Decrease in olfactory and taste receptor expression in the dorsolateral prefrontal cortex in chronic schizophrenia

Abstract

We have recently identified up- or down-regulation of the olfactory (OR) and taste (TASR) chemoreceptors 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 = 15) compared to control individuals (n = 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 neuropsychiatric 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 antipsychotics 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.

Keywords: Antipsychotics; Olfactory receptors; Prefrontal cortex; Schizophrenia; Taste receptors.