Serotonin Activity Weight-Restored Anorexics - Brief Article

Nutrition Research Newsletter, August, 2001 by Guido K. Frank, Walter H. Kaye, Thedore E. Weltzin

Patients with anorexia nervosa (AN) have disturbances of appetite and behaviors, such as dysphoria, inhibition and obsessional thinking, that could be related to altered serotonin activity. Some studies have even claimed that alterations of the serotonin neurotransmitter system may contribute to the pathophysiology of AN, with altered brain serotonin activity playing a role in increased satiety and weight loss in anorexic patients.

One tool that can be used to investigate the relationship between brain serotonin activity and different behaviors is meta-chlorophenylpiperazine (m-CPP), a relatively serotonin-specific drug. To investigate these relationships and reduce the confounding effects of malnutrition and low body weight, a group of researchers from the University of Pittsburgh studied a group of subjects who had previously been underweight with AN and who had been restored to a normal body weight at the time of this study.

All 12 subjects included in this study had been hospitalized for treatment of anorexia on the Eating Disorders Unit of Western Psychiatric Institute and clinic at the University of Pittsburgh. Three of the patients were purging anorexics but none binged. The subjects were studied 12 [ or -] 4 days after attaining their target weight (95 [ or -] 2% of their actual body weight) (ABW). Twelve healthy control women (CW) were admitted to the laboratory on the same inpatient unit the night prior to the study. Each of the women ingested 0.5 mg/kg m-CPP or a placebo and blood samples were taken at intervals thereafter. Subjects were given m-CPP and placebo in random order. Ratings of psychological states on the morning before the study and after the administration of m-CPP and placebo were done two ways. First, behavioral states of anxiety, depression, euphoria, body image distortion and obsessive thinking were assessed by two psychiatrists at baseline and after treatment. Second, subjects self-rated their moods at baseline and at 30-minute intervals for 12 hours after receiving m-CPP or placebo.

Short-term recovered anorexics weighed significantly less and were younger than control subjects. There was no difference between plasma m-CPP levels between the two groups. However, the anorexics had significantly reduced prolactin and cortisol levels and a trend toward elevated growth hormone compared with the controls. At baseline, they exhibited distortion and obsessional thoughts. After administration of m-CPP compared with placebo, anorexic subjects had a significantly greater reduction in body image distortion, were less anxious and less depressed.

After short-term weight restoration, anorexic patients had elevations of baseline symptoms of depression, anxiety, and obsessionality with the administration of m-CPP. This occurred on two separate scales (psychiatric rater and self-assessment). A surprising finding was that nine of the 12 anorexic subjects had less preoccupation with feeling fat after the m-CPP. The authors are not sure whether this was secondary to elevated mood or to some direct effect of the m-CPP on obsessions about body image distortion. The mechanism responsible for the elevated mood and/or reduced behavioral inhibition is uncertain. Therefore, more studies should be conducted on the pros/cons of m-CPP administration.

Guido K. Frank, Walter H. Kaye, Theodore E. Weltzin, et al. Altered Response to Meta-Chlorophenylpiperazine in Anorexia Nervosa: Support for a Persistent Alteration of Serotonin Activity After Short-Term Weight Restoration, International Journal of Eating Disorders 30:57-68 (July 2001) [Correspondence to: Walter H. Kaye, University of Pittsburgh, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Room E-724, Pittsburgh, PA 15213. E-mail: kayewh@msx.upmc.edu].