Am J Psychiatry 156:1709-1719, November 1999
© 1999 American Psychiatric Association
Alterations in Chandelier Neuron Axon Terminals in the Prefrontal Cortex of Schizophrenic Subjects
Joseph N. Pierri, M.S., M.D.,
Adil S. Chaudry, B.S.,
Tsung-Ung W. Woo, M.D., Ph.D., and
David A. Lewis, M.D.
OBJECTIVE: Abnormalities in prefrontal cortical  -aminobutyric acid (GABA) neurotransmission may contribute to cognitive dysfunction in schizophrenia. The density of chandelier neuron axon terminals (cartridges) immunoreactive for the GABA membrane transporter (GAT-1) has been reported to be reduced in the dorsolateral prefrontal cortex of schizophrenic subjects. Because cartridges regulate the output of pyramidal cells, this study analyzed the laminar distribution of GAT-1-immunoreactive cartridges to determine whether certain subpopulations of pyramidal cells are preferentially affected. METHOD: Measurements were made of the density of GAT-1-immunoreactive cartridges in layers 2–3a, 3b–4, and 6 of dorsolateral prefrontal cortex area 46 in 30 subjects with schizophrenia, each of whom was matched to one normal and one psychiatric comparison subject. GAT-1-immunoreactive cartridge density was also examined in monkeys chronically treated with haloperidol. RESULTS: Relative to both comparison groups, the schizophrenic subjects had significantly lower GAT-1-immunoreactive cartridge density in layers 2–3a and 3b–4. The decrease was most common and most marked in layers 3b–4, where 80% of the schizophrenic subjects exhibited an average 50.1% decrease in cartridge density in comparison with the matched normal subjects. In contrast, GAT-1-immunoreactive cartridge density was unchanged in the haloperidol-treated monkeys. CONCLUSIONS: These findings demonstrate that the density of GAT-1-immunoreactive cartridges is reduced in the majority of schizophrenic subjects and that this alteration may most prominently affect the function of pyramidal cells located in the middle cortical layers. This abnormality may reflect a number of underlying deficits, including a primary defect in dorsolateral prefrontal cortex circuitry or a secondary response to altered thalamic input to this region.
This article has been cited by other articles:
|
|
|
|
 
G. Gonzalez-Burgos, D. C. Rotaru, A. V. Zaitsev, N. V. Povysheva, and D. A. Lewis
GABA Transporter GAT1 Prevents Spillover at Proximal and Distal GABA Synapses Onto Primate Prefrontal Cortex Neurons
J Neurophysiol,
February 1, 2009;
101(2):
533 - 547.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Gonzalez-Burgos and D. A. Lewis
GABA Neurons and the Mechanisms of Network Oscillations: Implications for Understanding Cortical Dysfunction in Schizophrenia
Schizophr Bull,
September 1, 2008;
34(5):
944 - 961.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Eggan, T. Hashimoto, and D. A. Lewis
Reduced Cortical Cannabinoid 1 Receptor Messenger RNA and Protein Expression in Schizophrenia
Arch Gen Psychiatry,
July 1, 2008;
65(7):
772 - 784.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Morris, T. Hashimoto, and D. A. Lewis
Alterations in Somatostatin mRNA Expression in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia or Schizoaffective Disorder
Cereb Cortex,
July 1, 2008;
18(7):
1575 - 1587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Vierling-Claassen, P. Siekmeier, S. Stufflebeam, and N. Kopell
Modeling GABA Alterations in Schizophrenia: A Link Between Impaired Inhibition and Altered Gamma and Beta Range Auditory Entrainment
J Neurophysiol,
May 1, 2008;
99(5):
2656 - 2671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. W. Wilson, O. O. Hernandez, R. M. Asherin, P. D. Teale, M. L. Reite, and D. C. Rojas
Cortical Gamma Generators Suggest Abnormal Auditory Circuitry in Early-Onset Psychosis
Cereb Cortex,
February 1, 2008;
18(2):
371 - 378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Menzies, C. Ooi, S. Kamath, J. Suckling, P. McKenna, P. Fletcher, E. Bullmore, and C. Stephenson
Effects of {gamma}-Aminobutyric Acid-Modulating Drugs on Working Memory and Brain Function in Patients With Schizophrenia
Arch Gen Psychiatry,
February 1, 2007;
64(2):
156 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. H. Woo and B. Lu
Regulation of Cortical Interneurons by Neurotrophins: From Development to Cognitive Disorders
Neuroscientist,
February 1, 2006;
12(1):
43 - 56.
[Abstract]
[PDF]
|
|
|
|
|
|
|
N. Pillai-Nair, A. K. Panicker, R. M. Rodriguiz, K. L. Gilmore, G. P. Demyanenko, J. Z. Huang, W. C. Wetsel, and P. F. Maness
Neural Cell Adhesion Molecule-Secreting Transgenic Mice Display Abnormalities in GABAergic Interneurons and Alterations in Behavior
J. Neurosci.,
May 4, 2005;
25(18):
4659 - 4671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Symond, A. W.F. Harris, E. Gordon, and L. M. Williams
"Gamma Synchrony" in First-Episode Schizophrenia: A Disorder of Temporal Connectivity?
Am J Psychiatry,
March 1, 2005;
162(3):
459 - 465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. Petrie, D. Schmidt, M. Bubser, J. Fadel, R. E. Carraway, and A. Y. Deutch
Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex
J. Neurosci.,
February 16, 2005;
25(7):
1629 - 1636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hashimoto, S. E. Bergen, Q. L. Nguyen, B. Xu, L. M. Monteggia, J. N. Pierri, Z. Sun, A. R. Sampson, and D. A. Lewis
Relationship of Brain-Derived Neurotrophic Factor and Its Receptor TrkB to Altered Inhibitory Prefrontal Circuitry in Schizophrenia
J. Neurosci.,
January 12, 2005;
25(2):
372 - 383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Cruz, S. M. Eggan, E. C. Azmitia, and D. A. Lewis
Serotonin1A Receptors at the Axon Initial Segment of Prefrontal Pyramidal Neurons in Schizophrenia
Am J Psychiatry,
April 1, 2004;
161(4):
739 - 742.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kromkamp, H. B. M. Uylings, M. P. Smidt, A. J. C. G. M. Hellemons, J. P. H. Burbach, and R. S. Kahn
Decreased Thalamic Expression of the Homeobox Gene DLX1 in Psychosis
Arch Gen Psychiatry,
September 1, 2003;
60(9):
869 - 874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hashimoto, D. W. Volk, S. M. Eggan, K. Mirnics, J. N. Pierri, Z. Sun, A. R. Sampson, and D. A. Lewis
Gene Expression Deficits in a Subclass of GABA Neurons in the Prefrontal Cortex of Subjects with Schizophrenia
J. Neurosci.,
July 16, 2003;
23(15):
6315 - 6326.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Morrow, J. D. Elsworth, and R. H. Roth
Axo-Axonic Structures in the Medial Prefrontal Cortex of the Rat: Reduction by Prenatal Exposure to Cocaine
J. Neurosci.,
June 15, 2003;
23(12):
5227 - 5234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Volk, J. N. Pierri, J.-M. Fritschy, S. Auh, A. R. Sampson, and D. A. Lewis
Reciprocal Alterations in Pre- and Postsynaptic Inhibitory Markers at Chandelier Cell Inputs to Pyramidal Neurons in Schizophrenia
Cereb Cortex,
October 1, 2002;
12(10):
1063 - 1070.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Sobell, M. J. Mikesell, and C. T. McMurray
Genetics and Etiopathophysiology of Schizophrenia
Mayo Clin. Proc.,
October 1, 2002;
77(10):
1068 - 1082.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. C. Goff
A 23-Year-Old Man With Schizophrenia
JAMA,
June 26, 2002;
287(24):
3249 - 3257.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. Middleton, K. Mirnics, J. N. Pierri, D. A. Lewis, and P. Levitt
Gene Expression Profiling Reveals Alterations of Specific Metabolic Pathways in Schizophrenia
J. Neurosci.,
April 1, 2002;
22(7):
2718 - 2729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Byne, M. S. Buchsbaum, L. A. Mattiace, E. A. Hazlett, E. Kemether, S. L. Elhakem, D. P. Purohit, V. Haroutunian, and L. Jones
Postmortem Assessment of Thalamic Nuclear Volumes in Subjects With Schizophrenia
Am J Psychiatry,
January 1, 2002;
159(1):
59 - 65.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. Pierri, C. L. E. Volk, S. Auh, A. Sampson, and D. A. Lewis
Decreased Somal Size of Deep Layer 3 Pyramidal Neurons in the Prefrontal Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry,
May 1, 2001;
58(5):
466 - 473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Kirkpatrick, R. W. Buchanan, D. E. Ross, and W. T. Carpenter Jr
A Separate Disease Within the Syndrome of Schizophrenia
Arch Gen Psychiatry,
February 1, 2001;
58(2):
165 - 171.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Lewis
Is There a Neuropathology of Schizophrenia? Recent Findings Converge on Altered Thalamic-Prefrontal Cortical Connectivity
Neuroscientist,
June 1, 2000;
6(3):
208 - 218.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. W. Volk, M. C. Austin, J. N. Pierri, A. R. Sampson, and D. A. Lewis
Decreased Glutamic Acid Decarboxylase67 Messenger RNA Expression in a Subset of Prefrontal Cortical {gamma}-Aminobutyric Acid Neurons in Subjects With Schizophrenia
Arch Gen Psychiatry,
March 1, 2000;
57(3):
237 - 245.
[Abstract]
[Full Text]
[PDF]
|
|
|
Get information about faster international access.
Privacy Policy
Copyright © 1999
American Psychiatric Association.
All rights reserved.
Home
| Search
| Current Issue
| Past Issues
| Subscribe
| All APPI Journals
| Help
| Contact Us
|
