Bulimia nervosa (BN) is an eating disorder of unknown etiology that most commonly occurs m women at normal weight. These women binge and purge and often have disturbances of mood and energy balance. When ill (symptomatic), BN women have been found to have alterations of a number of neurotransmitter systems (norepinephrine, serotonin, peptide YY (PYY), beta-endorphin, and cholecystokinin (CCK)). No studies have assessed the possibility that such disturbances may persist after recovery and thus are potentially trait-related. We will study the relationship of neurotransmitter alterations to pathological feeding, as well as mood and energy balance, in BN and determine whether neurotransmitter disturbances are state- and/or trait related.
Our first aim i s to determine whether alterations of serotonin and norepinephrine contribute to pathological feeding and disturbances of mood and energy balance in ill BN patients. BN patients may enter a vicious cycle in which pathological eating causes neurobiological changes in feeding and energy balance that sustains and perpetuates the illness. 20 ill BN and 20 matched control subjects will participate in each of these 3 studies: 1) We will use an acute tryptophan depletion paradigm to determine whether reduced plasma tryptophan/large neutral amino acid ratios, which theoretically reduces serotonin activity, reduces satiety and increases mood instability; 2) We will administer clonidine and 2-deoxy-glucose to determine whether increased alpha-2-noradrenoreceptor activity contributes to hyperphagia and mood instability; 3) We will determine whether reduced energy needs (which could promote weight gain and thus perpetuate pathological eating) is due to reduced sympathetic nervous system activity by measuring the plasma NE response to 2-deoxy-glucose and a test meal.
Our second aim i s to determine whether neurotransmitter and metabolic disturbances persist in BN subjects after recovery, As noted, such disturbances have only been characterized in ill BN patients. We will determine whether 24 recovered BN (compared to 24 matched controls) have: 1) Abnormal CSF concentrations of norepinephrine, PYY, beta-endorphin, and PYY; 2) Altered prolactin, feeding, and mood responses to administration of m-CPP, a serotonergic agonist; 3) Abnormal plasma CCK responses to a test meal; 4) Abnormal resting metabolism and metabolic/sympathetic response to a test meal. Considerable data in animals shows that feeding behavior is systematically regulated by a network of neuronal systems. We propose that feeding behavior is a system to be studied in human psychopathologic conditions, just as we study sleep or neuroendocrine systems, because of what these systems reveal about neurotransmitter activity. To do such studies, we have developed, in the initial grant period, a laboratory methodology that can assess the micro- and macrostructure of feeding in humans in relationship to physiological and psychological concomitants.
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