Abstract The aim of this study was to examine whether anorexia nervosa and bulimia nervosa are accompanied by lower serum activity of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5), a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-ter- minus of oligo- and polypeptides. Substrates of DPP IV are, amongst others, neuroactive eptides, such as sub- stance P, growth hormone releasing hormone, neuropep- tide Y, and peptide YY. DPP IV activity was measured in the serum of 21 women with anorexia nervosa, 21 women with bulimia nervosa and 18 normal women. Serum DPP IV activity was significantly lower in patients with anorexia nervosa and bulimia nervosa than in the normal controls. In the total study group, there were significant and inverse relationships between serum DPP IV activity and the total scores on the Bulimic Investigatory Test, Ed- inburgh, the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale. In the total study group no significant correlations between DPP IV and age, body weight or body mass index could be found. It is concluded that lowered serum DPP IV activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesised that a combined dysregulation of DPP IV and neuroactive peptides, which are substrates of DPP IV, e.g. neuropeptide Y and peptide YY, could be an inte- gral component of eating disorders. Key words Anorexia · Bulimia · Peptidases · Dipeptidyl peptidase IV · Neuropeptides Introduction Dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5) is a mem- brane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo- and poly- peptides under definite structural conditions (De Meester 1992, 1999; Hopsu-Havu and Glenner 1966; Van Hoof et al. 1992). DPP IV is widely distributed among human tis- sues and body fluids, including serum, the hypophysial portal system and the brain (Hopsu-Havu and Glenner 1966; Kato et al. 1978; Bernstein et al. 1987; Maes et al. 1994; Van Hoof et al. 1992). DPP IV has an important role in the processing of polypeptides and proteins, in- testinal assimilation, renal handling of proline containing peptides,and adhesion and modulation of immune reactiv- ity (Yaron and Naider 1993; Morimoto and Schlossman 1998; De Meester et al. 1999). The cleavage of peptides by DPP IV can result in activation, inactivation or in a changed activity of peptides (Heymann and Mentlein 1978). DPP IV can process neuroactive peptides (neu- ropeptides), such as substance P, growth hormone releas- ing hormone (GHRH), neuropeptide Y and peptide YY (Conlon and Sheehan 1983; Frohman et al. 1989; Mentlein et al. 1993; Zukowska-Grojec 1997). On the T cell surface, DPP IV has been proven to be identical with the CD26 molecule and its expression is in- creased together with that of other activation markers, e.g. HLA-DR (Barton et al. 1990; Iwaki-Egawa et al. 1995; Mattern et al. 1991; Scholz et al. 1985). The origin of plasma DPP IV activity is, in part, determined by periph- eral tissues, such as the liver, T lymphocytes, endothelial Dirk van West · Palmiero Monteleone · Antonello Di Lieto · Ingrid De Meester · Christine Durinx · Simon Scharpe · Aihua Lin · Mario Maj · Michael Maes Lowered Serum dipeptidyl peptidase IV activity in patients with anorexia and bulimia nervosa Eur Arch Psychiatry Clin Neurosci (2000) 250 : 86–92 © Steinkopff Verlag 2000 Received: 29 June 1999 / Accepted: 3 January 2000 ORIGINAL PAPER D. van West · A. Lin · M. Maes Clinical Research Center for Mental Health (CRC-MH), Antwerp, Belgium P. Monteleone · A. Di Lieto · M. Maj Department of Psychiatry, Universita’ di Napoli, Italy I. De Meester · C. Durinx · S. Scharpe Department of Clinical Biochemistry, University of Antwerp, Wilrijk, Belgium M. Maes IRCCS, Istituto Fatebenefratelli, Brescia, Italy M. Maes Department of Psychiatry, Vanderbilt University, Nashville, USA M. Maes, M.D., Ph.D. () Professor and Chairman Department of Psychiatry & Neuropsychology, University Hospital of Maastrich, Postbus 5800, 6202 AZ Maastrich, The Netherlands e-mail: crc-mh@online.be, Fax: 0032-89-723531