Search Results (18)

Background: In the United States, approximately 1 in 5 children experience comorbidities with mental illness, including depression and anxiety, which lead to poor general health outcomes. Adolescents with substance use disorders exhibit high rates of co-occurring mental illness, with over 60% meeting diagnostic criteria for another psychiatric condition in community-based treatment programs. Comorbidities are influenced by both genetic (DNA antecedents) and environmental (epigenetic) factors. Given the significant impact of psychiatric comorbidities on individuals’ lives, this study aims to uncover common mechanisms through a Genome-Wide Association Study (GWAS) meta-meta-analysis. Methods: GWAS datasets were obtained for each comorbid phenotype, followed by a GWAS meta-meta-analysis using a significance threshold of p < 5E−8 to validate the rationale behind combining all GWAS phenotypes. The combined and refined dataset was subjected to bioinformatic analyses, including Protein–Protein Interactions and Systems Biology. Pharmacogenomics (PGx) annotations for all potential genes with at least one PGx were tested, and the genes identified were combined with the Genetic Addiction Risk Severity (GARS) test, which included 10 genes and eleven Single Nucleotide Polymorphisms (SNPs). The STRING-MODEL was employed to discover novel networks and Protein–Drug interactions. Results: Autism Spectrum Disorder (ASD) was identified as the top manifestation derived from the known comorbid interaction of anxiety, depression, and attention deficit hyperactivity disorder (ADHD). The STRING-MODEL and Protein–Drug interaction analysis revealed a novel network associated with these psychiatric comorbidities. The findings suggest that these interactions are linked to the need to induce “dopamine homeostasis” as a therapeutic outcome. Conclusions: This study provides a reliable genetic and epigenetic map that could assist healthcare professionals in the therapeutic care of patients presenting with multiple psychiatric manifestations, including anxiety, depression, and ADHD. The results highlight the importance of targeting dopamine homeostasis in managing ASD linked to these comorbidities. These insights may guide future pharmacogenomic interventions to improve clinical outcomes in affected individuals. Full article

It is predicted that by 2030, globally, an estimated 2.16 billion adults will be overweight, and 1.12 billion will be obese. This study examined genetic data regarding Reward Deficiency Syndrome (RDS) to evaluate their usefulness in counselling patients undergoing bariatric surgery and gathered preliminary data on the potential use in predicting short term (6-month) weight loss outcomes. Methods: Patients undergoing bariatric surgery (n = 34) were examined for Genetic Addiction Risk Severity (GARS) [measures the presence of risk alleles associated with RDS]; as well as their psychosocial traits (questionnaires). BMI changes and sociodemographic data were abstracted from Electronic Health Records. Results: Subjects showed ∆BMI (M = 10.0 ± 1.05 kg/m²) and a mean % excess weight loss (56 ± 13.8%). In addition, 76% of subjects had GARS scores above seven. The homozygote risk alleles for MAO (rs768062321) and DRD1 (rs4532) showed a 38% and 47% prevalence among the subjects. Of the 11 risk alleles identified by GARS, the DRD4 risk allele (rs1800955), was significantly correlated with change in weight and BMI six months post-surgery. We identified correlations with individual risk alleles and psychosocial trait scores. The COMT risk allele (rs4680) showed a negative correlation with EEI scores (r = −0.4983, p < 0.05) and PSQI scores (r = −0.5482, p < 0.05). The GABRB3 risk allele (rs764926719) correlated positively with EEI (r = 0.6161, p < 0.01) and FCQ scores (r = 0.6373, p < 0.01). The OPRM1 risk allele showed a positive correlation with the DERS score (r = 0.5228, p < 0.05). We also identified correlations between DERS and BMI change (r = 0.61; p < 0.01). Conclusions: These data support the potential benefit of a personalized medicinal approach inclusive of genetic testing and psychosocial trait questionnaires when counselling patients with obesity considering bariatric surgery. Future research will explore epigenetic factors that contribute to outcomes of bariatric surgery. Full article

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

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 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

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

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

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

Cannabis is one of the most commonly used and abused illicit drugs in the world today. The United States (US) currently has the highest annual prevalence rate of cannabis consumption in the world, 17.9% in individuals aged 12 or older, and it is on the rise. With increasing cannabis use comes the potential for an increase in abuse, and according to the Substance Abuse and Mental Health Services Administration (SAMHSA), approximately 5.1% of Americans had Cannabis Use Disorder (CUD) in 2020. Research has shown that genetics and epigenetics play a significant role in cannabis use and CUD. In fact, approximately 50–70% of liability to CUD and 40–48% of cannabis use initiation have been found to be the result of genetic factors. Cannabis usage and CUD have also been linked to an increased risk of psychiatric disorders and Reward Deficiency Syndrome (RDS) subsets like schizophrenia, depression, anxiety, and substance use disorder. Comprehension of the genetic and epigenetic aspects of cannabinoids is necessary for future research, treatment plans, and the production of pure cannabinoid compounds, which will be essential for FDA approval. In conclusion, having a better understanding of the epigenetic and genetic underpinnings of cannabis use, CUD, and the endocannabinoid system as a whole will aid in the development of effective FDA-approved treatment therapies and the advancement of personalized medicine. Full article

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 brief commentary aims to provide an overview of the available and relatively new precision management of reward deficiencies manifested as substance and behavioral disorders. Current and future advances, concepts, and the substantial evidential basis of this potential therapeutic and prophylactic treatment modality are presented. Precision Behavioral Management (PBM), conceptualized initially as Precision Addiction Management (PAM), certainly deserves consideration as an important modality for the treatment of impaired cognitive control in reward processing as manifested in people with neurobiologically expressed Reward Deficiency Syndrome (RDS). Full article

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

In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some pain clinicians seem to prefer classical analgesic agents that promote unwanted tolerance to analgesics and subsequent biological induction of the “addictive brain”. Reward genes play a vital part in modulation of nociception and adaptations in the dopaminergic circuitry. They may affect various sensory and affective components of the chronic pain syndromes. The Genetic Addiction Risk Severity (GARS) test coupled with the H-Wave at entry in pain clinics could attenuate pain and help prevent addiction. The GARS test results identify high-risk for both drug and alcohol, and H-Wave can be initiated to treat pain instead of opioids. The utilization of H-Wave to aid in pain reduction and mitigation of hedonic addictive behaviors is recommended, notwithstanding required randomized control studies. This frontline approach would reduce the possibility of long-term neurobiological deficits and fatalities associated with potent opioid analgesics. Full article

Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e., a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent JAMA report indicates that non-opioid treatments fare better than chronic opioid treatments. Research demonstrates that over 50 percent of all suicides are related to alcohol or other drug use. In addition to effective fellowship programs and spirituality acceptance, nutrigenomic therapies (e.g., KB220Z) optimize gene expression, rebalance neurotransmitters, and restore neurotransmitter functional connectivity. KB220Z was shown to increase functional connectivity across specific brain regions involved in dopaminergic function. KB220/Z significantly reduces RDS behavioral disorders and relapse in human DUI offenders. Taking a Genetic Addiction Risk Severity (GARS) test combined with a the KB220Z semi-customized nutrigenomic supplement effectively restores dopamine homeostasis (WC 199). Full article

Background: The United States Centers for Disease Control and Prevention (CDC) estimates a total obesity rate of 30% for 12 states and a 20% obesity rate nationwide. The obesity epidemic continues to increase in spite of preventative measures undertaken worldwide. Pharmacological treatments promise to reduce total fat mass. However, medications may have significant side effects and can be potentially fatal. Data Retrieval: This brief review, based on a PUBMED search of the key terms “Obesity” and” Sarcopenia,” will present evidence to corroborate the existence of Reward Deficiency Syndrome (RDS) in obesity and the involvement of catecholaminergic pathways in substance seeking behavior, particularly as it relates to carbohydrates cravings. Expert Opinion: The genetic basis and future genetic testing of children for risk of aberrant generalized craving behavior are considered a prevention method. Here we present evidence supporting the use of precursor amino acid therapy and modulation of enkephalinase, MOA, and COMT inhibition in key brain regions. Such treatments manifest in improved levels of dopamine/norepinephrine, GABA, serotonin, and enkephalins. We also present evidence substantiating insulin sensitivity enhancement via Chromium salts, which affect dopamine neuronal synthesis regulation. We believe our unique combination of natural ingredients will influence many pathways leading to the promotion of well-being and normal healthy metabolic functioning. Sarcopenia has been shown to reduce angiogenesis and possible cerebral blood flow. Exercise seems to provide a significant benefit to overcome this obesity-promoting loss of muscle density. Conclusion: Utilization of proposed nutrigenomic formulae based on coupling genetic obesity risk testing promotes generalized anti-craving of carbohydrates and can inhibit carbohydrate bingeing, inducing significant healthy fat loss and relapse prevention. Full article