Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins.
BACKGROUND
Postmortem studies have provided evidence for abnormalities of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia, including deficits of GABA-containing interneurons. The calcium-binding proteins parvalbumin, calbindin, and calretinin can be used as markers for specific subpopulations of cortical GABAergic interneurons.


METHODS
Following our previous observation of a reduction in the density of parvalbumin- but not calretinin-immunoreactive cells in the prefrontal cortex (Brodmann area 10) in schizophrenia, we have quantified the laminar density of neurons immunoreactive for the calcium-binding proteins parvalbumin, calbindin, and calretinin in a further prefrontal cortical region (Brodmann area 9) in patients with schizophrenia, bipolar disorder, major depression, and in matched control subjects (each group n = 15).


RESULTS
Initial statistical analysis revealed reductions in the total cortical density of parvalbumin- and calbindin- but not calretinin-immunoreactive neurons in schizophrenia relative to control subjects. Further analysis comparing individual laminar densities between groups indicated that, following correction for multiple comparisons, only a reduction in calbindin-immunoreactive neurons in cortical layer II in the schizophrenic group attained statistical significance.


CONCLUSIONS
These findings suggest that deficits of specific GABAergic neurons, defined by the presence of calcium-binding proteins, are present in schizophrenia. Trends toward similar reductions are observed in bipolar disorder.
Beasley
Clare L
CL
Department of Biomedical Science, University of Sheffield, United Kingdom.
Zhang
Zhi J
ZJ
Patten
Iain
I
Reynolds
Gavin P
GP
D000328:Adult; D064032:Calbindin 2; D064026:Calbindins; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002452:Cell Count; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C576764:CALB2 protein, human; D064032:Calbindin 2; D064026:Calbindins; D002135:Calcium-Binding Proteins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid