Charting the Brain to Better Define AN

Reprinted from Eating Disorders Review
September/October 2009 Volume 20, Number 5
©2009 Gürze Books

Dr. Walter Kaye and his colleagues at the University of California, San Diego, could be described as modern-day equivalents of Lewis and Clark, with an exception. Their main target for exploration is the brain, and new brain imaging technology is helping them chart portions of the brain that may be responsible for producing the symptoms in anorexia nervosa (AN).

Persons with AN have a relentless preoccupation with dieting and losing weight that leads to severe emaciation and, in at least 6% of patients, to death. Patients often have strikingly similar symptoms: onset in early adolescence, stereotypic presentation of symptoms and course, and most are female. Although AN is characterized as an eating disorder, it is still not known whether there is a primary disturbance of appetite pathways or whether disturbed appetite follows other phenomena, such as anxiety or obsessional preoccupation with weight gain.

Target: Ventral and dorsal circuits

Many have been interested in the role of the hypothalamus in food and weight regulation in patients with AN, although it is not known whether hypothalamic changes are a cause or a consequences of the symptoms. In a recent article, Dr. Kaye and Drs. Julie L. Fudge and Martin Paulus turned instead to another possibility—dysfunction of ventral and dorsal neural circuits in the brain (Nature Reviews/Neuroscience 2009; 10:573).

According to Dr. Kaye and colleagues, common comorbid behaviors typical of both recovered and ill AN persons are often expressed together. These include inhibition, anxiety, depression and obsesionality, and other symptoms that can be puzzling, including body image distortion and anhedonia. Dr. Kaye and his colleagues note that these behaviors could be encoded in limbic and cognitive circuits that modulate and integrate neuronal processes related to appetite, emotionality, and cognitive control.

Two neurocircuits that have been identified from brain imaging, neurophysiologic, and lesion studies might be particularly relevant to behavior in patients with AN. A ventral (limbic) neurocircuit that includes the amygdale, insala, ventral striatum and ventral regions of the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC) seems to be important for identifying the emotional significance of stimuli and for sending an affective response to these stimuli. A dorsal (cognitive) neurocircuit is thought to modulate selective attention, planning, and effortful regulation of affective states and includes the hippocampus, dorsal regions of the ACC, dorsolateral prefrontal cortex, parietal cortex, and other regions.

Dr. Kaye points out that earlier brain imaging studies have shown that subjects who have recovered from AN have altered activity in the frontal, anterior cingulate, and parietal regions. Just as dysregulation of these two circuits contributes to several psychiatric disorders, including major depression, anxiety disorders, and obsessive-compulsive disorders, it is possible that altered brain function of these circuits also alters emotion regulation.

The authors propose that somatic, autonomic, and visceral information is aberrantly processed in people who are vulnerable to developing AN. Then, brain changes associated with puberty might further challenge these processes.

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