Serum Levels of PYY(1-36) Peptide in Patients with Schizophrenia on Clozapine Monotherapy

Abstract

Introduction: The present study was undertaken to determine if patients with schizophrenia on clozapine monotherapy have lower serum levels of peptide YY [PYY(1-36)], which is an endogenous inhibitor of food intake, comparing to healthy controls.

Methods: Data for 24 patients (mean age 38.8 years) with paranoid schizophrenia on clozapine monotherapy and 24 healthy subjects (gender- and age-matched; mean age 39.9 years) were analyzed.

Results: Fasting serum levels of PYY(1–36) were lower in the clozapine group (178.4±138.4 vs. 277.4±218.1 pg/mL, p=0.034). In the whole study sample PYY(1–36) levels were lower in subjects with body mass index≥25 kg/m² (p=0.03) and in subjects with abdominal obesity defined using International Diabetes Foundation criteria (p=0.04). There were no significant differences for metabolic syndrome, smoking, impaired fasting glucose, dyslipidemia, and homeostatic model assessment (HOMA) defined insulin resistance.

Discussion: Results suggest that weight is asso­ciated with levels of PYY. Patients on clozapine had higher body mass index, but not fat mass index or body weight, therefore lower levels of PYY(1–36) in patients taking clozapine may result from clozapine-induced weight gain and central ­obesity.

Key words

schizophrenia - clozapine - PYY - metabolic syndrome

• References

• 1 Mentlein R, Dahms P, Grandt D et al. Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV. Regul Pept 1993; 49: 133-144
• 2 Batterham RL, Cohen MA, Ellis SM et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003; 349: 941-948
• 3 Konturek PC, Konturek JW, Czesnikiewicz-Guzik M et al. Neuro-hormonal control of food intake: basic mechanisms and clinical implications. J Physiol Pharmacol 2005; 56 (Suppl. 06) 5-25
• 4 Onaga T, Zabielski R, Kato S. Multiple regulation of peptide YY secretion in the digestive tract. Peptides 2002; 23: 279-290
• 5 Stanley S, Wynne K, Bloom S. Gastrointestinal satiety signals III. Glucagon-like peptide 1, oxyntomodulin, peptide YY, and pancreatic polypeptide. Am J Physiol Gastrointest Liver Physiol 2004; 286: G693-G697
• 6 Glavas MM, Grayson BE, Allen SE et al. Characterization of brainstem peptide YY (PYY) neurons. J Comp Neurol 2008; 506: 194-210
• 7 Mitchell AJ, Vancampfort D, Sweers K et al. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders – a systematic review and meta-analysis. Schizophr Bull 2013; 39: 306-318
• 8 Wysokiński A, Kowman M, Kłoszewska I. The prevalence of metabolic syndrome and Framingham cardiovascular risk scores in adult inpatients taking antipsychotics – a retrospective medical records review. Psychiatr Danub 2012; 24: 314-322
• 9 Groop L, Orho-Melander M. The dysmetabolic syndrome. J Intern Med 2001; 250: 105-120
• 10 Bosy-Westphal A, Later W, Hitze B et al. Accuracy of bioelectrical impedance consumer devices for measurement of body composition in comparison to whole body magnetic resonance imaging and dual X-ray absorptiometry. Obes Facts 2008; 1: 319-324
• 11 Alberti KG, Zimmet P, Shaw J. Metabolic syndrome – a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006; 23: 469-480
• 12 Kelly TL, Wilson KE, Heymsfield SB. Dual energy X-Ray absorptiometry body composition reference values from NHANES. PLoS One 2009; 4: e7038
• 13 Vidarsdottir S, Roelfsema F, Streefland T et al. Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets. Eur J Endocrinol 2010; 162: 75-83
• 14 van der Zwaal EM, Merkestein M, Lam YK et al. The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature. Int J Obes (Lond) 2012; 36: 254-261
• 15 Weston-Green K, Huang XF, Deng C. Olanzapine treatment and metabolic dysfunction: a dose response study in female Sprague Dawley rats. Behav Brain Res 2011; 217: 337-346
• 16 Lin HC, Taylor IL. Release of peptide YY by fat in the proximal but not distal gut depends on an atropine-sensitive cholinergic pathway. Regulatory Peptides 2004; 117: 73-76
• 17 Pfluger PT, Kampe J, Castaneda TR et al. Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36. J Clin Endocrinol Metab 2007; 92: 583-588
• 18 Rahardjo GL, Huang XF, Tan YY et al. Decreased plasma peptide YY accompanied by elevated peptide YY and Y2 receptor binding densities in the medulla oblongata of diet-induced obese mice. Endocrinology 2007; 148: 4704-4710
• 19 Yang N, Wang C, Xu M et al. Interaction of dietary composition and PYY gene expression in diet-induced obesity in rats. J Huazhong Univ Sci Technolog Med Sci 2005; 25: 243-246
• 20 Alvarez Bartolome M, Borque M, Martinez-Sarmiento J et al. Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty. Obes Surg 2002; 12: 324-327
• 21 le Roux CW, Batterham RL, Aylwin SJ et al. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 2006; 147: 3-8
• 22 Guo Y, Ma L, Enriori PJ et al. Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans. Obesity (Silver Spring) 2006; 14: 1562-1570
• 23 Korner J, Inabnet W, Conwell IM et al. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity (Silver Spring) 2006; 14: 1553-1561