Neurochemical correlates of cortical GABAergic deficits in schizophrenia: selective losses of calcium binding protein immunoreactivity.
Deficits in a variety of different neurochemical species are consistent with a loss of cortical gamma-aminobutyric acid (GABA)ergic interneurons in schizophrenia. As well as neurochemical markers that indicate all neurons using GABA as a transmitter, and which include GABA uptake sites and glutamate decarboxylase, deficits of certain neuropeptides and calcium binding proteins coexisting with GABA have been reported. These abnormalities are indicative of losses specific to certain subtypes of GABAergic neurons. The calcium binding proteins in particular demonstrate selective deficits; we find losses of parvalbumin- and calbindin-, but not calretinin-immunoreactive cells in the prefrontal cortex in schizophrenia. These selective reductions in the density of parvalbumin- and calbindin-containing neurons could reflect functional loss of expression in intact cells or alternatively a deficit in the density of certain GABAergic neuronal subtypes. The latter interpretation is consistent with a neurodevelopmental pathogenesis involving neuronal damage at a time prior to the expression of these protective calcium-binding proteins. In this review we discuss the evidence for altered GABAergic transmission in schizophrenia.
Reynolds
G P
GP
Department of Biomedical Science, University of Sheffield, Sheffield, UK. g.p.reynolds@sheffield.ac.uk
Zhang
Z J
ZJ
Beasley
C L
CL
D015415:Biomarkers / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009433:Neural Inhibition / Q000502:physiology; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D005680:gamma-Aminobutyric Acid