Increased Dopamine D2/D3 Receptor Binding After Recovery from Anorexia Nervosa Measured by Positron Emission Tomography and [11C]Raclopride

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Biological Psychiatry (Impact Factor: 10.26). 01/2006; 58(11):908-12. DOI: 10.1016/j.biopsych.2005.05.003
Source: PubMed


Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN).
To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [(11)C]raclopride was used to assess DA D2/D3 receptor binding.
The women who were recovered from AN had significantly higher [(11)C]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [(11)C]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen.
These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and might contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behavior and their ascetic, anhedonic temperament.

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Available from: Walter H Kaye
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    • "These studies revealed a predominant imbalance between the reward and inhibition systems of the brain, which are hallmark characteristics of the disorder. Recovered AN patients show increased dopamine receptor availability ( Frank et al., 2005 ) and also functional magnetic resonance imaging (fMRI) studies point to dopamine dysfunction by discovering hypoactivity of striatal regions in response to pleasurable stimuli ( Kaye et al., 2009 ). This resulted in the notion that AN patients suffer from general anhedonia unable to experience pleasure. "
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    ABSTRACT: Neuroimaging studies investigating the neural profile of anorexia nervosa (AN) have revealed a predominant imbalance between the reward and inhibition systems of the brain, which are also hallmark characteristics of the disorder. However, little is known whether these changes can also be determined independent of task condition, using resting-state functional magnetic resonance imaging, in currently ill AN patients. Therefore the aim of our study was to investigate resting-state connectivity in AN patients (n = 12) compared to healthy athlete (n = 12) and non-athlete (n = 14) controls. For this purpose, we used degree centrality to investigate functional connectivity of the whole-brain network and then Granger causality to analyze effective connectivity (EC), to understand directional aspects of potential alterations. We were able to show that the bilateral inferior frontal gyrus (IFG) is a region of special functional importance within the whole-brain network, in AN patients, revealing reduced functional connectivity compared to both healthy control groups. Furthermore, we found decreased EC from the right IFG to the midcingulum and increased EC from the bilateral orbitofrontal gyrus to the right IFG. For the left IFG, we only observed increased EC from the bilateral insula to the left IFG. These results suggest that AN patients have reduced connectivity within the cognitive control system of the brain and increased connectivity within regions important for salience processing. Due to its fundamental role in inhibitory behavior, including motor response, altered integrity of the inferior frontal cortex could contribute to hyperactivity in AN.
    Full-text · Article · Apr 2014 · Clinical neuroimaging
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    • "Clinically, pure restrictor-type AN individuals are often over-controlled, over-concerned about consequences, and perfectionistic [9]–[12]. They also tend to be anhedonic and ascetic, able to sustain self-denial of food as well as most comforts and pleasures in life [13]. Although the understanding of the pathophysiology of AN and other eating disorders has lagged behind other major psychiatric disorders, a growing body of evidence suggests that AN is a neurobiologically based disorder characterized by alterations in neurocircuitry supporting inhibition and cognitive control [9], [14]–[21]. "
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    ABSTRACT: Individuals with anorexia nervosa (AN) are often cognitively rigid and behaviorally over-controlled. We previously showed that adult females recovered from AN relative to healthy comparison females had less prefrontal activation during an inhibition task, which suggested a functional brain correlate of altered inhibitory processing in individuals recovered from AN. However, the degree to which these functional brain alterations are related to disease state and whether error processing is altered in AN individuals is unknown. In the current study, ill adolescent AN females (n = 11) and matched healthy comparison adolescents (CA) with no history of an eating disorder (n = 12) performed a validated stop signal task (SST) during functional magnetic resonance imaging (fMRI) to explore differences in error and inhibitory processing. The groups did not differ on sociodemographic variables or on SST performance. During inhibitory processing, a significant group x difficulty (hard, easy) interaction was detected in the right dorsal anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left posterior cingulate cortex (PCC), which was characterized by less activation in AN compared to CA participants during hard trials. During error processing, a significant group x accuracy (successful inhibit, failed inhibit) interaction in bilateral MFG and right PCC was observed, which was characterized by less activation in AN compared to CA participants during error (i.e., failed inhibit) trials. Consistent with our prior findings in recovered AN, ill AN adolescents, relative to CA, showed less inhibition-related activation within the dorsal ACC, MFG and PCC as inhibitory demand increased. In addition, ill AN adolescents, relative to CA, also showed reduced activation to errors in the bilateral MFG and left PCC. These findings suggest that altered prefrontal and cingulate activation during inhibitory and error processing may represent a behavioral characteristic in AN that is independent of the state of recovery.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "ol participants , recov - ered AN adults showed excessive activation of the caudate , regardless of trial type , and abnormal activation of the ventral striatum during negative feedback on a guessing game . Together with PET evidence indicating increased D2 / D3 receptor bind - ing in the ventral striatum in both ill and recovered adults with AN ( Frank et al . , 2005 ) , these findings suggest that impaired reward processing within the ventral striatum may contribute to the diminished motivation to eat , as food may not be as rewarding to these individuals as it is to others . Although inter - esting , these data do not inform us about habit learning capabilities within the dorsolateral striatum in "
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