A Neural Signature of Anorexia Nervosa in the Ventral Striatal Reward System

University of Ulm, Department of Psychiatry, Leimgrubenweg 12-14, 89075 Ulm, Germany.
American Journal of Psychiatry (Impact Factor: 12.3). 10/2009; 167(2):206-12. DOI: 10.1176/appi.ajp.2009.09010071
Source: PubMed


Animal studies assessing mechanisms of self-starvation under conditions of stress and diet suggest a pivotal role for the mesolimbic reward system in the maintenance of core symptoms in anorexia nervosa, which is corroborated by initial empirical evidence in human studies. The authors examined activity in the ventral striatal system in response to disease-specific stimuli in women with acute anorexia nervosa.
Participants were 14 women with acute anorexia nervosa and 14 matched healthy comparison women who underwent functional magnetic resonance imaging (fMRI) during evaluation of visual stimuli depicting a female body with underweight, normal weight, and overweight canonical whole-body features according to standardized body mass indices. Participants were required to process each stimulus in a self-referring way. Ratings for each weight category were used as the control task.
Behaviorally, women with anorexia nervosa provided significantly higher positive ratings in response to underweight stimuli than in response to normal-weight stimuli, while healthy comparison women showed greater preference for normal-weight stimuli relative to underweight stimuli. Functionally, ventral striatal activity demonstrated a highly significant group-by-stimulus interaction for underweight and normal-weight stimuli. In women with anorexia nervosa, activation was higher during processing of underweight stimuli compared with normal-weight stimuli. The reverse pattern was observed in healthy comparison women.
These findings are consistent with predictions in animal studies of the pivotal role of the human reward system in anorexia nervosa and thus support theories of starvation dependence in maintenance of the disorder.

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Available from: Georg Grön, Sep 10, 2015
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    • "Neuroimaging has indicated that people recovered from AN lack differential activation in reward-related neurocircuitry in response to monetary wins and losses[9]. Moreover, fMRI investigations indicate that individuals with AN show increased responses to AN-related cues (underweight body[10]and taste- reward[11,12]stimuli) in the ventral striatum, a DA-innervated brain region implicated in reward. These studies associating DA function with AN are supported by animal studies which show that chronic food restriction sensitises the mesolimbic DA system[13]. "
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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.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "Mesolimbic dopamine neurons are thought to be involved with reward (Wise, 2004), and Bergh and Södersten (1996) suggested that dieting, along with high levels of exercise, can lead to a stress response (Hotta et al., 1986; Rojo et al., 2006) that increases cortisol and corticotrophin releasing factor (Estour et al., 2010; Gwirtsman et al., 1989; Schorr et al., 2015; Shibuya et al., 2011). Stress then increases dopamine levels through these mechanisms (Holly et al., 2015; Wanat et al., 2008) and the nucleus accumbens, i.e., a region of the dopamine terminals in the ventral striatum, is in fact activated in anorexics (Fladung et al., 2010, 2013; Foerde et al., 2015; Frank, 2014; Keating et al., 2012; O'Hara et al., 2015; Wierenga et al., 2014, 2015). The elevated dopamine response is then thought to assist the sequence from rewarding behaviors such as dieting and exercise to become habits not unlike drug dependency or self-starvation by conditioning of this kind of reward to initially neutral stimuli (Bergh and Södersten, 1996; Everitt and Robbins, 2005; Jansen, 1998; Méquinion et al., 2015; Södersten et al., 2008). "
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    ABSTRACT: SÖDERSTEN, P., C. Bergh, M. Leon and M. Zandian. Dopamine and Anorexia Nervosa. NEUROSCI BIOBEHAV REV ab(c) XXX-XXX, 2015. - We have suggested that reduced food intake increases the risk for anorexia nervosa by engaging mesolimbic dopamine neurons, thereby initially rewarding dieting. Recent fMRI studies have confirmed that dopamine neurons are activated in anorexia nervosa, but it is not clear whether this response is due to the disorder or to its resulting nutritional deficit. When the body senses the shortage of nutrients, it rapidly shifts behavior toward foraging for food as a normal physiological response and the mesolimbic dopamine neurons may be involved in that process. On the other hand, the altered dopamine status of anorexics has been suggested to result from a brain abnormality that underlies their complex emotional disorder. We suggest that the outcomes of the treatments that emerge from that perspective remain poor because they target the mental symptoms that are actually the consequences of the food deprivation that accompanies anorexia. On the other hand, a method that normalizes the disordered eating behavior of anorexics results in much better physiological, behavioral and emotional outcomes.
    Full-text · Article · Nov 2015 · Neuroscience & Biobehavioral Reviews
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    • "ed activation of brain dopamine reward circuits in response to food stimuli ( Frank et al . , 2012 ) . Similarly , women with anorexia also demonstrate increased ventral striatal reward responsiveness , the same region of the brain that has been found to activate in response to consumption of addictive substances , to images of underweight women ( Fladung et al . , 2010 ) . Thus , increasing evidence that dysregulated positive emotion is involved in anorexia only emphasizes the need for research to further clarify this association ."
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    ABSTRACT: Growing evidence indicates that both positive and negative emotion potentially influence the development and maintenance of anorexia nervosa, through both positive and negative reinforcement of weight loss activities. Such reactive emotional experience may be characterized by frequent and intense fluctuations in emotion, a construct known as "emotional instability." The purpose of this study was to investigate the association between positive emotional instability and weight loss activities in anorexia nervosa, and to investigate the synergistic effects of positive and negative emotional instability on promoting weight loss activities. Using ecological momentary assessment methods, 118 participants with anorexia nervosa reported their emotional experiences and behaviors at least six times daily over 2 weeks using a portable digital device. Using generalized linear modeling, results indicated that high levels of both positive and negative emotional instability, and the interaction between the two, were associated with more frequent weight-loss activities, beyond anorexia subtype and mean levels of emotional intensity. These findings indicate that when women with anorexia exhibit both high levels of both positive and negative emotional instability they are more prone to a variety of weight loss activities. The importance of addressing the role of both positive and negative emotion in anorexia treatment is discussed.
    Full-text · Article · Sep 2015 · Frontiers in Psychology
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