Abstract
Background: Postmortem studies have provided evidence for abnormalities of the γ-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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics.Arch Gen Psychiatry. 1995; 52: 258-266
- Postnatal development of parvalbumin immunoreactivity in axon terminals of basket and chandelier neurons in monkey neocortex.Prog Neuropsychopharmacol Biol Psychiatry. 1992; 16: 329-337
Bachus SE, Hyde TM, Herman MM, Eyan MF, Kleinman JE (1997): Abnormal cholecystokinin mRNA levels in entorhinal cortex of schizophrenics. J PsychiatrRes 31:233–256.
- Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics.Schizophr Res. 1997; 24: 349-355
- Two-dimensional versus three-dimensional cell counting.Trends Neurosci. 2001; 24: 11-17
- Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients.Arch Gen Psychiatry. 1991; 48: 996-1001
- Glutamate decarboxylase(65)-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain.J Chem Neuroanat. 2000; 20: 259-269
- Up-regulation of GABAA receptor binding on neurons of the prefrontal cortex in schizophrenic subjects.Neuroscience. 1996; 74: 1021-1031
- Regulation of calcium-binding protein immunoreactivity in GABA neurons of macaque primary visual cortex.Cereb Cortex. 1996; 6: 271-287
- Calbindin D-28K and parvalbumin in the rat nervous system.Neuroscience. 1990; 35: 375-475
- The density and spatial distribution of GABAergic neurons in the anterior cingulate cortex in major depressive disorder, bipolar disorder and schizophrenia.Biol Psychiatry. 2002; 51: 377-386
- Schizophrenia and anteroventral thalamic nucleus.Psychiatry Res. 1998; 82: 1-10
- Local circuit neurons of the prefrontal cortex in schizophrenia.Psychiatry Res. 1995; 59: 81-96
- Visualisation of chandelier cell axons by parvalbumin-immunoreactivity in monkey cerebral cortex.Proc Natl Acad Sci USA. 1989; 86: 2093-2097
- Parvalbumin immunoreactivity reveals layer IV of monkey cerebral cortex as a mosaic of microzones of thalamic afferent terminations.Brain Res. 1991; 562: 39-47
- Heterogeneity of GABAergic cells in cat visual cortex.J Neurosci. 1988; 8: 988-1000
- Effects of microwave pretreatment on immunocytochemical staining of vibratome sections and tissue blocks of human cerebral cortex stored in formaldehyde fixative for long periods.J Neurosci Methods. 1994; 55: 163-172
- Neuropeptide deficits in schizophrenia vs. Alzheimer’s disease cerebral cortex.Biol Psychiatry. 1996; 39: 82-91
- Decrease in reelin and glutamic acid decarboxylase 67 (GAD67) expression in schizophrenia and bipolar disorder.Arch Gen Psychiatry. 2000; 57: 1061-1069
- 3H-Muscimol binding sites are increased in autopsied brains of chronic schizophrenics.Life Sci. 1987; 40: 259-266
- Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques.J Histochem Cytochem. 1981; 29: 577-580
- Immunocytochemical localisation of calretinin in the forebrain of the rat.J Comp Neurol. 1991; 304: 198-218
Kalus P, Senitz D, Beckmann H (1997): Altered distribution of parvalbumin-immunoreactive local circuit neurons in the anterior cingulate cortex of schizophrenic patients. PsychiatryRes 75:49–59.
- Decrease in GABA immunoreactivity and alteration of GABA metabolism after kindling in the rat hippocampus.Exp Brain Res. 1989; 74: 375-386
- Heterogeneity of chandelier neurons in monkey neocortex.J Comp Neurol. 1990; 293: 599-615
- Regional brain concentrations of neuropeptides in Huntington’s chorea and schizophrenia.Science. 1983; 221: 972-975
- Cytoarchitectonic definition of prefrontal areas in the normal human cortex.Cereb Cortex. 1995; 5: 307-322
- GABAergic neuronal subtypes in the human frontal cortex—development and deficits in schizophrenia.J Chem Neuroanat. 2001; 22: 95-100
- Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin- or cholecystokinin-immunoreactive material.J Neurosci. 1984; 4: 2590-2603
- The Stanley foundation brain collection and neuropathology consortium.Schizophr Res. 2000; 44: 151-155
- Cholecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in schizophrenia.Biol Psychiatry. 1995; 37: 694-701
- Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical γ–aminobutyric acid neurons in subjects with schizophrenia.Arch Gen Psychiatry. 2000; 57: 237-245
- Schizophrenia and the parvalbumin-containing class of cortical local circuit neurons.Am J Psychiatry. 1997; 154: 1013-1015
- A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia.Proc Natl Acad Sci USA. 1998; 95: 5341-5346
- A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia.Schizophr Res. 2002; 55: 1-10
Article info
Publication history
Accepted:
February 11,
2002
Received in revised form:
December 10,
2001
Received in revised form:
February 1,
2002
Received:
July 23,
2001
Identification
Copyright
© 2002 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
