New insights into symptoms and neurocircuit function of anorexia nervosa

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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.

Key Points

  • Individuals with anorexia nervosa (AN) exhibit an ego-syntonic resistance to eating and a powerful pursuit of weight loss, yet are paradoxically preoccupied with food and eating rituals to the point of obsession. Moreover, these individuals have a distorted body image and, even when emaciated, tend to see themselves as 'fat', express denial of being underweight and compulsively over-exercise.

  • Premorbid, childhood personality and temperament traits, which are thought to be genetically-determined, are thought to contribute to a vulnerability to develop AN. These include negative emotionality, harm avoidance, perfectionism, inhibition, a drive for thinness, altered interoceptive awareness and obsessive-compulsive personality traits.

  • Individuals with AN seem to have a paradoxical response to eating; they engage in dietary restraint in order to reduce anxiety, because eating stimulates dysphoric mood. Several lines of evidence raise the possibility that altered serotonin (5-HT) function contributes to anxiety in subjects with AN, and starvation is a means of diminishing 5-HT functional activity.

  • Individuals with AN might have a trait towards an imbalance between serotonin and dopamine pathways, which may have a role in an altered interaction between ventral (limbic) neurocircuits, which are important for identifying the emotional significance of stimuli and for generating an affective response to these stimuli, and dorsal (cognitive) neurocircuits that modulate selective attention, planning and effortful regulation of affective states.

  • Recent functional MRI studies support the possibility that individuals with AN might be less able to precisely modulate affective responses to immediately salient stimuli but have increased activity in neurocircuits concerned with planning and consequences.

  • Coding the awareness of pleasant sensation from the taste experience through the anterior insula might be altered in individuals with AN, tipping the balance of striatal processes away from normal, automatic reward responses mediated by the ventral striatum and towards a more 'strategic' approach mediated by the dorsal striatum.

  • Perfectionism and obsessional personality traits could be related to exaggerated cognitive control by the dorsal lateral prefrontal cortex (which may have excessive inhibitory activity and thus dampen information processing through reward pathways) or to compensation for primary deficits in limbic function. When there are deficits in emotional regulation, overdependence upon cognitive rules is a reasonable strategy of self-management.

  • The temperament and personality traits that create a vulnerability to develop AN also persist after recovery. After recovery, these traits tend to have positive aspects, including attention to detail, concern about consequences and a drive to accomplish and succeed.

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Figure 1: The time course and phenomenology of anorexia nervosa.
Figure 2: The role of serotonin neural function in anorexia nervosa.
Figure 3: Cortical-striatal pathways with a focus on taste.
Figure 4: Impaired balance between interoceptive and reward processing.


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Much of the research incorporated into this Review was supported for W.H.K. by the National Institute of Mental Health (NIMH) (046001, 042984, 066122 and 001894) and the Price Foundation, for J.L.F. by the NIMH (063291) and for M.P. by the National Institute on Drug Abuse (016663, 018307 and 020687) and the Center of Excellence in Stress and Mental Health.

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Correspondence to Walter H. Kaye.

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The sensing and integrating of afferent proprioceptive and visceroceptive information, resulting in feeling the 'inner state' of the body, which is important for allocating attention, evaluating context and planning actions.


A sensation related to or characterized by pleasure


A sensation originating from the internal organs.


A sensation originating from the joints and the subcutaneous tissues.

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