Dysregulation of glutamate carboxypeptidase II in psychiatric disease

Tomás R. Guilarte, Dima Hammoud, Jennifer L. McGlothan, Brian S. Caffo, Catherine A. Foss, Alan P. Kozikowski, Martin G. Pomper

Research output: Contribution to journalArticle

Abstract

Experimental evidence is beginning to converge on an important role for dysregulation of glutamate carboxypeptidase II (GCPII) in schizophrenia. The goal of this study was to determine GCPII levels in postmortem brain specimens of patients with schizophrenia, bipolar disorder or unipolar depression and age-matched control subjects. We used N-[N-(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[125I]iodo-l-tyrosine ([125I]DCIT), a high-affinity radioligand for GCPII, to probe for GCPII expression in prefrontal cortex (PFC) and mesial temporal lobe, two brain regions implicated in the pathophysiology of schizophrenia. We found that GCPII levels measured by [125I]DCIT quantitative autoradiography were significantly lower in the PFC and entorhinal cortex in patients with schizophrenia compared to age-matched controls. Patients with bipolar disorder also expressed significantly lower GCPII levels in PFC than controls. The decrease in [125I]DCIT binding in schizophrenia and bipolar disorder remained significant after adjusting for drug abuse. A significant difference in GCPII levels was also observed between schizophrenia relative to bipolar disorder and depressed subjects in the hippocampus-stratum lucidum and between schizophrenia and bipolar in the CA2 region of the hippocampus, with bipolar and depressed subjects expressing higher levels of GCPII than subjects with schizophrenia. These differences in hippocampal GCPII levels may implicate differences in the etiologies of these mental disorders. In summary, this study demonstrates a regional dysregulation of GCPII expression in the brain of patients with schizophrenia and other psychiatric disorders and supports a hypoglutamatergic state of the former illness. GCPII may represent a viable therapeutic target for intervention in psychiatric disease.

Original languageEnglish (US)
Pages (from-to)324-332
Number of pages9
JournalSchizophrenia Research
Volume99
Issue number1-3
DOIs
StatePublished - Feb 1 2008

Keywords

  • Bipolar disorder
  • Depression
  • GCPII
  • Human brain
  • Imaging
  • NAALADase
  • Schizophrenia
  • [I]DCIT

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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