Lucid Dreams are a form of dream life, during which the dreamer may be aware that he/she is dreaming, can stop/re-start the dreams, depending on the pleasantness or unpleasant nature of the dream, and experiences the dream as if he/she were fully awake. Depending on their content, they may be pleasant, un-pleasant or terrifying, at least in the context of patients, who also exhibit characteristics of Reward Deficiency Syndrome (RDS) and Posttraumatic Stress Disorder (PTSD).
We present eight clinical cases, with known substance abuse, childhood abuse and diagnosed PTSD/RDS. The administration of a putative dopamine agonist, KB200Z™, was associated with the elimination of unpleasant and/or terrifying, lucid dreams in 87.5% of the cases presented, whereas one very heavy cocaine abuser showed a minimal response. These results required the continuous use of this nutraceutical. The lucid dreams themselves were distinguishable from typical, PTSD nightmares insofar as their content did not appear to reflect a symbolic rendition of an originally-experienced, historical trauma. Each of the cases was diagnosed with a form of RDS, i.e., ADHD, ADD, and/or Tourette’s syndrome. They all also suffered from some form of Post-Traumatic-Stress-Disorder (PTSD) and other psychiatric diagnoses as well.
The reduction or elimination of terrifying Lucid Dreams seemed to be dependent on KB220Z, whereby voluntary stopping of the agent results in reinstatement of the terrifying non-pleasant nature of the dreams. Following more required research on a much larger population we anticipate confirmation of these seemingly interesting observations. If these results in a small number of patients are indeed confirmed we may have found a frontline solution to a very perplexing and complicated symptom known as lucid dreams.
Putative natural dopamine agonist; KB200Z; Functional brain connectivity; Lucid dreams; Nightmares; PTSD
It is unclear whether pharmacotherapy for opioid use disorder (OUD) should be continued for short or long-term. Before introduction of buprenorphine, methadone was the primary pharmacotherapy for OUD in the United States. Because of its specific pharmacokinetic properties methadone was recommended for long-term use with some justification. Introduction of buprenorphine however has altered the treatment protocol because of milder adverse effects and withdrawal symptoms. The adverse effects of buprenorphine are milder but not negligible. Therefore, indefinite prescription is justified only if there is a significant benefit. Studies that have compared short and long-term treatment of buprenorphine protocols do not show a significant benefit of long-term treatment over relatively short-term (few months) treatment protocols. Obviously, the ultra short-term treatment lasting a few days has very little or no benefit on long-term treatment of buprenorphine protocols that use buprenorphine for 3 to 9 months is comparable to that of the long-term (years to lifetime) treatment without financial and medical consequences of the long-term treatment.
Pharmacotherapy; Opioid Use Disorder (OUD); Buprenorphine/naloxone; Mood changes
The connection between religion/spirituality and deviance, like substance abuse, was first made by Durkheim who defined socially expected behaviors as norms. He explained that deviance is due in large part to their absence (called anomie), and concluded that spirituality lowers deviance by preserving norms and social bonds. Impairments in brain reward circuitry, as observed in Reward Deficiency Syndrome (RDS), may also result in deviance and as such we wondered if stronger belief in spirituality practice and religious belief could lower relapse from drugs of abuse.
The NIDA Drug Addiction Treatment Outcome Study data set was used to examine post hoc relapse rates among 2,947 clients who were interviewed at 12 months after intake broken down by five spirituality measures.
Our main findings strongly indicate, that those with low spirituality have higher relapse rates and those with high spirituality have higher remission rates with crack use being the sole exception. We found significant differences in terms of cocaine, heroin, alcohol, and marijuana relapse as a function of strength of religious beliefs (x2 = 15.18, p = 0.028; logistic regression = 10.65, p = 0.006); frequency of attending religious services (x2 = 40.78, p < 0.0005; logistic regression = 30.45, p < 0.0005); frequency of reading religious books (x2 = 27.190, p < 0.0005; logistic regression = 17.31, p < 0.0005); frequency of watching religious programs (x2 = 19.02, p = 0.002; logistic regression = ns); and frequency of meditation/prayer (x2 = 11.33, p = 0.045; logistic regression = 9.650, p = 0.002). Across the five measures of spirituality, the spiritual participants reported between 7% and 21% less alcohol, cocaine, heroin, and marijuana use than the non-spiritual subjects. However, the crack users who reported that religion was not important reported significantly less crack use than the spiritual participants. The strongest association between remission and spirituality involves attending religious services weekly, the one marker of the five that involves the highest social interaction/social bonding consistent with Durkheim’s social bond theory.
Stronger spiritual/religious beliefs and practices are directly associated with remission from abused drugs except crack. Much like the value of having a sponsor, for clients who abuse drugs, regular spiritual practice, particularly weekly attendance at the religious services of their choice is associated with significantly higher remission. These results demonstrate the clinically significant role of spirituality and the social bonds it creates in drug treatment programs.
Relapse; Neurogentics; Reward Deficiency Syndrome (RDS); Spirituality; Genospirituality; Anomie; Social Bonds; Religion
The Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors or RDS, which was coined to define addictive behaviors and their genetic components.
To carry out this review we searched a number of important databases including: Filtered: Cochrane Systematic reviews; DARE; Pubmed Central Clinical Quaries; National Guideline Clearinghouse and unfiltered resources: PsychINFO; ACP PIER; PsychSage; Pubmed/Medline. The major search terms included: dopamine agonist therapy for Addiction; dopamine agonist therapy for Reward dependence; dopamine antagonistic therapy for addiction; dopamine antagonistic therapy for reward dependence and neurogenetics of RDS.
While there are many studies claiming a genetic association with RDS behavior, not all are scientifically accurate.
Albeit our bias, this Clinical Pearl discusses the facts and fictions behind molecular genetic testing in RDS and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™), the first test to accurately predict one’s genetic risk for RDS.
Reward Deficiency Syndrome; Brain Reward Cascade; DRD2; Gene variations; Genetic Addiction Risk Score
Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character.
We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid “bad dreams” remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares.
The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient’s regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter.
These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies.
putative complex dopamine agonist; KB220Z; parasomnia; functional brain connectivity; lucid nightmares; Post-Traumatic Stress Disorder (PTSD)
The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta- analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non- SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis.. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD.
schizophrenia; substance related disorders; dopaminergic; reward deficiency syndrome (RDS); gamma –endorphins
Cranial electrotherapy stimulation (CES) is a noninvasive therapy that has been used for decades in the United States to treat anxiety, depression, and insomnia in the general population. The effectiveness of CES has been questioned by many and its use is considered controversial. In this study we are presenting data on one alcoholic patient using a newly engineered device we call Neuro-Electro-Adaptive Therapy 12™ [NEAT12]. This hybrid device utilizes TENS current characteristics yielding CES effects. This device has been found to primarily target the excitation of the Cingulate Gyrus region of the brain.
This is a 42 year old male who has been abstinent from alcohol for approximately two months. The data presented herein represents the pre to post qEEG differences of an alcoholic in protracted abstinence. This subject was evaluated both before and after using the NEAT-12 device. The pre to post comparisons suggest that the cortical potentials especially at the Cingulate Gyrus are up regulated after using the device. The absolute power changes obtained shows a decrease of more than 2 SD as noted in the delta wave spectrum. Also noted is an overall cortical increase in the alpha spectrum. The resting alert state of a neuro typical population is most prominently marked by a regulation of 7.5-11 Hz alpha throughout the cortex. The decreased in delta and theta suggests an up regulation of the prefrontal cortex and the anterior Cingulate Gyrus a site involved in substance use disorder (SUD).
A presence of dominant slow waves through the prefrontal cortex and the anterior Cingulate Gyrus is often associated with OCD, anxiety, impulsivity and cravings in addicted populations. It is conceivable that our initial finding of altered electrical activity of the brain using qEEG analysis suggests the NEAT-12 may induce a “normalization” of aberrant electrical activity of the cortical region of the brain known to occur during protracted abstinence of alcoholics. It may have utility as a putative anti-craving CES device and therefore warrants intensive investigation.
There is a plethora of research indicating the successful treatment of opioid dependence with either buprenorphine alone or in combination with naloxone (Suboxone®). However, we encourage caution in long-term maintenance with these drugs, albeit, lack of any other FDA approved opioid maintenance compound to date. Our concern has been supported by severe withdrawal (even with tapering of the dosage of for example Suboxone® which is 40 times more potent than morphine) from low dose of buprenorphine (alone or with naloxone). In addition our findings of a long-term flat affect in chronic Suboxone® patients amongst other unwanted side effects including diversion and suicide attempts provides impetus to reconsider long-term utilization. However, it seems prudent to embrace genetic testing to reveal reward circuitry gene polymorphisms especially those related to dopaminergic pathways as well as opioid receptor(s) as a way of improving treatment outcomes. Understanding the interaction of reward circuitry involvement in buprenorphine effects and respective genotypes provide a novel framework to augment a patient's clinical experience and benefits during opioid replacement therapy.
Buprenorphine; Naloxone; Suboxone; Dopamine & Opioid polymorphic genes; Reward Deficiency Syndrome (RDS)
It is well-known that sleep has a vital function especially as it relates to prevention of substance-related disorders as discussed in the DSM-V. We are cognizant that certain dopaminergic gene polymorphisms have been associated with various sleep disorders. The importance of “normal dopamine homeostasis” is tantamount for quality of life especially for the recovering addict. Since it is now know that sleep per se has been linked with metabolic clearance of neurotoxins in the brain, it is parsonomiuos to encourage continued research in sleep science, which should ultimately result in attenuation of sleep deprivation especially associated with substance related disorders.
sleep; dopaminergic system; neurogenetics; metabolic clearance of neurotoxins; Reward Deficiency Syndrome (RDS)
Females develop multiple hormonal alterations and certain genes may be involved in the intensity of subsequent symptoms including both mood and drug seeking. Seventy Four (74) females were included (mean age=60.23, SD=9.21, [43-87]). A medical evaluation was completed with hormone screening using a number of statistical analyses such as Pearson product moment; one way ANOVA and Regression analysis along with a Bonferroni significance correction p<.004. Of 120 correlations performed, significant hormone/domain correlations were as follows: DHEA/Genitourinary (r=.30, p<.05); FSH/Pulmonary (r=−.29, p<.05); Pregnenolone/Genitourinary (r=.40, p<.006) /Immunological (r=.38, p<.008); Testosterone/total endorsed symptoms (r=−0.34, p<.016); TSH/Pulmonary (r=−.33, p<.03) /Gynecological (r=.30, p<.05). Estrone/Musculoskeletal (r=−0.43, p<.012). After a Bonferroni correction (experiment-wise p<.00045) for statistical significance, no hormones remained significance. In the follow–up phase FSH/Neuropsychiatric (r=.56, p<.05) and Musculoskeletal (r=.67, p<.013); DHEA/Immunological (r=.64, p<.04); LH/ Musculoskeletal (r=.59, p<.34); Free Testosterone/Neuropsychiatric (r=.64, p<.019), Musculoskeletal (r=.68, p<.01), and Dermatologic (r=.57, p<.04); Total Testosterone/Immunological (r=.63, p<.028); TSH/Endocrinological (r=−.62, p<.031). Factor analysis of the MQ yielded two factors with eigenvalues > 1.0 (high loadings: first: Pulmonary, GI, Cardiovascular, and Immunological; second: Musculoskeletal, Gynecological, and the three Neurological domains). Both factors had significant correlations: first/pregnenolone (r=.37, p<.019); second/TSH (r=.33, p<.034). An additional factor analysis of hormone level clusters showed significant correlations with various domains. This study highlights the need to test the core biological endocrine hormones associated with females. Future research will focus on the relationship of for example Leptin and the electrophysiology of the brain. We are cautiously proposing a new paradigm shift whereby we replace the old nomenclature of HRT to MHRT.
Female aging; Hormones; Women’s health; Two-factor analysis; HRT
Various studies have demonstrated that increased leptin levels and obesity are inversely related to cognitive decline in menopausal women. It is hypothesized that adiposity is inversely correlated with cognitive decline, as women with increased weight are less vulnerable to diminishing cognition. However, it is increasingly observed that menopausal women, even with increased adiposity, experience significant cognitive decline. Positron emission tomography (PET) has been used to analyze cognitive function and processing in menopausal women. Evoked potentials (P300) and neurophysiologic tests have validated brain metabolism in cognitively impaired patients. Post-hoc analyses of 796 female patients entering PATH Medical Clinic, between January 4, 2009 and February 24, 2013, were performed as part of the “Menopause Analytical Hormonal Correlate Outcome Study” (MAHCOS). Patient age range was 39–76 years (46.7±0.2). P300 latency and amplitude correlated with a number of hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, estrone, estriol, DHEA, pregnenolone, progesterone, free and total testosterone, thyroid stimulating hormone (TSH), Vitamins D 1.25 and D 25OH, leptin, and insulin-like growth factor-binding protein 3 (IGF-BP3). Corrected statistics did not reveal significant associations with P300 latency or amplitude for these hormones except for leptin plasma levels. However, factor analysis showed that FSH and LH clustered together with Vitamin D1.25 and Vitamin D25OH, P300 latency (not amplitude), and log leptin were found to be associated in the same cluster. Utilizing regression analysis, once age adjusted, leptin was the only significant predictor for latency or speed (p = 0.03) with an effect size of 0.23. Higher plasma leptin levels were associated with abnormal P300 speed (OR = 0.98). Our findings show a significant relationship of higher plasma leptin levels, potentially due to leptin resistance, and prolonged P300 latency. This suggests leptin resistance may delay electrophysiological processing of memory and attention, which appears to be the first of such an association.
This is the first quantitative analysis of data from urine drug tests for compliance to treatment medications and abstinence from drug abuse across “levels of care” in six eastern states of America. Comprehensive Analysis of Reported Drugs (CARD) data was used in this post-hoc retrospective observational study from 10,570 patients, filtered to include a total of 2,919 patients prescribed at least one treatment medication during 2010 and 2011. The first and last urine samples (5,838 specimens) were analyzed; compliance to treatment medications and abstinence from drugs of abuse supported treatment effectiveness for many. Compared to non-compliant patients, compliant patients were marginally less likely to abuse opioids, cannabinoids, and ethanol during treatment although more likely to abuse benzodiazepines. Almost 17% of the non-abstinent patients used benzodiazepines, 15% used opiates, and 10% used cocaine during treatment. Compliance was significantly higher in residential than in the non-residential treatment facilities. Independent of level of care, 67.2% of the patients (n = 1963; P<.001) had every treatment medication found in both first and last urine specimens (compliance). In addition, 39.2% of the patients (n = 1143; P<.001) had no substance of abuse detected in either the first or last urine samples (abstinence). Moreover, in 2010, 16.9% of the patients (n = 57) were abstinent at first but not at last urine (deteriorating abstinence), the percentage dropped to 13.3% (n = 174) in 2011; this improvement over years was statistically significant. A longitudinal analysis for abstinence and compliance was studied in a randomized subset from 2011, (n = 511) representing 17.5% of the total cohort. A statistically significant upward trend (p = 2.353×10−8) of abstinence rates as well as a similar but stronger trend for compliance ((p = 2.200×10−16) was found. Being cognizant of the trend toward drug urine testing being linked to medical necessity eliminating abusive screening, the interpretation of these valuable results require further intensive investigation.
Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment of the brain reward circuitry resulting in a hypo-dopaminergic function. RDS involves the interactions of powerful neurotransmitters and results in abnormal craving behavior. A number of important facts which could help translate to potential therapeutic targets espoused in this focused review include: (1) consumption of alcohol in large quantities or carbohydrates binging stimulates the brain’s production of and utilization of dopamine; (2) in the meso-limbic system the enkephalinergic neurons are in close proximity, to glucose receptors; (3) highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; (4) a significant correlation between blood glucose and cerebrospinal fluid concentrations of homovanillic acid the dopamine metabolite; (5) 2-deoxyglucose (2DG), the glucose analog, in pharmacological doses is associated with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and fMRI in humans support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and for the most part, implicate the involvement of DA-modulated reward circuits in pathologic eating behaviors. Based on a consensus of neuroscience research treatment of both glucose and drug like cocaine, opiates should incorporate dopamine agonist therapy in contrast to current theories and practices that utilizes dopamine antagonistic therapy. Considering that up until now clinical utilization of powerful dopamine D2 agonists have failed due to chronic down regulation of D2 receptors newer targets based on novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of reward deficiency.
obesity; glucose craving; dopamine release; glucoprivation; neurogentics; reward deficiency syndrome
Background: Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors. Methods: This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline. Results: A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits. Discussion: Importantly, the proposal is that the real phenotype is RDS and impairments in the brain’s reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have “hatched the behavioral addiction egg”, we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of “redeeming joy” and permitting homo sapiens live a life, free of addiction and pain.
neurogenetics; epigenetics; dopaminergic; Reward Deficiency Syndrome; dopamine agonist therapy
While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes.
Understanding the role of neurotransmission in the prefrontal cortex and mesolimbic brain regions has become the subject of intensive neuroscience research worldwide. In the 1970s, our group provided evidence that rats exposed to darkness significantly augmented their alcohol intake. At that time, we proposed that melatonin was the culprit. At around the same time, our laboratory, amongst a few others, proposed that dopamine-adducts with acetaldehyde to induce alcohol intake both in rodents and in humans. While the work in these areas has declined considerably over the years, more recent scientifically sound studies continue to show the importance of these earlier controversial ideas involving alcohol abuse and alcoholism. A review of the literature has provided impetus to systematically access the newer genetic and molecular neurobiological findings relevant to the physiological and psychological motives for high alcohol consumption in animals and humans alike. Thus, we hypothesize that darkness-induced alcohol intake is linked not only to serotonergic-melatonin mechanisms, but also to dopaminergic regulation of brain mesolimbic pathways involving neuronal expression switching in response to long photoperiods affecting gene expression.
Photoperiod; alcohol intake; dopamine; reward pathway; serotonin and melatonin; nocturnal
Substance use disorders (SUD) are inheritable and the culprit is hypodopaminergic function regulated by reward genes. We evaluated a natural dopaminergic agonist; KB220 intravenous (IV) and oral variants, to improve dopaminergic function in SUD. Our pilot experiment found a significant reduction of chronic symptoms, measured by the Chronic Abstinence Symptom Severity (CASS) Scale. The combined group (IV and oral) did significantly better than the oral-only group over the first week and 30-day follow-up period. Next, the combination was given to129 subjects and three factors; Emotion, Somatic, and Impaired Cognition, with eigenvalues greater than one were extracted for baseline CASS-Revised (CASS-R) variables. Paired sample t-tests for pre and post-treatment scales showed significant declines (p = .00001) from pre- to post-treatment: t = 19.1 for Emotion, t = 16.1 for Somatic, and t = 14.9 for Impaired Cognition. In a two-year follow-up of 23 subjects who underwent KB220IV therapy (at least five IV treatments over seven days) plus orals for 30+ days: 21 (91%) were sober at six months, 19 (82%) having no relapse; 19 (82%) were sober at one year, 18 (78%) having no relapse; and 21 (91%) were sober two-years post-treatment, 16 (70%) having no relapse. We await additional research and advise caution in interpreting these encouraging results.
Chronic Abstinence Symptom Severity (CASS) Scale; dopamine; KB220IV-neuroadaptagen amino-acid therapy (NAAT); reward deficiency syndrome (RDS)
Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor self-esteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with > 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches.
genetics; attention deficit/hyperactivity disorder; diagnosis; treatment; legal aspects of testing
Addictions to smoking, alcohol, illicit drugs, and certain behaviors like gambling, overeating, and sex, are prevalent worldwide. These behaviors are highly destructive and costly to individuals and society due to health consequences, criminality and lost productivity. The genetic vulnerability, environmental exposures, and individual behaviors that contribute to the brain dysfunction and compulsive tendencies that mark addiction make it one of the most complicated diseases to study and treat. Although much has been learned about the genetic basis of and biochemical imbalances associated with the addictions, research leading to effective treatments has been slow. Addictions are often accompanied by an inner sense of disintegration, enslavement and meaninglessness that can be viewed in terms of a spiritual craving for wholeness, freedom, and transformation. Arguably, progress towards effective treatment has been retarded by insufficient attention being paid to understanding the role of spirituality in helping to heal addicts. Assuming one accepts the belief that the brain mediates all conscious and unconscious experiences- including spiritually experiences -healing, like addictions, can be related to the processes by which the human brain is organized for controlling pleasure and pain. Here we hypothesize that a healthy spirituality may come more naturally to some individuals because of the unique interaction of their genes and their environments, and we review the evidence in support of this view.
Reward Deficiency Syndrome (RDS); Genes; Dopaminergic; Reward dependence; Spirituality; Addiction recovery; Twelve steps
The nucleus accumbens, a site within the ventral striatum, plays a prominent role in mediating the reinforcing effects of drugs of abuse, food, sex, and other addictions. Indeed, it is generally believed that this structure mandates motivated behaviors such as eating, drinking, and sexual activity, which are elicited by natural rewards and other strong incentive stimuli. This article focuses on sex addiction, but we hypothesize that there is a common underlying mechanism of action for the powerful effects that all addictions have on human motivation. That is, biological drives may have common molecular genetic antecedents, which if impaired, lead to aberrant behaviors. Based on abundant scientific support, we further hypothesize that dopaminergic genes, and possibly other candidate neurotransmitter-related gene polymorphisms, affect both hedonic and anhedonic behavioral outcomes. Genotyping studies already have linked gene polymorphic associations with alcohol and drug addictions and obesity, and we anticipate that future genotyping studies of sex addicts will provide evidence for polymorphic associations with specific clustering of sexual typologies based on clinical instrument assessments. We recommend that scientists and clinicians embark on research coupling the use of neuroimaging tools with dopaminergic agonistic agents to target specific gene polymorphisms systematically for normalizing hyper- or hypo-sexual behaviors.
dopamine; mesolimbic systems; neurogenetics; reward deficiency syndrome (RDS); sexual addiction