By 2014, an NIH survey estimated that 25.3 million adults had pain every day for the preceding 3 months. In 2016–2017, many thousands of people died from opiate/opioid overdoses, especially the synthetic opioid fentanyl, which is more than 50 times more potent than other prescription opioids. To combat this growing threat to public safety, in 2016 new guidelines for prescribing opioids to chronic pain patients were issued by the Center for Disease Control (CDC). Morphine milligram equivalents declined by 29% in 2017, but more than 64,000 people still died from narcotic overdoses, leading to a decrease in national life expectancy. Currently, nearly 116 million Americans suffer from chronic pain, according to the National Institute on Drug Abuse (NIDA). Those who suffer from severe pain are also likely to have worse overall physical and mental health status.

What kind of papers we are soliciting:

Understanding the need to overcome this terrible global crisis, we the editors, along with the staff of the Journal of Precision Medicine, which is prestigious and PUBMED INDEXED with an official impact factor of 4.95. We hereby encourage high quality articles related to neurobiology, genomics, and clinical research. While we are reaching out to the scientific community at large, each submission will undergo rigorous peer review to help guide the final published product. Each accepted submission will be open access, with a one-time charge of 1,007 USD to cover costs, which is a 50% discount off the regular article processing fee.  The type of manuscripts we are looking for include editorials, perspectives, original research, and systematic reviews. There are no limitations to the number of authors. A minimum wordcount of 3000 per article is a journal requirement. The deadline for submission is November 30th 2022 at 5 PM USA Eastern Standard Time.

We are interested in a wide range of topics, including (but not limited to) the following:

women’s issues; men’s issues; abuse and violence; addictive disorders; reward deficiency; cannabis use disorder; ADHD; ADD; Tourette’s; autism; adjustment disorder; adolescents; aging issues; alcohol use and abuse; Alzheimer’s disease; anger; anxiety disorders; attachment issues; bipolar disorder; bullying; children issues; conduct disorders; conflict resolution; major depression; dissociative  disorders; drug use and abuse; eating disorders; family issues; grief and loss; HIV/AIDS; learning issues; PTSD; schizophrenia; personality disorders; obesity; obsessive compulsive disorder (OCD); pain management; panic disorder; parenting issues; suicide and self-harm; phobias; schizophrenia; sexual disorders; sleep issues; spirituality; stress; and trauma.

Please join us by submitting your important work and be part of the caring community of scientists across the globe working tirelessly to overcome the suffering of unfortunate victims.

Prof. Dr. Kenneth Blum
Dr. Babak Kateb
Dr. Vicky Yamamoto 
Prof. Dr. Igor Elman
Dr. Mark S. Gold
Dr. Kai-Uwe Lewandrowski 
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • personalized medicine
  • molecular neurobiology
  • brain mapping
  • global pain
  • addiction and mental illness
  • reward processing
  • brain reward circuitry
  • induction of dopamine homeostasis
  • genomics
  • neurotransmitters

Published Papers (16 papers)

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Editorial

Jump to: Research, Review, Other

6 pages, 832 KiB  
Editorial
Role of microRNA-132 in Opioid Addiction through Modification of Neural Stem Cell Differentiation
by Anne-Marie Fauser, Emily Stidham, Craig Cady and Ashim Gupta
J. Pers. Med. 2022, 12(11), 1800; https://doi.org/10.3390/jpm12111800 - 01 Nov 2022
Viewed by 1125
Abstract
In this editorial, we focused on the article, “MicroRNA-132 in the Adult Dentate Gyrus is Involved in Opioid Addiction Via Modifying the Differentiation of Neural Stem Cells” by Jia and colleagues [...] Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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Research

Jump to: Editorial, Review, Other

17 pages, 1279 KiB  
Communication
Genetic Addiction Risk Severity Assessment Identifies Polymorphic Reward Genes as Antecedents to Reward Deficiency Syndrome (RDS) Hypodopaminergia’s Effect on Addictive and Non-Addictive Behaviors in a Nuclear Family
by Catherine A. Dennen, Kenneth Blum, Abdalla Bowirrat, Panayotis K. Thanos, Igor Elman, Mauro Ceccanti, Rajendra D. Badgaiyan, Thomas McLaughlin, Ashim Gupta, Anish Bajaj, David Baron, B. William Downs, Debasis Bagchi and Mark S. Gold
J. Pers. Med. 2022, 12(11), 1864; https://doi.org/10.3390/jpm12111864 - 08 Nov 2022
Cited by 2 | Viewed by 2375
Abstract
This case series presents the novel genetic addiction risk score (GARS), which shows a high prevalence of polymorphic risk alleles of reward genes in a nuclear family with multiple reward deficiency syndrome (RDS) behavioral issues expressing a hypodopaminergic antecedent. The family consists of [...] Read more.
This case series presents the novel genetic addiction risk score (GARS), which shows a high prevalence of polymorphic risk alleles of reward genes in a nuclear family with multiple reward deficiency syndrome (RDS) behavioral issues expressing a hypodopaminergic antecedent. The family consists of a mother, father, son, and daughter. The mother experienced issues with focus, memory, anger, and amotivational syndrome. The father experienced weight issues and depression. The son experienced heavy drinking, along with some drug abuse and anxiety. The daughter experienced depression, lethargy, brain fog, focus issues, and anxiety, among others. A major clinical outcome of the results presented to the family members helped reduce personal guilt and augment potential hope for future healing. Our laboratory’s prior research established that carriers of four or more alleles measured by GARS (DRD1-DRD4, DAT1, MOR, GABABR3, COMT, MAOAA, and 5HTLPR) are predictive of the addiction severity index (ASI) for drug abuse, and carriers of seven or more alleles are predictive of severe alcoholism. This generational case series shows the impact that genetic information has on reducing stigma and guilt in a nuclear family struggling with RDS behaviors. The futuristic plan is to introduce an appropriate DNA-guided “pro-dopamine regulator” into the recovery and enhancement of life. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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22 pages, 2081 KiB  
Communication
Genetic Addiction Risk and Psychological Profiling Analyses for “Preaddiction” Severity Index
by Kenneth Blum, David Han, Abdalla Bowirrat, Bernard William Downs, Debasis Bagchi, Panayotis K. Thanos, David Baron, Eric R. Braverman, Catherine A. Dennen, Ashim Gupta, Igor Elman, Rajendra D. Badgaiyan, Luis Llanos-Gomez, Jag Khalsa, Debmalya Barh, Thomas McLaughlin and Mark S. Gold
J. Pers. Med. 2022, 12(11), 1772; https://doi.org/10.3390/jpm12111772 - 27 Oct 2022
Cited by 5 | Viewed by 2754
Abstract
Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those [...] Read more.
Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those at risk for at least alcohol use disorder (AUD), a subset of reward deficiency syndrome (RDS), Blum’s group developed the genetic addiction risk severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions, including pain and even bariatric surgery, as a predictor of severe vulnerability to unwanted addictive behaviors, published since 1990 until now. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. Pearson’s χ2 test or Fisher’s exact test was applied to compare the gender, genotype, and allele distribution if available. The statistical analyses found the OR, 95% CI for OR, and the post risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. Prior to these results, the United States and European patents on a ten gene panel and eleven risk alleles have been issued. In the face of the new construct of the “preaddiction” model, similar to “prediabetes”, the genetic addiction risk analysis might provide one solution missing in the treatment and prevention of the neurological disorder known as RDS. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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10 pages, 389 KiB  
Article
Job-Related Performance and Quality of Life Benefits in First Responders Given Access to H-Wave® Device Stimulation: A Retrospective Cohort Study
by Tyler K. Williamson, Hugo C. Rodriguez, David Han, Stephen M. Norwood and Ashim Gupta
J. Pers. Med. 2022, 12(10), 1674; https://doi.org/10.3390/jpm12101674 - 08 Oct 2022
Cited by 5 | Viewed by 1189
Abstract
Current chronic pain treatments primarily target symptoms and are often associated with harmful side-effects and complications, while safer non-invasive electrotherapies like H-Wave® device stimulation (HWDS) have been less explored. The goal of this study is to evaluate first responder-reported effects of HWDS [...] Read more.
Current chronic pain treatments primarily target symptoms and are often associated with harmful side-effects and complications, while safer non-invasive electrotherapies like H-Wave® device stimulation (HWDS) have been less explored. The goal of this study is to evaluate first responder-reported effects of HWDS on job-related and quality-of-life measures. This is a retrospective cohort study where first responders were surveyed following voluntary use of HWDS regarding participant experience, frequency of use, job-related performance, and quality-of-life. Responses were analyzed using means comparison tests, while bivariate analysis assessed responses associated with HWDS usage. Overall, 92.9% of first responder HWDS users (26/28) reported a positive experience (p < 0.0001), with 82.1% citing pain reduction (p = 0.0013), while 78.6% indicated it would be beneficial to have future device access (p = 0.0046). Participants using H-Wave® were at least six times more likely to report higher rates of benefit (100% vs. 0%, p = 0.022), including pain reduction (91.3% vs. 8.7%, p = 0.021) and improved range-of-motion (93.3% vs. 69.2%, p = 0.044). Spending more time with family was associated with better job performance following frequent HWDS use (50% vs. 8.3%, p = 0.032). Repetitive first responder H-Wave® use, with minimal side effects and easy utilization, resulted in significant pain reduction, improvements in job performance and range-of-motion, and increased time spent with family, resulting in overall positive experiences and health benefits. Level of Evidence: III. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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13 pages, 934 KiB  
Article
Statistical Validation of Risk Alleles in Genetic Addiction Risk Severity (GARS) Test: Early Identification of Risk for Alcohol Use Disorder (AUD) in 74,566 Case–Control Subjects
by Kenneth Blum, David Han, Ashim Gupta, David Baron, Eric R. Braverman, Catherine A. Dennen, Shan Kazmi, Luis Llanos-Gomez, Rajendra D. Badgaiyan, Igor Elman, Panayotis K. Thanos, Bill W. Downs, Debasis Bagchi, Marjorie C. Gondre-Lewis, Mark S. Gold and Abdalla Bowirrat
J. Pers. Med. 2022, 12(9), 1385; https://doi.org/10.3390/jpm12091385 - 26 Aug 2022
Cited by 9 | Viewed by 2115
Abstract
Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk [...] Read more.
Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum’s group developed the Genetic Addiction Risk Severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. If available, the Pearson’s χ2 test or Fisher’s exact test was applied to comparisons of the gender, genotype, and allele distribution. The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. The OR results showed significance for DRD2, DRD3, DRD4, DAT1, COMT, OPRM1, and 5HTT at 5%. While most of the research related to GARS is derived from our laboratory, we are encouraging more independent research to confirm our findings. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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25 pages, 3151 KiB  
Article
A Proposed Personalized Spine Care Protocol (SpineScreen) to Treat Visualized Pain Generators: An Illustrative Study Comparing Clinical Outcomes and Postoperative Reoperations between Targeted Endoscopic Lumbar Decompression Surgery, Minimally Invasive TLIF and Open Laminectomy
by Kai-Uwe Lewandrowski, Ivo Abraham, Jorge Felipe Ramírez León, Albert E. Telfeian, Morgan P. Lorio, Stefan Hellinger, Martin Knight, Paulo Sérgio Teixeira De Carvalho, Max Rogério Freitas Ramos, Álvaro Dowling, Manuel Rodriguez Garcia, Fauziyya Muhammad, Namath Hussain, Vicky Yamamoto, Babak Kateb and Anthony Yeung
J. Pers. Med. 2022, 12(7), 1065; https://doi.org/10.3390/jpm12071065 - 29 Jun 2022
Cited by 2 | Viewed by 2909
Abstract
Background: Endoscopically visualized spine surgery has become an essential tool that aids in identifying and treating anatomical spine pathologies that are not well demonstrated by traditional advanced imaging, including MRI. These pathologies may be visualized during endoscopic lumbar decompression (ELD) and categorized into [...] Read more.
Background: Endoscopically visualized spine surgery has become an essential tool that aids in identifying and treating anatomical spine pathologies that are not well demonstrated by traditional advanced imaging, including MRI. These pathologies may be visualized during endoscopic lumbar decompression (ELD) and categorized into primary pain generators (PPG). Identifying these PPGs provides crucial information for a successful outcome with ELD and forms the basis for our proposed personalized spine care protocol (SpineScreen). Methods: a prospective study of 412 patients from 7 endoscopic practices consisting of 207 (50.2%) males and 205 (49.8%) females with an average age of 63.67 years and an average follow-up of 69.27 months was performed to compare the durability of targeted ELD based on validated primary pain generators versus image-based open lumbar laminectomy, and minimally invasive lumbar transforaminal interbody fusion (TLIF) using Kaplan-Meier median survival calculations. The serial time was determined as the interval between index surgery and when patients were censored for additional interventional and surgical treatments for low back-related symptoms. A control group was recruited from patients referred for a surgical consultation but declined interventional and surgical treatment and continued on medical care. Control group patients were censored when they crossed over into any surgical or interventional treatment group. Results: of the 412 study patients, 206 underwent ELD (50.0%), 61 laminectomy (14.8%), and 78 (18.9%) TLIF. There were 67 patients in the control group (16.3% of 412 patients). The most common surgical levels were L4/5 (41.3%), L5/S1 (25.0%), and L4-S1 (16.3%). At two-year f/u, excellent and good Macnab outcomes were reported by 346 of the 412 study patients (84.0%). The VAS leg pain score reduction was 4.250 ± 1.691 (p < 0.001). No other treatment during the available follow-up was required in 60.7% (125/206) of the ELD, 39.9% (31/78) of the TLIF, and 19.7% (12/61 of the laminectomy patients. In control patients, only 15 of the 67 (22.4%) control patients continued with conservative care until final follow-up, all of which had fair and poor functional Macnab outcomes. In patients with Excellent Macnab outcomes, the median durability was 62 months in ELD, 43 in TLIF, and 31 months in laminectomy patients (p < 0.001). The overall survival time in control patients was eight months with a standard error of 0.942, a lower boundary of 6.154, and an upper boundary of 9.846 months. In patients with excellent Macnab outcomes, the median durability was 62 months in ELD, 43 in TLIF, and 31 months in laminectomy patients versus control patients at seven months (p < 0.001). The most common new-onset symptom for censoring was dysesthesia ELD (9.4%; 20/206), axial back pain in TLIF (25.6%;20/78), and recurrent pain in laminectomy (65.6%; 40/61) patients (p < 0.001). Transforaminal epidural steroid injections were tried in 11.7% (24/206) of ELD, 23.1% (18/78) of TLIF, and 36.1% (22/61) of the laminectomy patients. The secondary fusion rate among ELD patients was 8.8% (18/206). Among TLIF patients, the most common additional treatments were revision fusion (19.2%; 15/78) and multilevel rhizotomy (10.3%; 8/78). Common follow-up procedures in laminectomy patients included revision laminectomy (16.4%; 10/61), revision ELD (11.5%; 7/61), and multilevel rhizotomy (11.5%; 7/61). Control patients crossed over into ELD (13.4%), TLIF (13.4%), laminectomy (10.4%) and interventional treatment (40.3%) arms at high rates. Most control patients treated with spinal injections (55.5%) had excellent and good functional outcomes versus 40.7% with fair and poor (3.7%), respectively. The control patients (93.3%) who remained in medical management without surgery or interventional care (14/67) had the worst functional outcomes and were rated as fair and poor. Conclusions: clinical outcomes were more favorable with lumbar surgeries than with non-surgical control groups. Of the control patients, the crossover rate into interventional and surgical care was 40.3% and 37.2%, respectively. There are longer symptom-free intervals after targeted ELD than with TLIF or laminectomy. Additional intervention and surgical treatments are more often needed to manage new-onset postoperative symptoms in TLIF- and laminectomy compared to ELD patients. Few ELD patients will require fusion in the future. Considering the rising cost of surgical spine care, we offer SpineScreen as a simplified and less costly alternative to traditional image-based care models by focusing on primary pain generators rather than image-based criteria derived from the preoperative lumbar MRI scan. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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13 pages, 2740 KiB  
Article
STAT3 and NTRK2 Genes Predicted by the Bioinformatics Approach May Play Important Roles in the Pathogenesis of Multiple Sclerosis and Obsessive–Compulsive Disorder
by Ali Sepehrinezhad, Ali Shahbazi, Ali Bozorgmehr, Babak Kateb, Vicky Yamamoto and Sajad Sahab Negah
J. Pers. Med. 2022, 12(7), 1043; https://doi.org/10.3390/jpm12071043 - 26 Jun 2022
Cited by 2 | Viewed by 1718
Abstract
Background: There are no data available on the levels of genetic networks between obsessive–compulsive disorder (OCD) and multiple sclerosis (MS). To this point, we aimed to investigate common mechanisms and pathways using bioinformatics approaches to find novel genes that may be involved in [...] Read more.
Background: There are no data available on the levels of genetic networks between obsessive–compulsive disorder (OCD) and multiple sclerosis (MS). To this point, we aimed to investigate common mechanisms and pathways using bioinformatics approaches to find novel genes that may be involved in the pathogenesis of OCD in MS. Methods: To obtain gene–gene interactions for MS and OCD, the STRING database was used. Cytoscape was then used to reconstruct and visualize graphs. Then, ToppGene and Enrichr were used to identify the main pathological processes and pathways involved in MS-OCD novel genes. Additionally, to predict transcription factors and microRNAs (miRNAs), the Enrichr database and miRDB database were used, respectively. Results: Our bioinformatics analysis showed that the signal transducer and the activator of transcription 3 (STAT3) and neurotrophic receptor tyrosine kinase 2 (NTRK2) genes had connections with 32 shared genes between MS and OCD. Furthermore, STAT3 and NTRK2 had the greatest enrichment parameters (i.e., molecular function, cellular components, and signaling pathways) among ten hub genes. Conclusions: To summarize, data from our bioinformatics analysis showed that there was a significant overlap in the genetic components of MS and OCD. The findings from this study make two contributions to future studies. First, predicted mechanisms related to STAT3 and NTRK2 in the context of MS and OCD can be investigated for pharmacological interventions. Second, predicted miRNAs related to STAT3 and NTRK2 can be tested as biomarkers in MS with OCD comorbidity. However, our study involved bioinformatics research; therefore, considerable experimental work (e.g., postmortem studies, case–control studies, and cohort studies) will need to be conducted to determine the etiology of OCD in MS from a mechanistic view. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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13 pages, 1578 KiB  
Article
Brain Mapping the Effects of Chronic Aerobic Exercise in the Rat Brain Using FDG PET
by Colin Hanna, John Hamilton, Eliz Arnavut, Kenneth Blum and Panayotis K. Thanos
J. Pers. Med. 2022, 12(6), 860; https://doi.org/10.3390/jpm12060860 - 25 May 2022
Cited by 6 | Viewed by 2385
Abstract
Exercise is a key component to health and wellness and is thought to play an important role in brain activity. Changes in brain activity after exercise have been observed through various neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission [...] Read more.
Exercise is a key component to health and wellness and is thought to play an important role in brain activity. Changes in brain activity after exercise have been observed through various neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). The precise impact of exercise on brain glucose metabolism (BGluM) is still unclear; however, results from PET studies seem to indicate an increase in regional metabolism in areas related to cognition and memory, direction, drive, motor functions, perception, and somatosensory areas in humans. Using PET and the glucose analog [18F]-Fluorodeoxyglucose (18F-FDG), we assessed the changes in BGluM between sedentary and chronic exercise in rats. Chronic treadmill exercise treatment demonstrated a significant increase in BGluM activity in the following brain regions: the caudate putamen (striatum), external capsule, internal capsule, deep cerebellar white matter, primary auditory cortex, forceps major of the corpus callosum, postsubiculum, subiculum transition area, and the central nucleus of the inferior colliculus. These brain regions are functionally associated with auditory processing, memory, motor function, and motivated behavior. Therefore, chronic daily treadmill running in rats stimulates BGluM in distinct brain regions. This identified functional circuit provides a map of brain regions for future molecular assessment which will help us understand the biomarkers involved in specific brain regions following exercise training, as this is critical in exploring the therapeutic potential of exercise in the treatment of neurodegenerative disease, traumatic brain injury, and addiction. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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21 pages, 398 KiB  
Article
FOXN3 and GDNF Polymorphisms as Common Genetic Factors of Substance Use and Addictive Behaviors
by Andrea Vereczkei, Csaba Barta, Anna Magi, Judit Farkas, Andrea Eisinger, Orsolya Király, Andrea Belik, Mark D. Griffiths, Anna Szekely, Mária Sasvári-Székely, Róbert Urbán, Marc N. Potenza, Rajendra D. Badgaiyan, Kenneth Blum, Zsolt Demetrovics and Eszter Kotyuk
J. Pers. Med. 2022, 12(5), 690; https://doi.org/10.3390/jpm12050690 - 26 Apr 2022
Cited by 10 | Viewed by 4644
Abstract
Epidemiological and phenomenological studies suggest shared underpinnings between multiple addictive behaviors. The present genetic association study was conducted as part of the Psychological and Genetic Factors of Addictions study (n = 3003) and aimed to investigate genetic overlaps between different substance use, [...] Read more.
Epidemiological and phenomenological studies suggest shared underpinnings between multiple addictive behaviors. The present genetic association study was conducted as part of the Psychological and Genetic Factors of Addictions study (n = 3003) and aimed to investigate genetic overlaps between different substance use, addictive, and other compulsive behaviors. Association analyses targeted 32 single-nucleotide polymorphisms, potentially addictive substances (alcohol, tobacco, cannabis, and other drugs), and potentially addictive or compulsive behaviors (internet use, gaming, social networking site use, gambling, exercise, hair-pulling, and eating). Analyses revealed 29 nominally significant associations, from which, nine survived an FDRbl correction. Four associations were observed between FOXN3 rs759364 and potentially addictive behaviors: rs759364 showed an association with the frequency of alcohol consumption and mean scores of scales assessing internet addiction, gaming disorder, and exercise addiction. Significant associations were found between GDNF rs1549250, rs2973033, CNR1 rs806380, DRD2/ANKK1 rs1800497 variants, and the “lifetime other drugs” variable. These suggested that genetic factors may contribute similarly to specific substance use and addictive behaviors. Specifically, FOXN3 rs759364 and GDNF rs1549250 and rs2973033 may constitute genetic risk factors for multiple addictive behaviors. Due to limitations (e.g., convenience sampling, lack of structured scales for substance use), further studies are needed. Functional correlates and mechanisms underlying these relationships should also be investigated. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)

Review

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23 pages, 4429 KiB  
Review
Future Newborns with Opioid-Induced Neonatal Abstinence Syndrome (NAS) Could Be Assessed with the Genetic Addiction Risk Severity (GARS) Test and Potentially Treated Using Precision Amino-Acid Enkephalinase Inhibition Therapy (KB220) as a Frontline Modality Instead of Potent Opioids
by Mauro Ceccanti, Kenneth Blum, Abdalla Bowirrat, Catherine A. Dennen, Eric R. Braverman, David Baron, Thomas Mclaughlin, John Giordano, Ashim Gupta, Bernard W. Downs, Debasis Bagchi, Debmalya Barh, Igor Elman, Panayotis K. Thanos, Rajendra D. Badgaiyan, Drew Edwards and Mark S. Gold
J. Pers. Med. 2022, 12(12), 2015; https://doi.org/10.3390/jpm12122015 - 06 Dec 2022
Cited by 2 | Viewed by 2618
Abstract
In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of [...] Read more.
In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn–parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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Other

16 pages, 2403 KiB  
Case Report
Positive Clinical Outcomes for Severe Reported Pain Using Robust Non-Addictive Home Electrotherapy—A Case-Series
by Anish Bajaj, David Han, Igor Elman, Panayotis K. Thanos, Catherine A. Dennen, Rajendra D. Badgaiyan, Abdalla Bowirrat, Debmalya Barh and Kenneth Blum
J. Pers. Med. 2023, 13(2), 336; https://doi.org/10.3390/jpm13020336 - 15 Feb 2023
Cited by 1 | Viewed by 1551
Abstract
The North American opioid epidemic has resulted in over 800,000 related premature overdose fatalities since 2000, with the United States leading the world in highest opioid deaths per capita. Despite increased federal funding in recent years, intended to address this crisis, opioid overdose [...] Read more.
The North American opioid epidemic has resulted in over 800,000 related premature overdose fatalities since 2000, with the United States leading the world in highest opioid deaths per capita. Despite increased federal funding in recent years, intended to address this crisis, opioid overdose mortality has continued to increase. Legally prescribed opioids also chronically induce a problematic reduction in affect. While an ideal analgesic has yet to be developed, some effective multimodal non-opioid pharmacological regimens for acute pain management are being more widely utilized. Some investigators have suggested that a safer and more scientifically sound approach might be to induce “dopamine homeostasis” through non-pharmacological approaches, since opioid use even for acute pain of short duration is now being strongly questioned. There is also increasing evidence suggesting that some more robust forms of electrotherapy could be applied as an effective adjunct to avoid the problems associated with opioids. This 4-patient case-series presents such an approach to treatment of severe pain. All 4 of these chiropractic treatment cases involved a component of knee osteoarthritis, in addition to other reported areas of pain. Each patient engaged in a home recovery strategy using H-Wave® device stimulation (HWDS) to address residual extremity issues following treatment of spinal subluxation and other standard treatments. A simple statistical analysis was conducted to determine the change in pain scores (Visual Analogue Scale) of pre and post electrotherapy treatments, resulting in significant reductions in self-reported pain (p-value = 0.0002). Three of the four patients continued using the home therapy device long-term as determined by a post-analysis questionnaire. This small case-series demonstrated notably positive outcomes, suggesting consideration of home use of HWDS for safe, non-pharmacological and non-addictive treatment of severe pain. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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20 pages, 2076 KiB  
Commentary
Theorizing the Role of Dopaminergic Polymorphic Risk Alleles with Intermittent Explosive Disorder (IED), Violent/Aggressive Behavior and Addiction: Justification of Genetic Addiction Risk Severity (GARS) Testing
by Edward Justin Modestino, Kenneth Blum, Catherine A. Dennen, B. William Downs, Debasis Bagchi, Luis Llanos-Gomez, Igor Elman, David Baron, Panayotis K. Thanos, Rajendra D. Badgaiyan, Eric R. Braverman, Ashim Gupta, Mark S. Gold and Abdalla Bowirrat
J. Pers. Med. 2022, 12(12), 1946; https://doi.org/10.3390/jpm12121946 - 23 Nov 2022
Cited by 2 | Viewed by 2644
Abstract
Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In [...] Read more.
Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In our previous research, we examined the Taq A1 allele (variant D2 dopamine receptor gene) and the DAT-40 base repeat (a variant of the dopamine transporter gene) in 11 Caucasian boys at the Brown School in San Marcus, Texas, diagnosed with intermittent explosive disorder. Thirty supernormal controls were screened to exclude several reward–deficit behaviors, including pathological violence, and genotyped for the DRD2 gene. Additionally, 91 controls were screened to exclude ADHD, pathological violence, alcoholism, drug dependence, and tobacco abuse, and their results were compared with DAT1 genotype results. In the schoolboys vs. supercontrols, there was a significant association with the D2 variant and a trend with the dopamine transporter variant. Results support our hypothesis and the involvement of at least two gene risk alleles with adolescent violent/aggressive behaviors. This study and the research presented in this paper suggest that violent/aggressive behaviors are associated with a greater risk of addiction, mediated via various genes linked to the BRC. This review provides a contributory analysis of how gene polymorphisms, especially those related to the brain reward circuitry, are associated with violent behaviors. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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16 pages, 1174 KiB  
Commentary
Should Reward Deficiency Syndrome (RDS) Be Considered an Umbrella Disorder for Mental Illness and Associated Genetic and Epigenetic Induced Dysregulation of Brain Reward Circuitry?
by Kenneth Blum, Catherine A. Dennen, Igor Elman, Abdalla Bowirrat, Panayotis K. Thanos, Rajendra D. Badgaiyan, B. William Downs, Debasis Bagchi, David Baron, Eric R. Braverman, Ashim Gupta, Richard Green, Thomas McLaughlin, Debmalya Barh and Mark S. Gold
J. Pers. Med. 2022, 12(10), 1719; https://doi.org/10.3390/jpm12101719 - 14 Oct 2022
Cited by 8 | Viewed by 3334
Abstract
Reward Deficiency Syndrome (RDS) is defined as a breakdown of reward neurotransmission that results in a wide range of addictive, compulsive, and impulsive behaviors. RDS is caused by a combination of environmental (epigenetic) influences and DNA-based (genetic) neurotransmission deficits that interfere with the [...] Read more.
Reward Deficiency Syndrome (RDS) is defined as a breakdown of reward neurotransmission that results in a wide range of addictive, compulsive, and impulsive behaviors. RDS is caused by a combination of environmental (epigenetic) influences and DNA-based (genetic) neurotransmission deficits that interfere with the normal satisfaction of human physiological drives (i.e., food, water, and sex). An essential feature of RDS is the lack of integration between perception, cognition, and emotions that occurs because of (1) significant dopaminergic surges in motivation, reward, and learning centers causing neuroplasticity in the striato-thalamic-frontal cortical loop; (2) hypo-functionality of the excitatory glutamatergic afferents from the amygdala–hippocampus complex. A large volume of literature regarding the known neurogenetic and psychological underpinnings of RDS has revealed a significant risk of dopaminergic gene polymorphic allele overlap between cohorts of depression and subsets of schizophrenia. The suggestion is that instead of alcohol, opioids, gambling disorders, etc. being endophenotypes, the true phenotype is RDS. Additionally, reward deficiency can result from depleted or hereditary hypodopaminergia, which can manifest as a variety of personality traits and mental/medical disorders that have been linked to genetic studies with dopamine-depleting alleles. The carrying of known DNA antecedents, including epigenetic insults, results in a life-long vulnerability to RDS conditions and addictive behaviors. Epigenetic repair of hypodopaminergia, the causative basis of addictive behaviors, may involve precision DNA-guided therapy achieved by combining the Genetic Addiction Risk Severity (GARS) test with a researched neutraceutical having a number of variant names, including KB220Z. This nutraceutical formulation with pro-dopamine regulatory capabilities has been studied and published in peer-reviewed journals, mostly from our laboratory. Finally, it is our opinion that RDS should be given an ICD code and deserves to be included in the DSM-VI because while the DSM features symptomology, it is equally important to feature etiological roots as portrayed in the RDS model. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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18 pages, 1705 KiB  
Case Report
DNA Directed Pro-Dopamine Regulation Coupling Subluxation Repair, H-Wave® and Other Neurobiologically Based Modalities to Address Complexities of Chronic Pain in a Female Diagnosed with Reward Deficiency Syndrome (RDS): Emergence of Induction of “Dopamine Homeostasis” in the Face of the Opioid Crisis
by Anish Bajaj, Kenneth Blum, Abdalla Bowirrat, Ashim Gupta, David Baron, David Fugel, Ayo Nicholson, Taylor Fitch, B. William Downs, Debasis Bagchi, Catherine A. Dennen and Rajendra D. Badgaiyan
J. Pers. Med. 2022, 12(9), 1416; https://doi.org/10.3390/jpm12091416 - 30 Aug 2022
Cited by 3 | Viewed by 2191
Abstract
Addiction is a complex multifactorial condition. Established genetic factors can provide clear guidance in assessing the risk of addiction to substances and behaviors. Chronic stress can accumulate, forming difficult to recognize addiction patterns from both genetic and epigenetic (environmental) factors. Furthermore, psychological/physical/chemical stressors [...] Read more.
Addiction is a complex multifactorial condition. Established genetic factors can provide clear guidance in assessing the risk of addiction to substances and behaviors. Chronic stress can accumulate, forming difficult to recognize addiction patterns from both genetic and epigenetic (environmental) factors. Furthermore, psychological/physical/chemical stressors are typically categorized linearly, delaying identification and treatment. The patient in this case report is a Caucasian female, aged 36, who presented with chronic pain and partial disability following a surgically repaired trimalleolar fracture. The patient had a history of unresolved attention deficit disorder and an MRI scan of her brain revealed atrophy and functional asymmetry. In 2018, the patient entered the Bajaj Chiropractic Clinic, where initial treatment focused on re-establishing integrity of the spine and lower extremity biomechanics and graduated into cognitive behavior stabilization assisted by DNA pro-dopamine regulation guided by Genetic Addiction Risk Severity testing. During treatment (2018–2021), progress achieved included: improved cognitive clarity, focus, sleep, anxiety, and emotional stability in addition to pain reduction (75%); elimination of powerful analgesics; and reduced intake of previously unaddressed alcoholism. To help reduce hedonic addictive behaviors and pain, coupling of H-Wave with corrective chiropractic care seems prudent. We emphasize the importance of genetic assessment along with attempts at inducing required dopaminergic homeostasis via precision KB220PAM. It is hypothesized that from preventive care models, a new standard is emerging including self-awareness and accountability for reward deficiency as a function of hypodopaminergia. This case study documents the progression of a patient dealing with the complexities of an injury, pain management, cognitive impairment, anxiety, depression, and the application of universal health principles towards correction versus palliative care. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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13 pages, 832 KiB  
Commentary
Researching Mitigation of Alcohol Binge Drinking in Polydrug Abuse: KCNK13 and RASGRF2 Gene(s) Risk Polymorphisms Coupled with Genetic Addiction Risk Severity (GARS) Guiding Precision Pro-Dopamine Regulation
by Kenneth Blum, Mark S. Brodie, Subhash C. Pandey, Jean Lud Cadet, Ashim Gupta, Igor Elman, Panayotis K. Thanos, Marjorie C. Gondre-Lewis, David Baron, Shan Kazmi, Abdalla Bowirrat, Marcelo Febo, Rajendra D. Badgaiyan, Eric R. Braverman, Catherine A. Dennen and Mark S. Gold
J. Pers. Med. 2022, 12(6), 1009; https://doi.org/10.3390/jpm12061009 - 20 Jun 2022
Cited by 6 | Viewed by 2296
Abstract
Excessive alcohol intake, e.g., binge drinking, is a serious and mounting public health problem in the United States and throughout the world. Hence the need for novel insights into the underlying neurobiology that may help improve prevention and therapeutic strategies. Therefore, our group [...] Read more.
Excessive alcohol intake, e.g., binge drinking, is a serious and mounting public health problem in the United States and throughout the world. Hence the need for novel insights into the underlying neurobiology that may help improve prevention and therapeutic strategies. Therefore, our group employed a darkness-induced alcohol intake protocol to define the reward deficiency domains of alcohol and other substance use disorders in terms of reward pathways’ reduced dopamine signaling and its restoration via specifically-designed therapeutic compounds. It has been determined that KCNK13 and RASGRF2 genes, respectively, code for potassium two pore domain channel subfamily K member 13 and Ras-specific guanine nucleotide-releasing factor 2, and both genes have important dopamine-related functions pertaining to alcohol binge drinking. We present a hypothesis that identification of KCNK13 and RASGRF2 genes’ risk polymorphism, coupled with genetic addiction risk score (GARS)-guided precision pro-dopamine regulation, will mitigate binge alcohol drinking. Accordingly, we review published reports on the benefits of this unique approach and provide data on favorable outcomes for both binge-drinking animals and drunk drivers, including reductions in alcohol intake and prevention of relapse to drinking behavior. Since driving under the influence of alcohol often leads to incarceration rather than rehabilitation, there is converging evidence to support the utilization of GARS with or without KCNK13 and RASGRF2 risk polymorphism in the legal arena, whereby the argument that “determinism” overrides the “free will” account may be a plausible defense strategy. Obviously, this type of research is tantamount to helping resolve a major problem related to polydrug abuse. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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18 pages, 1533 KiB  
Perspective
Reward Deficiency Syndrome (RDS) Surprisingly Is Evolutionary and Found Everywhere: Is It “Blowin’ in the Wind”?
by Kenneth Blum, Thomas McLaughlin, Abdalla Bowirrat, Edward J. Modestino, David Baron, Luis Llanos Gomez, Mauro Ceccanti, Eric R. Braverman, Panayotis K. Thanos, Jean Lud Cadet, Igor Elman, Rajendra D. Badgaiyan, Rehan Jalali, Richard Green, Thomas A. Simpatico, Ashim Gupta and Mark S. Gold
J. Pers. Med. 2022, 12(2), 321; https://doi.org/10.3390/jpm12020321 - 21 Feb 2022
Cited by 18 | Viewed by 7186
Abstract
Reward Deficiency Syndrome (RDS) encompasses many mental health disorders, including a wide range of addictions and compulsive and impulsive behaviors. Described as an octopus of behavioral dysfunction, RDS refers to abnormal behavior caused by a breakdown of the cascade of reward in neurotransmission [...] Read more.
Reward Deficiency Syndrome (RDS) encompasses many mental health disorders, including a wide range of addictions and compulsive and impulsive behaviors. Described as an octopus of behavioral dysfunction, RDS refers to abnormal behavior caused by a breakdown of the cascade of reward in neurotransmission due to genetic and epigenetic influences. The resultant reward neurotransmission deficiencies interfere with the pleasure derived from satisfying powerful human physiological drives. Epigenetic repair may be possible with precision gene-guided therapy using formulations of KB220, a nutraceutical that has demonstrated pro-dopamine regulatory function in animal and human neuroimaging and clinical trials. Recently, large GWAS studies have revealed a significant dopaminergic gene risk polymorphic allele overlap between depressed and schizophrenic cohorts. A large volume of literature has also identified ADHD, PTSD, and spectrum disorders as having the known neurogenetic and psychological underpinnings of RDS. The hypothesis is that the true phenotype is RDS, and behavioral disorders are endophenotypes. Is it logical to wonder if RDS exists everywhere? Although complex, “the answer is blowin’ in the wind,” and rather than intangible, RDS may be foundational in species evolution and survival, with an array of many neurotransmitters and polymorphic loci influencing behavioral functionality. Full article
(This article belongs to the Special Issue Personalized Molecular Neurobiology of Brain Mapping of Global Pain and Mental Illness)
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