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      Hatching the behavioral addiction egg: Reward Deficiency Solution System (RDSS)™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric

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          Abstract

          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.

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          Most cited references196

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          Relation of reward from food intake and anticipated food intake to obesity: a functional magnetic resonance imaging study.

          The authors tested the hypothesis that obese individuals experience greater reward from food consumption (consummatory food reward) and anticipated consumption (anticipatory food reward) than lean individuals using functional magnetic resonance imaging (fMRI) with 33 adolescent girls (mean age = 15.7, SD = 0.9). Obese relative to lean adolescent girls showed greater activation bilaterally in the gustatory cortex (anterior and mid insula, frontal operculum) and in somatosensory regions (parietal operculum and Rolandic operculum) in response to anticipated intake of chocolate milkshake (vs. a tasteless solution) and to actual consumption of milkshake (vs. a tasteless solution); these brain regions encode the sensory and hedonic aspects of food. However, obese relative to lean adolescent girls also showed decreased activation in the caudate nucleus in response to consumption of milkshake versus a tasteless solution, potentially because they have reduced dopamine receptor availability. Results suggest that individuals who show greater activation in the gustatory cortex and somatosensory regions in response to anticipation and consumption of food, but who show weaker activation in the striatum during food intake, may be at risk for overeating and consequent weight gain. (PsycINFO Database Record (c) 2008 APA, all rights reserved).
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            Measuring Adiposity in Patients: The Utility of Body Mass Index (BMI), Percent Body Fat, and Leptin

            Background Obesity is a serious disease that is associated with an increased risk of diabetes, hypertension, heart disease, stroke, and cancer, among other diseases. The United States Centers for Disease Control and Prevention (CDC) estimates a 20% obesity rate in the 50 states, with 12 states having rates of over 30%. Currently, the body mass index (BMI) is most commonly used to determine adiposity. However, BMI presents as an inaccurate obesity classification method that underestimates the epidemic and contributes to failed treatment. In this study, we examine the effectiveness of precise biomarkers and duel-energy x-ray absorptiometry (DXA) to help diagnose and treat obesity. Methodology/Principal Findings A cross-sectional study of adults with BMI, DXA, fasting leptin and insulin results were measured from 1998–2009. Of the participants, 63% were females, 37% were males, 75% white, with a mean age = 51.4 (SD = 14.2). Mean BMI was 27.3 (SD = 5.9) and mean percent body fat was 31.3% (SD = 9.3). BMI characterized 26% of the subjects as obese, while DXA indicated that 64% of them were obese. 39% of the subjects were classified as non-obese by BMI, but were found to be obese by DXA. BMI misclassified 25% men and 48% women. Meanwhile, a strong relationship was demonstrated between increased leptin and increased body fat. Conclusions/Significance Our results demonstrate the prevalence of false-negative BMIs, increased misclassifications in women of advancing age, and the reliability of gender-specific revised BMI cutoffs. BMI underestimates obesity prevalence, especially in women with high leptin levels (>30 ng/mL). Clinicians can use leptin-revised levels to enhance the accuracy of BMI estimates of percentage body fat when DXA is unavailable.
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              Weight gain is associated with reduced striatal response to palatable food.

              Consistent with the theory that individuals with hypofunctioning reward circuitry overeat to compensate for a reward deficit, obese versus lean humans have fewer striatal D2 receptors and show less striatal response to palatable food intake. Low striatal response to food intake predicts future weight gain in those at genetic risk for reduced signaling of dopamine-based reward circuitry. Yet animal studies indicate that intake of palatable food results in downregulation of D2 receptors, reduced D2 sensitivity, and decreased reward sensitivity, implying that overeating may contribute to reduced striatal responsivity. Thus, we tested whether overeating leads to reduced striatal responsivity to palatable food intake in humans using repeated-measures functional magnetic resonance imaging. Results indicated that women who gained weight over a 6 month period showed a reduction in striatal response to palatable food consumption relative to weight-stable women. Collectively, results suggest that low sensitivity of reward circuitry increases risk for overeating and that this overeating may further attenuate responsivity of reward circuitry in a feedforward process.
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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 September 2014
                26 August 2014
                : 3
                : 3
                : 149-156
                Affiliations
                [ 1 ] Department of Psychiatry and McKnight Brain Institute, University of Florida, College of Medicine, PO Box 103424, Gainesville, Florida, 32610-3424, USA
                [ 2 ] Center for Psychiatric Medicine, North Andover, MA, USA
                [ 3 ] Department of Clinical Medicine, Malibu Beach Recovery Center, Malibu Beach, CA, USA
                [ 4 ] Department of Clinical Neurology, PATH Foundation NY, New York, NY, USA
                [ 5 ] Community Mental Health Institute, Human Global Center for Clinical & Translational Science, University of Vermont, Burlington, VT, USA
                [ 10 ] Department of Psychiatry, University of Vermont, College of Medicine, Burlington, VT, USA
                [ 6 ] Dominion Diagnostics, Inc., North Kingstown, RI, USA
                [ 7 ] Department of Personalized Medicine, IGENE, LLC, Austin, TX, USA
                [ 8 ] University of Stellenbosch, Cape Town, South Africa
                [ 9 ] Department of Management Science and Statistics, University of Texas at San Antonio, San Antonio, Texas, USA
                Author notes
                [* ] +1-619-890-2167, +1-352-392-9887, drd2gene@ 123456gmail.com
                Article
                2
                10.1556/jba.3.2014.019
                57044bf4-2d24-44ed-84b9-87eeb795aa58
                © 2014 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
                : 28 May 2014
                : 4 July 2014
                : 4 July 2014
                Categories
                Review Article

                Medicine,Psychology,Social & Behavioral Sciences,Clinical Psychology & Psychiatry
                epigenetics,dopaminergic,neurogenetics,dopamine agonist therapy,Reward Deficiency Syndrome

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