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      Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

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          Abstract

          Background and aims

          Many patients presenting multiple behaviors including drug and food abuse as well as other pathological repetitive unwanted activities such as gambling, self-mutilation and paraphilias may not be appropriately diagnosed. Here we present a case of a male presenting many of these seemingly diverse behaviors and finally diagnosed with reward deficiency syndrome (RDS) by his attending physician.

          Methods

          The use of the dopamine agonist, ropinirole after two weeks showed improvement in terms of sexual behavior but tolerance set in and was discontinued especially when an infraction occurred with the patient's insurance. In this article, we carefully explore the potential of ropinirole to downregulate dopamine receptors causing adenylate cyclase receptor supersensitivity and tolerance a feature of neurotransmitter cross-talk. Based on previous scientific evidence showing KB220Znutrigenomic amino-acid therapy (NAAT) to rapidly (post one-hour) activate dopaminergic pathways in both the pre-frontal cortex cingulate gyrus (relapse loci) and ventral tegmental area-caudate-accumbens-putamen (craving and emotion loci) the patient was prescribed NAAT.

          Results and discussion

          Within one week of utilization the repetitive paraphilia was eliminated. There were also a number of other positive effects such as enhanced focus that persisted even after the patient stopped using KB220Z suggesting neuroplasticity (e.g. altruistic thoughts). However, these observed profound benefits require more in-depth study, especially in a large cohort against a placebo. While this report focused on a rapid response rather than long-term benefits previously associated with NAAT, it is somewhat encouraging and longer term required follow-up and larger placebo controlled studies are warranted before any definitive conclusions could be gleaned from this case report.

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          Most cited references31

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          Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary

          Background and hypothesis Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors. Proposal and conclusion The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine™, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system.
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            Rise and fall of anti-obesity drugs.

            Although it is not generally a life-threatening disease, obesity is becoming a major health problem worldwide. It can be controlled by means of drugs, and, consequently, these are required to be safe as well as effective. In this paper, we summarize the fate of various drugs that have been introduced for clinical use in the treatment of obesity. Fenfluramine and dexfenfluramine were withdrawn because of heart valve damage. Sibutramine suppresses appetite and increases heart rate and blood pressure. In the Sibutramine Cardiovascular OUTcomes trial, an increase in major adverse cardiovascular events prompted its withdrawal in Europe and the United States. Rimonabant is an endocannabinoid receptor antagonist that reduces body weight and ameliorates some cardiovascular risk factors. However, adverse psychiatric side effects led to its withdrawal as well. Orlistat is approved in Europe and the United States for the treatment of obesity, but its use is limited by gastrointestinal side-effects. Ephedrine and caffeine are natural ingredients in foods and supplements that may help the person to lose weight. In the light of several failed attempts, there is a clear need to develop drugs that are effective and safe in the long term in order to successfully combat the phenomenon of obesity .
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              Neurochemical regulation of pair bonding in male prairie voles.

              Pair bonding represents social attachment between mates and is common among monogamous animals. The prairie vole (Microtus ochrogaster) is a monogamous rodent in which mating facilitates pair bond formation. In this review, we first discuss how prairie voles have been used as an excellent model for neurobiological studies of pair bonding. We then primarily focus on male prairie voles to summarize recent findings from neuroanatomical, neurochemical, cellular, molecular, and behavioral studies implicating vasopressin (AVP), oxytocin (OT), and dopamine (DA) in the regulation of pair bonding. Possible interactions among these neurochemicals in the regulation of pair bonding, the brain areas important for pair bond formation, and potential sexually dimorphic mechanisms underlying pair bonding are also discussed. As analogous social bonds are formed by humans, investigation of the neurochemical regulation of pair bond formation in prairie voles may be beneficial for our understanding of the mechanisms associated with normal and abnormal social behaviors in humans.
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                Author and article information

                Journal
                2006
                122266
                Journal of Behavioral Addictions
                JBA
                Akadémiai Kiadó, co-published with Springer Science+Business Media B.V., Formerly Kluwer Academic Publishers B.V.
                2062-5871
                2063-5303
                1 June 2013
                : 2
                : 2
                : 117-124
                Affiliations
                [ 1 ] Center for Psychiatric Medicine, North Andover, Massachusetts, USA
                [ 2 ] Department of Psychiatry, Anatomy & Neurobiology, Boston VA and Boston University School of Medicine, Boston, Massachusetts, USA
                [ 3 ] Department of Psychiatry, Global Integrated Services Unit of Vermont Center for Clinical & Translational Science, University of Vermont College of Medicine, Burlington, Vermont, USA
                [ 4 ] Department of Holistic Medicine, G & G Health Care Services LLC, North Miami Beach, Florida, USA
                [ 5 ] Center for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal, India
                [ 6 ] Department of Nutrigenomics, LifeGen, Inc., Austin, Texas, USA
                [ 7 ] Department of Psychiatry and McKnight Brain Institute, University of Florida, College of Medicine, Gainesville, Florida, USA
                [ 8 ] Department of Clinical Neurology, PATH Foundation NY, New York, New York, USA
                [ 9 ] Department of Management Science and Statistics, the University of Texas at San Antonio, San Antonio, Texas, USA
                [ 10 ] Dominion Diagnostics, LLC, North Kingstown, Rhode Island, USA
                [ 11 ] Department of Addiction Research & Therapy, Malibu Beach Recovery Center, Malibu Beach, California, USA
                [ 12 ] Department of Psychiatry, College of Medicine, University of Florida, and McKnight Brain Institute, Gainesville, Florida, USA
                Author notes
                Article
                8
                10.1556/jba.2.2013.2.8
                26165932
                94c64e26-b503-4e28-ba09-9c3478071537
                © 2013 The Author(s)

                Open Access statement. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.

                History
                : 18 March 2013
                : 2 May 2013
                : 3 May 2013
                Categories
                Case Report

                Medicine,Psychology,Social & Behavioral Sciences,Clinical Psychology & Psychiatry
                reward deficiency syndrome (RDS),Tourette's,aggressive sexual behavior,NAAT,repetitive paraphilia behavior,dopamine activation

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