We have developed a model suggesting that a confluence of the following four factors contribute to the susceptibility and natural history of anorexia nervosa and bulimia nervosa: (1) clinical and biochemical manifestations of obsessionalism; (2) a reduction in metabolic rate that interacts with obsessional features to produce a perseverative preoccupation with food intake and body image; (3) primary and/or secondary alterations in the neural mechanisms subserving hunger and satiety that reinforce pathological eating behaviors and; (4) an underlying depression that heightens the eating disordered patient's need to enhance low self-esteem by achieving an idealized body weight. In addition, we postulate that the abstinent bulimic experiences an unpleasant state of hypoarousal not dissimilar from that seen in the various forms of atypical depression that is ameliorated by the bingeing and purging process. We have focused our studies on the neurobiology of obsessionalism in the eating disorders and classic obsessive-compulsive disorder) OCD on three neurohormones, arginine vasopressin (AVP), corticotropin releasing hormone (CRH), and somatostatin. Our interest in AVP relates to the fact that administration of this neurohormone to experimental animals delays the extinction of behaviors acquired during aversive conditioning, an effect analogous to the obsessional patients' perseverative preoccupation with the potentially adverse consequences of relatively neutral stimuli or thoughts. Our data show that patients with classic OCD, bulimia nervosa, and anorexia nervosa all hypersecrete AVP into the CSF in association with profound disruptions of plasm AVP secretion. We also showed that among a wide range of antidepressants, only drugs preferentially capable of treating OCD (i.e. highly specific serotonin uptake inhibitors) significantly reduce AVP secretion into the CSF and diminish mRNA content and mRNA expression in the PVN of the rat hypothalamus. We also showed that these drugs also were unique in their capacity to reduce AVP release from rat hypothalamic organ culture. In addition to the hypersecretion of CSF AVP in classic OCD, we also found evidence of the hypersecretion of two other arousal producing neurohormones into the CSF, CRH and somatostatin. Our studies in patients with bulimia nervosa studied while actively bingeing and purging and following prolonged abstinence from these behaviors provide a model for the potential role of these behaviors in the economy of their illness.
