The Effects of Tryptophan Depletion

Dieting may promote relapse among women who have recovered from depression, due to depletion of the serotonin precursor tryptophan, according to the results of a recent British study (Br J Psychiatry 2000;176:72). And, a second study has shown that persons with bulimia nervosa (BN) may turn to dieting and binge eating to regulate their unstable serotonin system after tryptophan depletion (Biol Psychiatry 2000;47:151).

Women who have recovered from depression have an abnormal sensitivity to the mood-lowering effects of acute tryptophan depletion induced by a tryptophan-free amino acid mixture. This suggests that they may have abnormalities in the regulation of brain serotonin (5-HT) function.

In some, a failure to regulate 5-HT function

In the first study, women with a history of depression showed impaired regulation of 5-HT function in response to dieting. Katharine A. Smith, MRCPsych, and co-workers placed women with and without a history of major depression on a 1000 kcal/day diet for 3 weeks. Just before the study began and during the final week of the diet, the researchers measured fasting plasma tryptophan levels and the prolactin response to an intravenous tryptophan challenge in all women.

Of the 43 women who entered the study, 25 completed the protocol (14 controls, 11 recovered patients). Although plasma tryptophan levels fell by about 10% in both groups after the diet, the prolactin response to tryptophan increased after dieting only among the women in the control group.

The pre-diet response to the tryptophan challenge was similar in both groups. The results suggest that if there is a trait abnormality in women vulnerable to major depression, it may be apparent only when 5-HT function comes under biochemical stress. Although there was only a minimal difference in the mood effects of dieting between the 2 groups, the more marked neuroendocrine differences among the depressed patients suggest that vulnerability to a relapse to depression may be related to an inability to upregulate brain 5-HT function in response to stress.

5-HT and the pathogenesis of BN

In a second study, Walter H. Kaye, MD and colleagues found that women with bulimia nervosa (BN) seem more vulnerable than normal controls to the effects of acute tryptophan depletion (Biol Psychiatry 2000;47:151). Numerous studies suggest that a disturbance of 5-HT neuronal function may be trait-related and may contribute to the pathogenesis of BN.

Twenty-two women with BN and 16 healthy controls were studied on 2 separate days during the follicular stage of the menstrual cycle. The participants drank a mixture of essential amino acids and tryptophan on one day and a tryptophan-deficient mixture on the second day, in a double-blind design. Mood/appetite rating were recorded and blood samples were taken at baseline and at hourly intervals of up to 7 hours. The participants were then offered a variety of foods and were allowed to binge and vomit if they wished.

After acute tryptophan depletion, women with bulimia nervosa had a significantly greater increase in peak depression, mood lability, sadness and desire to binge compared to the control group.

Dr. Kaye and colleagues hypothesize that the 5-HT neuronal system is poorly modulated and inherently unstable in persons with BN. Thus, the 5-HT system fluctuates erratically among BN patients, rather than precisely compensating and buffering the effects of diet or stress, as it does in normal women. Because of this, persons with BN may use dieting and binge eating to adjust their unstable 5-HT system.

Conceivably, the findings in depression and those in BN may show some common history and features. Studies in patients recovered from BN with and without past histories of depressive disorders may help clarify the picture.