Central dysregulations in the control of energy homeostasis and endocrine alterations in anorexia and bulimia nervosa J. Endocrinol. Invest. 30: 962-976, 2007 © 2007, Editrice Kurtis. © 2007, Editrice Kurtis 962 ABSTRACT. In the last decades we have come to understand that the hypothalamus is a key region in controlling energy homeostasis. A number of control models have been proposed to explain the regulation of feeding behavior in physiologi- cal and pathological conditions, but all those based on imbalances of single factors fail to ex- plain the disrupted regulation of energy supply in eating disorders such as anorexia nervosa and bulimia nervosa, as well as other psychiatric dis- orders. A growing amount of evidence demon- strates that many signaling molecules originated within the brain or coming from the adipose tis- sue or the gastro-enteric tract are involved in the highly complex process controlling food intake and energy expenditure. The recent discovery of leptin, ghrelin, and other factors have made it possible to penetrate in the still undefined patho- physiology of eating disorders with the hope of finding effective treatments for such diseases. (J. Endocrinol. Invest. 30: 962-976, 2007) © 2007, Editrice Kurtis INTRODUCTION Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are among the most common psychiatric illnesses in adolescents, and are a major cause of illness in the young popula- tion along with obesity and asthma (1). Many eating disorders (ED) are strongly influenced by psycho- logical pressures towards thinness and attractive- ness and are often characterized by distorted valu- ation of body shape and weight. In subjects ge- netically predisposed, environmental stressors might stimulate a trend toward modifications in the stress hormone system and in the general hormonal asset. Both starvation and overeating can be viewed as means to activate brain pathways that produce feelings of peace and euphoria, which fight against anxiety and depression. Interestingly, in most patients ED show temporal instability, since the diseases can move from active phase to recov- ery to relapse, and also from AN to BN syndrome and vice versa. This clinical observation has prompt- ed a key question: are ED a single syndrome with different manifestations? Many reports suggest that ED are a continuum going from AN to BN (2, 3). Given this instability between clinical syndromes, studies have more recently been focused on those features that herald the onset of the ED and are al- ready present in childhood (4). Peculiar features in temperament and character are frequently associ- ated with ED; in fact, women with AN are described as being neurotic, perfectionist, and obsessive, whereas women with BN are more impulsive and uninhibited than AN and healthy subjects (5). AN patients are often characterized by high harm avoidance and persistence, and low novelty seek- ing, reward dependence, self-directedness, where- as BN patients display high scores of harm avoid- ance, but also high novelty seeking, reward de- pendence, and low self directedness (6). Novelty seeking could be associated with the level of dopamine (DA) function in the mesolimbic- mesofrontal areas, whereas harm avoidance could be associated with serotonin (5-HT) function and a functional polymorphism in the promoter of the hu- man 5-HT transporter gene (7-9). Central alterations of norepinephrine (NE), DA and 5-HT functions have been repeatedly reported in AN and BN, both during the active phases of the diseases and after Key-words: Appetite, body weight, gut hormones, CNS, eating disorders. Correspondence: A. Torsello, MD, Department of Experimental Medicine, University of Milano-Bicocca, via Cadore 48, 20052 Monza, Italy. E-mail: antonio.torsello@unimib.it Accepted April 19, 2007. J. Endocrinol. Invest. 30: 962-976, 2007 A. Torsello 1,2 , F. Brambilla 3 , L. Tamiazzo 1 , I. Bulgarelli 1 , D. Rapetti 1 , E. Bresciani 1 , and V. Locatelli 1,2 1 Department of Experimental Medicine; 2 Interdepartmental Center for Bioinformatics and Proteomics, University of Milano-Bicocca, Monza; 3 Department of Mental Health, Sacco Hospital, Milan, Italy REVIEW ARTICLE