Decrease in olfactory and taste receptor expression in the dorsolateral prefrontal cortex in chronic schizophrenia Bel  en Ansoleaga a, 1 , Paula Garcia-Esparcia a, 1 , Raquel Pinacho b, c , Josep Maria Haro b, c , Bel  en Ramos b, c, * , Isidre Ferrer a, d, e, ** a Institut de Neuropatologia, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain b Unitat de Recerca, Parc Sanitari Sant Joan de D eu, Fundaci o Sant Joan de D eu, Universitat de Barcelona, Dr. Antoni Pujadas, 42, 08830, Sant Boi de Llobregat, Barcelona, Spain c Centro de Investigaci on Biom edica en Red de Salud Mental, CIBERSAM, Spain d Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, Spain e CIBERNED (Centro de Investigaci on Biom edica en Red de Enfermedades Neurodegenerativas), Spain article info Article history: Received 3 June 2014 Received in revised form 20 August 2014 Accepted 12 September 2014 Keywords: Schizophrenia Prefrontal cortex Olfactory receptors Taste receptors Antipsychotics abstract We have recently identified up- or down-regulation of the olfactory (OR) and taste (TASR) chemore- ceptors in the human cortex in several neurodegenerative diseases, raising the possibility of a general deregulation of these genes in neuropsychiatric disorders. In this study, we explore the possible deregulation of OR and TASR gene expression in the dorsolateral prefrontal cortex in schizophrenia. We used quantitative polymerase chain reaction on extracts from postmortem dorsolateral prefrontal cortex of subjects with chronic schizophrenia (n ¼ 15) compared to control individuals (n ¼ 14). Negative symptoms were evaluated premortem by the Positive and Negative Syndrome and the Clinical Global Impression Schizophrenia Scales. We report that ORs and TASRs are deregulated in the dorsolateral prefrontal cortex in schizophrenia. Seven out of eleven ORs and four out of six TASRs were down- regulated in schizophrenia, the most prominent changes of which were found in genes from the 11p15.4 locus. The expression did not associate with negative symptom clinical scores or the duration of the illness. However, most ORs and all TASRs inversely associated with the daily chlorpromazine dose. This study identifies for the first time a decrease in brain ORs and TASRs in schizophrenia, a neuro- psychiatric disease not linked to abnormal protein aggregates, suggesting that the deregulation of these receptors is associated with altered cognition of these disorders. In addition, the influence of antipsy- chotics on the expression of ORs and TASRs in schizophrenia suggests that these receptors could be involved in the mechanism of action or side effects of antipsychotics. © 2014 Elsevier Ltd. All rights reserved. 1. Introduction Ectopic expression of olfactory and taste receptors (ORs and TASRs, respectively) has been described in several organs and tis- sues (Behrens and Meyerhof, 2010; Branscomb et al., 2000; De la Cruz et al., 2009; Feldmesser et al., 2006; Li, 2013; Parmentier et al., 1992; Vanderhaeghen et al., 1997; Xu et al., 2013; Yamamoto and Ishimaru, 2013; Zhang et al., 2007). Their function in these locations is not known in most cases but it has been pro- posed that both ORs and TASRs play particular roles in autocrine, paracrine and endocrine signaling (Aggio et al., 2012; Deshpande et al., 2010; Dreyer, 1998; Fukuda et al., 2004; Griffin et al., 2009; Kang and Koo, 2012; Kinnamon, 2012; Spehr et al., 2003, 2004). A variety of compounds, mostly of unknown origin and function, can bind to autocrine receptors on the same cell, neighboring cells or distant cells. More recently, ORs and TASRs, and their down-stream effectors have been identified in the rodent and human brain (Dehkordi et al., 2012; Garcia-Esparcia et al., 2013; Grison et al., 2014; Otaki et al., 2004; Singh et al., 2011), with a widespread distribution although with regional variations (Garcia-Esparcia et al., 2013). Moreover, ORs are functionaldat least those * Corresponding author. Unitat de Recerca, Parc Sanitari Sant Joan de D eu, Fundaci o Sant Joan de D eu, Universitat de Barcelona, Centro de Investigaci on Bio- m edica en Red de Salud Mental, CIBERSAM, Dr. Antoni Pujadas 42, 08830 Sant Boi de Llobregat, Barcelona, Spain. Tel.: þ34 93 600 9452; fax: þ34 93 600 9771. ** Corresponding author. Institut de Neuropatologia, Servei Anatomia Patol ogica, Hospital Universitari de Bellvitge, Carrer Feixa Llarga sn, 08907 Hospitalet de Llo- bregat, Spain. Tel.: þ34 93 260 7452; fax: þ34 93 260 7503. E-mail addresses: bramos@fsjd.org (B. Ramos), 8082ifa@gmail.com (I. Ferrer). 1 These authors have contributed equally to this work. Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/psychires http://dx.doi.org/10.1016/j.jpsychires.2014.09.012 0022-3956/© 2014 Elsevier Ltd. All rights reserved. Journal of Psychiatric Research 60 (2015) 109e116