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New insights into symptoms and neurocircuit function of Anorexia Nervosa

Eating Disorder Treatment & Research Program, Department of Psychiatry, University of California, San Diego, La Jolla Village Professional Center, 8950 Villa La Jolla Drive, Suite C-207, La Jolla, California 92037, USA.
Nature Reviews Neuroscience (Impact Factor: 31.38). 09/2009; 10(8):573-84. DOI: 10.1038/nrn2682
Source: PubMed

ABSTRACT Individuals with anorexia nervosa have a relentless preoccupation with dieting and weight loss that results in severe emaciation and sometimes death. It is controversial whether such symptoms are secondary to psychosocial influences, are a consequence of obsessions and anxiety or reflect a primary disturbance of brain appetitive circuits. New brain imaging technology provides insights into ventral and dorsal neural circuit dysfunction - perhaps related to altered serotonin and dopamine metabolism - that contributes to the puzzling symptoms found in people with eating disorders. For example, altered insula activity could explain interoceptive dysfunction, and altered striatal activity might shed light on altered reward modulation in people with anorexia nervosa.

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Available from: Walter H Kaye, Aug 14, 2015
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    • "In addition to craving, the ACC is thought to be involved in conflict monitoring and has been demonstrated to contribute to networks activated during affect regulation, alongside the insula, orbitofrontal cortex and lateral prefrontal regions (Veit et al., 2012). Dysfunction in the anterior insula is proposed to contribute to altered interoceptive awareness (Kaye et al., 2009). Regulation of the amygdala, a primary emotion processing centre (Zotev et al., 2011), the anterior insula (Veit et al., 2012) and specific regions of the lateral prefrontal cortex (McCaig et al., 2011) have been successfully accomplished using rt-fMRI neurofeedback in healthy individuals, with reports of clinical benefit associated with successful regulation in patient groups (e.g. "
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    • "Mounting evidence supports disruption of food motivation and reward circuitry functioning in women with anorexia nervosa (AN) (Ellison et al., 1998; Uher et al., 2003, 2004; Santel et al., 2006; Wagner et al., 2007, 2008; Kaye et al., 2009; Fladung et al., 2010; Gizewski et al., 2010; Cowdrey et al., 2011; Joos et al., 2011; Frank et al., 2012; Holsen et al., 2012). Functional neuroimaging studies that directly compare active and recovered patients with healthyweight controls offer insight into state vs. potential " trait " features of the neural signature of AN (Uher et al., 2003; Holsen et al., 2012). "
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    ABSTRACT: Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies.
    Psychiatry Research : Neuroimaging 05/2014; 223(2). DOI:10.1016/j.pscychresns.2014.04.015 · 2.83 Impact Factor
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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.
    04/2014; 4:615–622. DOI:10.1016/j.nicl.2014.04.002
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