This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Schahram Akbarian, MD, PhD; James J. Kim; Steven G. Pothin, MD; William P. Hetrick, PhD; William E. Bunney, Jr, MD; Edward G. Jones, MD, PhD

Arch Gen Psychiatry. 1996;53(5):425-436.

Abstract
Background
The cortical subplate is a transitory structure involved in the formation of connections in developing cerebral cortex. Interstitial neurons, normally present in subcortical white matter (WM) of the adult brain, have escaped the programmed cell death that eliminates most subplate neurons. Previous investigations indicated a maldistribution of one population of interstitial neurons in the WM of brains of schizophrenic patients, suggesting a defect of the subplate during brain development.

Methods
Three histochemically or immunocytochemically defined neuronal populations were studied in WM beneath the middle frontal gyrus of 20 schizophrenic patients and 20 matched control subjects.

Results
Brains of schizophrenic patients showed significant changes in the distribution of the three neuronal populations: microtubule-associated protein 2 and nonphosphorylated neurofilament-immunoreactive neurons showed a decreased density in superficial WM and an increased density in deeper WM. Nicotinamide adenine dinucleotide phosphate—diaphorase neurons were reduced in superficial WM and showed variable densities in deeper WM. Thirty-five percent of the brains of schizophrenic patients but no brains of the control subjects showed a maldistribution of neurons toward deeper WM with at least two of the three markers. Changes in neuronal distribution were not linked to age, gender, autolysis time, or subtype of schizophrenia.

Conclusions
Selective displacement of interstitial WM neurons in the frontal lobe of brains of schizophrenic patients may indicate alteration in the migration of subplate neurons or in the pattern of programmed cell death. Both could lead to defective cortical circuitry in the brains of schizophrenic patients.

Author Affiliations
From the Departments of Anatomy and Neurobiology (Drs Akbarian and Jones and Mr Kim) and Psychiatry and Human Behavior (Drs Potkin, Hetrick, and Bunney), University of California, Irvine.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Mice with Altered Myelin Proteolipid Protein Gene Expression Display Cognitive Deficits Accompanied by Abnormal Neuron-Glia Interactions and Decreased Conduction Velocities
Tanaka et al.
J. Neurosci. 2009;29:8363-8371.
ABSTRACT | FULL TEXT  

White matter microstructure in schizophrenia: effects of disorder, duration and medication
Kanaan et al.
Br. J. Psychiatry 2009;194:236-242.
ABSTRACT | FULL TEXT  

Disrupted-in-schizophrenia 1 and neuregulin 1 are required for the specification of oligodendrocytes and neurones in the zebrafish brain
Wood et al.
Hum Mol Genet 2009;18:391-404.
ABSTRACT | FULL TEXT  

A Genome-Wide Association Study of Schizophrenia Using Brain Activation as a Quantitative Phenotype
Potkin et al.
Schizophr Bull 2009;35:96-108.
ABSTRACT | FULL TEXT  

Neurogenesis in the chronic lesions of multiple sclerosis
Chang et al.
Brain 2008;131:2366-2375.
ABSTRACT | FULL TEXT  

Cortical white-matter microstructure in schizophrenia: Diffusion imaging study
ANDREONE et al.
Br. J. Psychiatry 2007;191:113-119.
ABSTRACT | FULL TEXT  

Connections in Schizophrenia
Lim
Am. J. Psychiatry 2007;164:995-998.
FULL TEXT  

Relative Glucose Metabolic Rate Higher in White Matter in Patients With Schizophrenia
Buchsbaum et al.
Am. J. Psychiatry 2007;164:1072-1081.
ABSTRACT | FULL TEXT  

Endogenous Neuregulin Restores Radial Glia in a (Ferret) Model of Cortical Dysplasia
Gierdalski et al.
J. Neurosci. 2005;25:8498-8504.
ABSTRACT | FULL TEXT  

Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal Cortex of Subjects With Schizophrenia
Akbarian et al.
Arch Gen Psychiatry 2005;62:829-840.
ABSTRACT | FULL TEXT  

White Matter Abnormalities in First-Episode Schizophrenia or Schizoaffective Disorder: A Diffusion Tensor Imaging Study
Szeszko et al.
Am. J. Psychiatry 2005;162:602-605.
ABSTRACT | FULL TEXT  

A comprehensive analysis of 22q11 gene expression in the developing and adult brain
Maynard et al.
Proc. Natl. Acad. Sci. USA 2003;100:14433-14438.
ABSTRACT | FULL TEXT  

Schizophrenia
Freedman
NEJM 2003;349:1738-1749.
FULL TEXT  

Investigation of White Matter Structure in Velocardiofacial Syndrome: A Diffusion Tensor Imaging Study
Barnea-Goraly et al.
Am. J. Psychiatry 2003;160:1863-1869.
ABSTRACT | FULL TEXT  

White Matter Changes in Schizophrenia: Evidence for Myelin-Related Dysfunction
Davis et al.
Arch Gen Psychiatry 2003;60:443-456.
ABSTRACT | FULL TEXT  

Microarray Technology: A Review of New Strategies to Discover Candidate Vulnerability Genes in Psychiatric Disorders
Bunney et al.
Am. J. Psychiatry 2003;160:657-666.
ABSTRACT | FULL TEXT  

Perinatal Neurosteroid Levels Influence GABAergic Interneuron Localization in Adult Rat Prefrontal Cortex
Grobin et al.
J. Neurosci. 2003;23:1832-1839.
ABSTRACT | FULL TEXT  

Distribution of Microtubule-Associated Protein MAP2-Immunoreactive Interstitial Neurons in the Parahippocampal White Matter in Subjects With Schizophrenia
Rioux et al.
Am. J. Psychiatry 2003;160:149-155.
ABSTRACT | FULL TEXT  

A Computational Morphometric MRI Study of Schizophrenia: Effects of Hallucinations
Shapleske et al.
Cereb Cortex 2002;12:1331-1341.
ABSTRACT | FULL TEXT  

Expression of Kynurenine Aminotransferase in the Subplate of the Rat and Its Possible Role in the Regulation of Programmed Cell Death
Csillik et al.
Cereb Cortex 2002;12:1193-1201.
ABSTRACT | FULL TEXT  

Expression of Oct-6, a POU III Domain Transcription Factor, in Schizophrenia
Ilia et al.
Am. J. Psychiatry 2002;159:1174-1182.
ABSTRACT | FULL TEXT  

Uncinate Fasciculus Findings in Schizophrenia: A Magnetic Resonance Diffusion Tensor Imaging Study
Kubicki et al.
Am. J. Psychiatry 2002;159:813-820.
ABSTRACT | FULL TEXT  

Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse
Liu et al.
Proc. Natl. Acad. Sci. USA 2001;98:3477-3482.
ABSTRACT | FULL TEXT  

Is There a Neuropathology of Schizophrenia? Recent Findings Converge on Altered Thalamic-Prefrontal Cortical Connectivity
Lewis
Neuroscientist 2000;6:208-218.
ABSTRACT  

Volumetric Measure of the Frontal and Temporal Lobe Regions in Schizophrenia: Relationship to Negative Symptoms
Sanfilipo et al.
Arch Gen Psychiatry 2000;57:471-480.
ABSTRACT | FULL TEXT  

Disturbed Gyrification of the Prefrontal Region in Male Schizophrenic Patients: A Morphometric Postmortem Study
Vogeley et al.
Am. J. Psychiatry 2000;157:34-39.
ABSTRACT | FULL TEXT  

In vivo investigation of white matter pathology in schizophrenia with magnetisation transfer imaging
Foong et al.
J. Neurol. Neurosurg. Psychiatry 2000;68:70-74.
ABSTRACT | FULL TEXT  

The neuropathology of schizophrenia: A critical review of the data and their interpretation
Harrison
Brain 1999;122:593-624.
ABSTRACT | FULL TEXT  

Compromised White Matter Tract Integrity in Schizophrenia Inferred From Diffusion Tensor Imaging
Lim et al.
Arch Gen Psychiatry 1999;56:367-374.
ABSTRACT | FULL TEXT  

Is Schizophrenia a Progressive Neurodevelopmental Disorder? Toward a Unitary Pathogenetic Mechanism
Woods
Am. J. Psychiatry 1998;155:1661-1670.
ABSTRACT | FULL TEXT  

Proton Magnetic Resonance Spectroscopic Imaging of Cortical Gray and White Matter in Schizophrenia
Lim et al.
Arch Gen Psychiatry 1998;55:346-352.
ABSTRACT | FULL TEXT  

Alzheimer Disease and Related Neurodegenerative Diseases in Elderly Patients With Schizophrenia: A Postmortem Neuropathologic Study of 100 Cases
Purohit et al.
Arch Gen Psychiatry 1998;55:205-211.
ABSTRACT | FULL TEXT  

Workshop on Schizophrenia
Barondes et al.
Proc. Natl. Acad. Sci. USA 1997;94:1612-1614.
ABSTRACT | FULL TEXT