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Published in: Metabolic Brain Disease 2/2015

Open Access 01-04-2015 | Research Article

Serum levels of AgRP protein in patients with schizophrenia on clozapine monotherapy

Authors: Adam Wysokiński, Jakub Kaźmierski, Iwona Kłoszewska

Published in: Metabolic Brain Disease | Issue 2/2015

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Abstract

Aim: Agouti-related peptide (AgRP) is one of the hypothalamic hormones that works by increasing appetite and decreasing metabolism, thus leading to weight gain. The aim of the study was to find out if AgRP level in subjects with schizophrenia on clozapine monotherapy is higher compared with healthy controls. Methodology: We determined fasting serum AgRP levels in 24 subjects with schizophrenia on clozapine monotherapy and 24 healthy, age- and sex-matched controls. Biochemical and anthropometric measurements were combined with body composition analysis. Results: There was no difference for AgRP levels between patients taking clozapine and control group (15.00±8.65 vs. 15.33±6.82 pg/mL, p =0.37). We found negative correlations between AgRP levels and total body fat (r =−0.34 and −0.48 in the whole study group and clozapine group, respectively) and positive correlations with lean body mass (r =0.38 and 0.49 in the whole study group and clozapine group, respectively), body water (r =0.34 and 0.49 in the whole study group and clozapine group, respectively) and basal metabolic rate (r =0.42 both in the clozapine and control groups). There were no correlations with age, height, weight, body mass index, fat mass index, abdominal, waist or hip circumferences, waist-hip ratio, blood pressure, total cholesterol, HDL, LDL, triglycerides, uric acid, glucose, insulin, clozapine dose or treatment duration, duration of treatment with antipsychotics and markers for insulin resistance. Conclusion: We cannot conclude that treatment with clozapine is associated with increased level of AgRP. We did not find previously described differences in AgRP levels between obese and non-obese subjects or associations between AgRP and various metabolic parameters.
Literature
go back to reference Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome–a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 23:469–480CrossRefPubMed Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome–a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 23:469–480CrossRefPubMed
go back to reference Andrews ZB (2011) Central mechanisms involved in the orexigenic actions of ghrelin. Peptides 32:2248–2255CrossRefPubMed Andrews ZB (2011) Central mechanisms involved in the orexigenic actions of ghrelin. Peptides 32:2248–2255CrossRefPubMed
go back to reference Asenjo Lobos C, Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Leucht S (2010) Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev CD006633 Asenjo Lobos C, Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Leucht S (2010) Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev CD006633
go back to reference Bachmann CJ, Gebhardt S, Lehr D, Haberhausen M, Kaiser C, Otto B, Theisen FM (2012) Subjective and biological weight-related parameters in adolescents and young adults with schizophrenia spectrum disorder under clozapine or olanzapine treatment. Z Kinderchir 40:151–158 Bachmann CJ, Gebhardt S, Lehr D, Haberhausen M, Kaiser C, Otto B, Theisen FM (2012) Subjective and biological weight-related parameters in adolescents and young adults with schizophrenia spectrum disorder under clozapine or olanzapine treatment. Z Kinderchir 40:151–158
go back to reference Basoglu C, Oner O, Gunes C, Semiz UB, Ates AM, Algul A, Ebrinc S, Cetin M, Ozcan O, Ipcioglu O (2010) Plasma orexin A, ghrelin, cholecystokinin, visfatin, leptin and agouti-related protein levels during 6-week olanzapine treatment in first-episode male patients with psychosis. Int Clin Psychopharmacol 25:165–171CrossRefPubMed Basoglu C, Oner O, Gunes C, Semiz UB, Ates AM, Algul A, Ebrinc S, Cetin M, Ozcan O, Ipcioglu O (2010) Plasma orexin A, ghrelin, cholecystokinin, visfatin, leptin and agouti-related protein levels during 6-week olanzapine treatment in first-episode male patients with psychosis. Int Clin Psychopharmacol 25:165–171CrossRefPubMed
go back to reference Bosy-Westphal A, Later W, Hitze B, Sato T, Kossel E, Gluer CC, Heller M, Muller MJ (2008) 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 1:319–324PubMed Bosy-Westphal A, Later W, Hitze B, Sato T, Kossel E, Gluer CC, Heller M, Muller MJ (2008) 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 1:319–324PubMed
go back to reference Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B (2001) Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry 158:518–526CrossRefPubMed Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B (2001) Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry 158:518–526CrossRefPubMed
go back to reference Dipasquale S, Pariante CM, Dazzan P, Aguglia E, McGuire P, Mondelli V (2013) The dietary pattern of patients with schizophrenia: a systematic review. J Psychiatr Res 47:197–207CrossRefPubMed Dipasquale S, Pariante CM, Dazzan P, Aguglia E, McGuire P, Mondelli V (2013) The dietary pattern of patients with schizophrenia: a systematic review. J Psychiatr Res 47:197–207CrossRefPubMed
go back to reference Druce MR, Small CJ, Bloom SR (2004) Minireview: Gut peptides regulating satiety. Endocrinology 145:2660–2665CrossRefPubMed Druce MR, Small CJ, Bloom SR (2004) Minireview: Gut peptides regulating satiety. Endocrinology 145:2660–2665CrossRefPubMed
go back to reference Ehrlich S, Leopold K, Merle JV, Theophil I, Haag W, Lautenschlager M, Schaefer M (2012) Trajectories of agouti-related protein and leptin levels during antipsychotic-associated weight gain in patients with schizophrenia. J Clin Psychopharmacol 32:767–772CrossRefPubMed Ehrlich S, Leopold K, Merle JV, Theophil I, Haag W, Lautenschlager M, Schaefer M (2012) Trajectories of agouti-related protein and leptin levels during antipsychotic-associated weight gain in patients with schizophrenia. J Clin Psychopharmacol 32:767–772CrossRefPubMed
go back to reference Ferno J, Varela L, Skrede S, Vazquez MJ, Nogueiras R, Dieguez C, Vidal-Puig A, Steen VM, Lopez M (2011) Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation. PLoS One 6:e20571CrossRefPubMedCentralPubMed Ferno J, Varela L, Skrede S, Vazquez MJ, Nogueiras R, Dieguez C, Vidal-Puig A, Steen VM, Lopez M (2011) Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation. PLoS One 6:e20571CrossRefPubMedCentralPubMed
go back to reference Fontaine KR, Heo M, Harrigan EP, Shear CL, Lakshminarayanan M, Casey DE, Allison DB (2001) Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate. Psychiatry Res 101:277–288CrossRefPubMed Fontaine KR, Heo M, Harrigan EP, Shear CL, Lakshminarayanan M, Casey DE, Allison DB (2001) Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate. Psychiatry Res 101:277–288CrossRefPubMed
go back to reference Gavrila A, Chan JL, Miller LC, Heist K, Yiannakouris N, Mantzoros CS (2005) Circulating melanin-concentrating hormone, agouti-related protein, and alpha-melanocyte-stimulating hormone levels in relation to body composition: alterations in response to food deprivation and recombinant human leptin administration. J Clin Endocrinol Metab 90:1047–1054CrossRefPubMed Gavrila A, Chan JL, Miller LC, Heist K, Yiannakouris N, Mantzoros CS (2005) Circulating melanin-concentrating hormone, agouti-related protein, and alpha-melanocyte-stimulating hormone levels in relation to body composition: alterations in response to food deprivation and recombinant human leptin administration. J Clin Endocrinol Metab 90:1047–1054CrossRefPubMed
go back to reference Hagan MM, Rushing PA, Pritchard LM, Schwartz MW, Strack AM, Van Der Ploeg LH, Woods SC, Seeley RJ (2000) Long-term orexigenic effects of AgRP-(83–132) involve mechanisms other than melanocortin receptor blockade. Am J Physiol Regul Integr Comp Physiol 279:R47–R52PubMed Hagan MM, Rushing PA, Pritchard LM, Schwartz MW, Strack AM, Van Der Ploeg LH, Woods SC, Seeley RJ (2000) Long-term orexigenic effects of AgRP-(83–132) involve mechanisms other than melanocortin receptor blockade. Am J Physiol Regul Integr Comp Physiol 279:R47–R52PubMed
go back to reference Kane JM (2012) Addressing nonresponse in schizophrenia. J Clin Psychiatry 73:e07PubMed Kane JM (2012) Addressing nonresponse in schizophrenia. J Clin Psychiatry 73:e07PubMed
go back to reference Katsuki A, Sumida Y, Gabazza EC, Murashima S, Tanaka T, Furuta M, Araki-Sasaki R, Hori Y, Nakatani K, Yano Y, Adachi Y (2001) Plasma levels of agouti-related protein are increased in obese men. J Clin Endocrinol Metab 86:1921–1924CrossRefPubMed Katsuki A, Sumida Y, Gabazza EC, Murashima S, Tanaka T, Furuta M, Araki-Sasaki R, Hori Y, Nakatani K, Yano Y, Adachi Y (2001) Plasma levels of agouti-related protein are increased in obese men. J Clin Endocrinol Metab 86:1921–1924CrossRefPubMed
go back to reference Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL (2003) H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28:519–526CrossRefPubMed Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL (2003) H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28:519–526CrossRefPubMed
go back to reference Moriya J, Takimoto Y, Yoshiuchi K, Shimosawa T, Akabayashi A (2006) Plasma agouti-related protein levels in women with anorexia nervosa. Psychoneuroendocrinology 31:1057–1061CrossRefPubMed Moriya J, Takimoto Y, Yoshiuchi K, Shimosawa T, Akabayashi A (2006) Plasma agouti-related protein levels in women with anorexia nervosa. Psychoneuroendocrinology 31:1057–1061CrossRefPubMed
go back to reference Morton GJ, Schwartz MW (2001) The NPY/AgRP neuron and energy homeostasis. Int J Obes Relat Metab Disord 25(Suppl 5):S56–S62CrossRefPubMed Morton GJ, Schwartz MW (2001) The NPY/AgRP neuron and energy homeostasis. Int J Obes Relat Metab Disord 25(Suppl 5):S56–S62CrossRefPubMed
go back to reference Newcomer JW (2005) Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19(Suppl 1):1–93PubMed Newcomer JW (2005) Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19(Suppl 1):1–93PubMed
go back to reference Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, Barsh GS (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278:135–138CrossRefPubMed Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, Barsh GS (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278:135–138CrossRefPubMed
go back to reference Olofsson LE, Unger EK, Cheung CC, Xu AW (2013) Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance. Proc Natl Acad Sci U S A 110:E697–E706CrossRefPubMedCentralPubMed Olofsson LE, Unger EK, Cheung CC, Xu AW (2013) Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance. Proc Natl Acad Sci U S A 110:E697–E706CrossRefPubMedCentralPubMed
go back to reference Rasmussen H, Ebdrup BH, Oranje B, Pinborg LH, Knudsen GM, Glenthoj B (2014) Neocortical serotonin2A receptor binding predicts quetiapine associated weight gain in antipsychotic-naive first-episode schizophrenia patients. Int J Neuropsychopharmacol 1–8 Rasmussen H, Ebdrup BH, Oranje B, Pinborg LH, Knudsen GM, Glenthoj B (2014) Neocortical serotonin2A receptor binding predicts quetiapine associated weight gain in antipsychotic-naive first-episode schizophrenia patients. Int J Neuropsychopharmacol 1–8
go back to reference Schwartz MW, Woods SC, Porte DJ, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661–671PubMed Schwartz MW, Woods SC, Porte DJ, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661–671PubMed
go back to reference Sentissi O, Epelbaum J, Olie JP, Poirier MF (2008) Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review. Schizophr Bull 34:1189–1199CrossRefPubMedCentralPubMed Sentissi O, Epelbaum J, Olie JP, Poirier MF (2008) Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review. Schizophr Bull 34:1189–1199CrossRefPubMedCentralPubMed
go back to reference Shutter JR, Graham M, Kinsey AC, Scully S, Luthy R, Stark KL (1997) Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev 11:593–602CrossRefPubMed Shutter JR, Graham M, Kinsey AC, Scully S, Luthy R, Stark KL (1997) Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev 11:593–602CrossRefPubMed
go back to reference Staszkiewicz J, Horswell R, Argyropoulos G (2007) Chronic consumption of a low-fat diet leads to increased hypothalamic agouti-related protein and reduced leptin. Nutrition 23:665–671CrossRefPubMedCentralPubMed Staszkiewicz J, Horswell R, Argyropoulos G (2007) Chronic consumption of a low-fat diet leads to increased hypothalamic agouti-related protein and reduced leptin. Nutrition 23:665–671CrossRefPubMedCentralPubMed
go back to reference Wetterling T (2001) Bodyweight gain with atypical antipsychotics. A comparative review. Drug Saf 24:59–73CrossRefPubMed Wetterling T (2001) Bodyweight gain with atypical antipsychotics. A comparative review. Drug Saf 24:59–73CrossRefPubMed
go back to reference Wysokiński A, Kowalski ML, Kłoszewska I (2014) Serum levels of desacyl ghrelin in patients with schizophrenia on clozapine monotherapy. Psychiatry Clin Neurosci [Epub ahead of print]. Wysokiński A, Kowalski ML, Kłoszewska I (2014) Serum levels of desacyl ghrelin in patients with schizophrenia on clozapine monotherapy. Psychiatry Clin Neurosci [Epub ahead of print].
Metadata
Title
Serum levels of AgRP protein in patients with schizophrenia on clozapine monotherapy
Authors
Adam Wysokiński
Jakub Kaźmierski
Iwona Kłoszewska
Publication date
01-04-2015
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 2/2015
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-014-9592-6

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