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RESEARCH PRODUCT

Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study

Thomas FrodlJohann SteinerMartina Von WilmsdorffAndrea SchmittAndrea SchmittBerend MalchowRainer SpanagelMathias ZinkPeter FalkaiManfred BauerAnita C. HanssonNatalie HirthStefanie UhrigClemens SommerLaura Broccoli

subject

AdultMaleGene ExpressionVasotocinReal-Time Polymerase Chain ReactionLeft nucleusRats Sprague-Dawley03 medical and health scienceschemistry.chemical_compound0302 clinical medicinemedicineHaloperidolAnimalsHumansRNA MessengerClozapineBiological PsychiatryClozapineAgedAged 80 and overTemporal cortexBinding SitesBrainMiddle Agedmedicine.diseaseOxytocin receptor030227 psychiatryPsychiatry and Mental healthchemistryOxytocinReceptors OxytocinSchizophreniaSchizophreniaAutoradiographyHaloperidolFemalePsychologyNeurosciencehormones hormone substitutes and hormone antagonists030217 neurology & neurosurgeryAntipsychotic Agentsmedicine.drug

description

Schizophrenia is a severe neuropsychiatric disorder with impairments in social cognition. Several brain regions have been implicated in social cognition, including the nucleus caudatus, prefrontal and temporal cortex, and cerebellum. Oxytocin is a critical modulator of social cognition and the formation and maintenance of social relationships and was shown to improve symptoms and social cognition in schizophrenia patients. However, it is unknown whether the oxytocin receptor is altered in the brain. Therefore, we used qRT-PCR and Ornithine Vasotocin Analog ([125I]OVTA)-based receptor autoradiography to investigate oxytocin receptor expression at both the mRNA and protein level in the left prefrontal and middle temporal cortex, left nucleus caudatus, and right posterior superior vermis in 10 schizophrenia patients and 6 healthy controls. Furthermore, to investigate confounding effects of long-term antipsychotic medication we treated rats with clozapine or haloperidol for 12weeks and assessed expression of the oxytocin receptor in cortical and subcortical brain regions. In schizophrenia patients, we found a downregulation of oxytocin receptor mRNA in the temporal cortex and a decrease in receptor binding in the vermis. In the other regions, the results showed trends in the same direction, without reaching statistical significance. We found no differences between antipsychotic-treated rats and controls. Downregulated expression and binding of the oxytocin receptor in brain regions involved in social cognition may lead to a dysfunction of oxytocin signaling. Our results support a dysfunction of the oxytocin receptor in schizophrenia, which may contribute to deficits of social cognition.

https://doi.org/10.1016/j.schres.2016.04.019