Current Drug Targets - CNS & Neurological Disorders, 2003, 2, 53-59 53 1568-007X/03 $41.00+.00 © 2003 Bentham Science Publishers Ltd. A Review of Neuropeptide and Neuroendocrine Dysregulation in Anorexia and Bulimia Nervosa Ursula F. Bailer and Walter H. Kaye * University of Pittsburgh Medical Center, Anorexia and Bulimia Nervosa Research Module, Western Psychiatric Institute & Clinic, 3811 O’Hara Street, 600 Iroquois Building, Pittsburgh, PA 15213, USA Abstract: Neuropeptides play an important role in the regulation of feeding behavior and obesity. The mechanisms for controlling food intake involve a complicated interplay between peripheral systems (including gustatory stimulation, gastrointestinal peptide secretion, and vagal afferent nerve responses) and central nervous system (CNS) neuropeptides and/or monoamines. These neuronal systems include neuropeptides (CRH, opioids, neuropeptide-Y (NPY) and peptide YY (PYY), vasopressin and oxytocin, CCK, and leptin) and monamines (serotonin, dopamine, norepinephrine). In addition to regulating eating behavior, a number of CNS neuropeptides participate in the regulation of neuroendocrine pathways. Thus, clinical studies have evaluated the possibility that CNS neuropeptide alterations may contribute to dysregulated secretion of the gonadal hormones, cortisol, thyroid hormones and growth hormone in the eating disorders. Most of the neuroendocrine and neuropeptide alterations apparent during symptomatic episodes of AN and BN tend to normalize after recovery. This observation suggests that most of the disturbances are consequences rather than causes of malnutrition, weight loss and/or altered meal patterns. Still, an understanding of these neuropeptide disturbances may shed light on why many people with AN or BN cannot easily "reverse" their illness and even after weight gain and normalized eating patterns, many individuals who have recovered from AN or BN have physiological, behavioral and psychological symptoms that persist for extended periods of time. Key Words: eating disorders, neuropeptides, neuroendocrinology, anorexia nervosa, bulimia nervosa. NEUROPEPTIDES The past decade has witnessed accelerating basic research on the role of neuropeptides in the regulation of feeding behavior and obesity. The mechanisms for controlling food intake involve a complicated interplay between peripheral systems (including gustatory stimulation, gastrointestinal peptide secretion, and vagal afferent nerve responses) and central nervous system (CNS) neuropeptides and/or monoamines. Thus, studies in animals show that neuropeptides, such as cholecystokinin, the endogenous opioids (such as beta-endorphin), and neuropeptide-Y, regulate the rate, duration, and size of meals, as well as macronutrient selection [1,2]. In addition to regulating eating behavior, a number of CNS neuropeptides participate in the regulation of neuroendocrine pathways. Thus, clinical studies have evaluated the possibility that CNS neuropeptide alterations may contribute to dysregulated secretion of the gonadal hormones, cortisol, thyroid hormones and growth hormone in the eating disorders [3,4]. While there are relatively few studies to date, most of the neuroendocrine and neuropeptide alterations apparent during symptomatic episodes of AN and BN tend to normalize after recovery. This observation suggests that most of the *Address correspondence to the author at the University of Pittsburgh Medical Center, Anorexia and Bulimia Nervosa Research Module, Western Psychiatric Institute & Clinic, 3811 O’Hara Street, 600 Iroquois Building, Pittsburgh, PA 15213, USA; Tel: (412) 647-9845; Fax: (412) 647- 9740; E-mail: kayewh@msx.upmc.edu disturbances are consequences rather than causes of malnutrition, weight loss and/or altered meal patterns. Still, an understanding of these neuropeptide disturbances may shed light on why many people with AN or BN cannot easily "reverse" their illness. In AN, malnutrition may contribute to a downward spiral sustaining and perpetuating the desire for more weight loss and dieting. Symptoms such as increased satiety, obsessions and dysphoric mood, may be exaggerated by these neuropeptide alterations and thus contribute to this downward spiral. Additionally, mutual interactions between neuropeptide, neuroendocrine and neurotransmitter pathways may contribute to the constellation of psychiatric comorbidity often observed in these disorders. Even after weight gain and normalized eating patterns, many individuals who have recovered from AN or BN have physiological, behavioral and psychological symptoms that persist for extended periods of time. Menstrual cycle dysregulation, for example, may persist for some months after weight restoration. The following sections provide a brief overview of studies of neuropeptides in AN and BN. OPIOID PEPTIDES Studies in laboratory animals raise the possibility that altered endogenous opioid activity might contribute to pathological feeding behavior in eating disorders since opioid agonists generally increase, and opioid antagonists decrease, food intake [5]. State-related reductions in concentrations of CSF beta-endorphin and related opiate