+ Models PNEC-2124; No. of Pages 11 Please cite this article in press as: Garcia, F.D., et al., Anti-neuropeptide Y plasma immunoglobulins in relation to mood and appetite in depressive disorder. Psychoneuroendocrinology (2012), doi:10.1016/j.psyneuen.2012.01.015 Anti-neuropeptide Y plasma immunoglobulins in relation to mood and appetite in depressive disorder Frederico D. Garcia a , Quentin Coquerel a , Jean-Claude do Rego b , Aurore Cravezic b , Christine Bole-Feysot a , Evelyn Kiive c , Pierre De ´chelotte a , Jaanus Harro c , Sergueı ¨ O. Fetissov a, * a Nutrition, Gut and Brain Laboratory, Inserm U1073, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy, 76183, France b Experimental Neuropsychopharmacology Laboratory, CNRS FRE 2735, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy, 76183, France c Department of Psychology, Centre of Behavioral and Health Sciences, University of Tartu, Tartu, 50410, Estonia Received 26 October 2011; received in revised form 31 January 2012; accepted 31 January 2012 Psychoneuroendocrinology (2012) xxx, xxx—xxx KEYWORDS Mood disorders; Eating disorders; Obesity; Neuropeptides; Natural antibodies Summary Depression and eating disorders are frequently associated, but the molecular pathways responsible for co-occurrence of altered mood, appetite and body weight are not yet fully understood. Neuropeptide Y (NPY) has potent antidepressant and orexigenic properties and low central NPY levels have been reported in major depression. In the present study, we hypothesized that in patients with major depression alteration of mood, appetite and body weight may be related to NPY-reactive autoantibodies (autoAbs). To test this hypothesis, we compared plasma levels and affinities of NPY-reactive autoAbs between patients with major depression and healthy controls. Then, to evaluate if changes of NPY autoAb properties can be causally related to altered mood and appetite, we developed central and peripheral passive transfer models of human autoAbs in mice and studied depressive-like behavior in forced-swim test and food intake. We found that plasma levels of NPY IgG autoAbs were lower in patients with moderate but not with mild depression correlating negatively with the Montgomery—A ˚ sberg Depression Rating Scale scores and with immobility time of the forced-swim test in mice after peripheral injection of autoAbs. No significant differences in NPY IgG autoAb affinities between patients with depression and controls were found, but higher affinity of IgG autoAbs for NPY was associated with lower body mass index and prevented NPY-induced orexigenic response in mice after their central injection. These data suggest that changes of plasma levels of anti-NPY autoAbs are relevant to altered mood, while changes of their affinity may participate in altered appetite and body weight in patients with depressive disorder. # 2012 Elsevier Ltd. All rights reserved. * Corresponding author at: Inserm U1073, Faculte ´ de Me ´decine de Rouen, 22 Boulevard Gambetta, 76183 Rouen, France. Tel.: +332 35 14 82 55; fax: +332 35 14 82 26. E-mail address: Serguei.Fetissov@univ-rouen.fr (S.O. Fetissov). Available online at www.sciencedirect.com j our na l h omepa g e: www.e lse vie r.c om/l oca te/ psyne ue n 0306-4530/$ — see front matter # 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2012.01.015