title: The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia.
abstract: BACKGROUND
  There is strong evidence for the presence of a deficit in cortical gamma aminobutyric acid (GABA) neurotransmission in schizophrenia. In this investigation we have used the calcium binding proteins (CBPs) parvalbumin (PV), calretinin (CR), and calbindin-D28K (CB) as markers of these neuronal populations, and have characterized their pattern and density in schizophrenia, bipolar disorder (BPD), and major depressive disorder (MDD).
  
  
  METHODS
  We examined the anterior cingulate cortex (ACC) in four groups of 15 brains each from subjects with schizophrenia, MDD, and BPD, and from control subjects. Using immunocytochemistry to identify these distinct neuronal populations, we quantified their areal density and spatial pattern organization.
  
  
  RESULTS
  There were reductions in the density of CB-labeled neurons in layer 2 in schizophrenia (34%; p =.04) and BPD (33%; p =.05) compared with control subjects; however, after correction for multiple comparisons these findings no longer attained formal statistical significance. We observed no differences in the density of the neuronal populations labeled by CR or PV in any layer of the cortex in any disorder compared with control subjects. There was increased clustering among PV-labeled neurons in BPD compared with control subjects but no significant differences in the spatial organization of the other neuronal subpopulations in any disorder.
  
  
  CONCLUSIONS
  The study provides some support for the presence of a deficit in GABAergic neurons in schizophrenia and shows that these changes are not specific to schizophrenia. The findings indicate that there may be a pathophysiological condition, shared by subjects with schizophrenia and BPD, which operates to selectively reduce the number or protein expression of CB-immunoreactive neurons.
authors.affiliation: Department of Psychological Medicine, Section of Experimental Neuropathology and PsychiatryInstitute of Psychiatry, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Cotter
authors.forename: Sabine
authors.initials: S
authors.lastname: Landau
authors.forename: Clare
authors.initials: C
authors.lastname: Beasley
authors.forename: Robert
authors.initials: R
authors.lastname: Stevenson
authors.forename: Gursharon
authors.initials: G
authors.lastname: Chana
authors.forename: Laura
authors.initials: L
authors.lastname: MacMillan
authors.forename: Ian
authors.initials: I
authors.lastname: Everall
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002452:Cell Count; D003865:Major Depressive Disorder / Q000473:pathology*; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D012559:Schizophrenia / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D005680:gamma-Aminobutyric Acid