title: Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study.
abstract: 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.
authors.affiliation: Neuroanatomy Research Group, Institute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Uhrig
authors.affiliation: Neuroanatomy Research Group, Institute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Hirth
authors.affiliation: Neuroanatomy Research Group, Institute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Broccoli
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Bergische Landstrasse 2, 40629 Düsseldorf, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: von Wilmsdorff
authors.affiliation: Department of Neuropathology, University of Leipzig, Liebigstrasse 24, 04103 Leipzig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Institute of Neuropathology, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Sommer
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Zink
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frodl
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University (LMU) Munich, Nußbaumstrasse 7, 80336 München, Germany.
authors.forename: Berend
authors.initials: B
authors.lastname: Malchow
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University (LMU) Munich, Nußbaumstrasse 7, 80336 München, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Neuroanatomy Research Group, Institute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanagel
authors.affiliation: Neuroanatomy Research Group, Institute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Germany.
authors.forename: Anita C
authors.initials: AC
authors.lastname: Hansson
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University (LMU) Munich, Nußbaumstrasse 7, 80336 München, Germany; Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of Sao Paulo, Rua Dr. Ovidio Pires de Campos 785, 05453-010 São Paulo, SP, Brazil. Electronic address: Andrea.Schmitt@med.uni-muenchen.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018045:Receptors, Oxytocin / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; C569600:OXTR protein, human; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; C588222:oxytocin receptor, rat; D003024:Clozapine; D006220:Haloperidol
keywords: Antipsychotics; Gene expression; Oxytocin receptor; Post-mortem; Receptor autoradiography; Schizophrenia