Serotonin and the eating disorders : the effects of dieting, acute plasma tryptophan depletion and mCPP administration on brain 5-HT function

Abstract

The past two decades have seen an upturn in interest in the psychiatric disorders anorexia and bulimia nervosa. Although this renewed interest has been reflected in the amount of research being undertaken, little is understood about the aetiology of these often devastating disorders. In particular, only limited work has been carried out examining the possible neurobiological abnormalities that may underlie, or impart vulnerability to the development of anorexia and bulimia nervosa. While evidence now exists to suggest that serotonergic dysregulation occurs during clinical episodes of both disorders, the precise nature of the dysregulation remains unclear. Furthermore, interpretation of eating disorder research is complicated by confounding factors of the illnesses themselves, including weight loss and the physical consequences of behaviours such as bingeing and purging, and by a paucity of knowledge regarding the normal control of human feeding behaviour. The work in this thesis uses three experimental paradigms, i.e. the neuroendocrine challenge test, a test meal procedure and administration of an amino acid drink free in tryptophan, to examine the role of serotonin in the development of the eating disorders. More specifically, the neuroendocrine approach was used to examine the effects of weight loss on d-fenfluramine and meta chlorophenylpiperazine-induced prolactin responses in healthy controls and, in combination with a test meal, to examine the effects of mchlorophenylpiperazine on food intake and prolactin response in healthy women. In addition, the effect of a tryptophan-free amino acid drink on mood and food intake was examined in both healthy women and in women recovered from bulimia nervosa. Experimental findings reported in this thesis demonstrate no effect of tryptophan-free amino acid drink administration on mood and food intake. In contrast, evidence is presented in support of the hypothesis that moderate dieting is associated with alterations in brain serotonin function, and that such effects are confined to women, suggesting that women are more vulnerable than men to the effects of weight loss and altered food intake. The mechanism underlying dieting-induced alterations in brain serotonin function is discussed, with experimental evidence suggesting a possible pre-synaptic site of action. Studies utilising the serotonin agonist meta-chlorophenylpiperazine confirm the importance of serotonergic pathways in the control of food intake in humans and suggest involvement of 5-HT2c receptors in mediating the effects of human feeding behaviour.