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Impaired "Set Shifting" in Anorexia Nervosa: An Endophenotype?

Both patients and their healthy sisters had poorer set shifting and perceptual flexibility than controls, and patients performed worse on several other neuropsychological measures.

Because the overt phenotypic behaviors of people with psychiatric disorders are far removed from the specific genetic differences that confer vulnerability, researchers have increasingly focused on the search for "endophenotypes" (i.e., quantifiable disease-associated traits with simple relationships to the underlying genes). In some psychiatric disorders, differences in neuropsychological functioning may represent endophenotypes. These researchers compared 47 pairs of sisters discordant for anorexia nervosa with 47 matched normal controls on neuropsychological tests of "set shifting" (i.e., the ability to move back and forth between tasks, operations, or mental sets, which is a function primarily linked to the prefrontal cortex).

Results were adjusted for obsessive-compulsive, depressive, and anxiety symptoms. To distinguish state from trait features, researchers also compared acutely ill and recovered subjects. On set-shifting and perceptual-flexibility tasks, the patient group and the healthy-sister group performed similarly, but both did significantly worse than the normal control group. In contrast, the three groups were equivalent in verbal fluency and several nonshifting tasks, and patients performed worse than their sisters and normal controls on several other neuropsychological measures. The recovered-patient subgroup did not differ from the acutely ill subgroup on set-shifting tasks.

Comment: These findings suggest that difficulties with set shifting may comprise an endophenotype for anorexia nervosa. Increased rates of reduced cognitive and perceptual flexibility in women are consistent with elevated levels of persistence, perfectionism, and other obsessive-compulsive features found in this population. Such features have been linked to abnormalities in the serotonergic system, which has been implicated in the regulation of certain types of impulsivity and cognitive inflexibility associated with anorexia nervosa.

— Joel Yager, MD

Published in Journal Watch Psychiatry January 12, 2006

Citation(s):

Holliday J et al. Is impaired set-shifting an endophenotype of anorexia nervosa? Am J Psychiatry 2005 Dec; 162:2269-75.

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