title: Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics.
abstract: BACKGROUND
  Metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5) are novel therapeutic targets for major depression (MD), bipolar disorder (BD) and schizophrenia. We aimed to determine whether mGluR2/3 and mGluR5 binding in the anterior cingulate cortex (ACC), a brain region essential for the regulation of mood, cognition and emotion, were differentially altered in these pathologies.
  
  
  METHODS
  Using postmortem human brains derived from 2 cohorts, [(3)H]LY341495 binding to mGluR2/3 and [(3)H]MPEP binding to mGluR5 were measured by receptor autoradiography in the ACC. The first cohort comprised samples from individuals who had MD with psychosis (MDP), MD without psychosis (MDNP) and matched controls (n = 11-12 per group). The second cohort comprised samples from individuals who had MDNP, BD, schizophrenia and matched controls (n = 15 per group).
  
  
  RESULTS
  No differences in mGluR2/3 or mGluR5 binding were observed in the MDP, MDNP, BD or schizophrenia groups compared with the control group (all p > 0.05). Importantly, there were also no differences in binding densities between the psychiatric disorders (p > 0.05). We did, however, observe age-related effects, with consistent negative associations between mGluR2/3 and age in the control group (r < -0.575, p < 0.025) and the psychotic disorder groups (MDP and schizophrenia: r = -0.765 to -0.515, p < 0.05), but not in the mood disorder groups (MDNP, BD).
  
  
  CONCLUSIONS
  Replication in larger independent cohorts and medication-naive individuals would strengthen these findings.
  
  
  CONCLUSIONS
  Our findings suggest that mGluRs are unaltered in the ACC; however, the presence of altered receptor function cannot be discounted and requires further investigation. Taken together with previous studies, which report differential changes in mGluR2, 3 and 5 across these disorders, we suggest mGluRs may be affected in a brain region-specific manner.
authors.affiliation: The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Illawarra Health and Medical Research Institute, Wollongong, New South Wales, and Schizophrenia Research Institute, Sydney, New South Wales, Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Matosin
authors.affiliation: The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Schizophrenia Research Institute, Sydney, New South Wales, and School of Psychology, Faculty of Social Science, University of Wollongong, New South Wales, Australia.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fernandez-Enright
authors.affiliation: The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Illawarra Health and Medical Research Institute, Wollongong, New South Wales, and Schizophrenia Research Institute, Sydney, New South Wales, Australia.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Frank
authors.affiliation: The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Illawarra Health and Medical Research Institute, Wollongong, New South Wales, and Schizophrenia Research Institute, Sydney, New South Wales, Australia.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: Wong
authors.affiliation: The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Illawarra Health and Medical Research Institute, Wollongong, New South Wales, and Schizophrenia Research Institute, Sydney, New South Wales, Australia.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Illawarra Health and Medical Research Institute, Wollongong, New South Wales, and Schizophrenia Research Institute, Sydney, New South Wales, Australia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Newell
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism; D001345:Autoradiography; D001714:Bipolar Disorder / Q000378:metabolism*; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D055815:Young Adult
chemical_list: C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3