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      The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa

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          Abstract

          This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN.

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          Most cited references42

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          'Liking' and 'wanting' food rewards: brain substrates and roles in eating disorders.

          What brain reward systems mediate motivational 'wanting' and hedonic 'liking' for food rewards? And what roles do those systems play in eating disorders? This article surveys recent findings regarding brain mechanisms of hedonic 'liking', such as the existence of cubic-millimeter hedonic hotspots in nucleus accumbens and ventral pallidum for opioid amplification of sensory pleasure. It also considers brain 'wanting' or incentive salience systems important to appetite, such as mesolimbic dopamine systems and opioid motivation circuits that extend beyond the hedonic hotspots. Finally, it considers some potential ways in which 'wanting' and 'liking' might relate to eating disorders.
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            Relapse in anorexia nervosa: a survival analysis.

            Knowledge about factors that predict relapse in anorexia nervosa (AN) is needed for the development of effective relapse prevention treatments and may also advance understanding of the psychopathology of AN. The aim of the present study was to examine the rate, timing and prediction of relapse in AN following weight restoration in a specialized in-patient treatment programme. Fifty-one consecutive first-admission AN patients who were weight-restored following in-patient treatment participated in the study. Follow-up assessments were conducted a median of 15 months post-discharge. Relapse of AN was defined as a body mass index <17.5 for 3 consecutive months. Data were analysed using Kaplan-Meier survival analysis and Cox regression. The overall rate of relapse was 35% and the mean survival time was 18 months. The highest risk period was from 6 to 17 months after discharge. Several significant predictors of relapse were identified: a history of suicide attempt; previous specialized treatment for an eating disorder; severity of obsessive-compulsive symptoms at presentation; excessive exercise immediately after discharge; and residual concern about shape and weight at discharge. There continues to be a significant risk of relapse among AN patients who remain well for the first year post-discharge. Several variables were shown to be associated with an elevated risk of relapse. These findings have implications for the development of initial treatments and relapse prevention strategies for AN.
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              Altered reward processing in women recovered from anorexia nervosa.

              Individuals with anorexia nervosa are known to be ascetic and able to sustain self-denial of food as well as most comforts and pleasures in life. Building on previous findings of altered striatal dopamine binding in anorexia nervosa, the authors sought to assess the response of the anterior ventral striatum to reward and loss in this disorder. Striatal responses to a simple monetary reward task were investigated using event-related functional magnetic resonance imaging. To avoid the confounding effects of malnutrition, the authors compared 13 healthy comparison women and 13 women who had recovered from restricting-type anorexia nervosa and had 1 year of normal weight and regular menstrual cycles, without binge eating or purging. Recovered women showed greater hemodynamic activation in the caudate than comparison women. Only the recovered women showed a significant positive relationship between trait anxiety and the percentage change in hemodynamic signal in the caudate during either wins or losses. In contrast, in the anterior ventral striatum, comparison women distinguished positive and negative feedback, whereas recovered women had similar responses to both conditions. Individuals who have recovered from anorexia nervosa may have difficulties in differentiating positive and negative feedback. The exaggerated activation of the caudate, a region involved in linking action to outcome, may constitute an attempt at "strategic" (as opposed to hedonic) means of responding to reward stimuli. The authors hypothesize that individuals with anorexia nervosa have an imbalance in information processing, with impaired ability to identify the emotional significance of a stimulus but increased traffic in neurocircuits concerned with planning and consequences.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 January 2016
                2016
                : 11
                : 1
                : e0145894
                Affiliations
                [1 ]King’s College London, Institute of Psychiatry, Psychology & Neuroscience, Department of Psychological Medicine, Section of Eating Disorders, London, United Kingdom
                [2 ]Department of Psychiatry, McGill University, Montreal, QC, Canada
                Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CBO ML ICC US. Performed the experiments: CBO AK BR. Analyzed the data: CBO. Contributed reagents/materials/analysis tools: CBO AK BR ML ICC US. Wrote the paper: CBO ML ICC US.

                Article
                PONE-D-15-46894
                10.1371/journal.pone.0145894
                4726788
                26808920
                c26d4f82-fbc9-4473-8195-ae2081ee2b3d
                © 2016 O’Hara et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 October 2015
                : 9 December 2015
                Page count
                Figures: 1, Tables: 3, Pages: 16
                Funding
                This study was supported by the Swiss Anorexia Foundation (project number 10-11) and by the NIHR Biomedical Research Centre (BRC) for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London (grant number 12421). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Iain Campbell and Ulrike Schmidt receive salary support from the BRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Eating Disorders
                Anorexia Nervosa
                Medicine and Health Sciences
                Public and Occupational Health
                Physical Fitness
                Exercise
                Medicine and Health Sciences
                Sports and Exercise Medicine
                Exercise
                Biology and Life Sciences
                Sports Science
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                Exercise
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Amines
                Catecholamines
                Dopamine
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