Recently we were able to replicate the original finding of migrational disturbances
in the entorhinol cortex (ERC) of schizophrenic patients by measuring the distance
of pre-alpha cell clusters to the pial surface. In order to replicate this finding,
we performed a detailed analysis of the pre-alpha cell clusters in the ERC in post
mortem brains of 22 schizophrenic patients and 15 control subjects. Cluster position
relative to gray/white matter boundary were measured and normalized by the widths
of the gray matter. In the ERC the pre-alpha cell clusters were situated significantly
closer to the gray/white matter junction compared to normal controls (around 30 %,
F = 9.52, p = 0.004). No specific effects of sex, age or region of investigation were found.
In summary, this is another quantitative replication of pre-alpha cell cluster migrational
disturbances in schizophrenia, which are possibly linked to neurobiological abnormalities,
e.g. myeloarchitectonic changes. This supports the notion that developmental abnormalities
are a core feature of schizophrenia and that the search for candidate genes has to
include this aspect, too. However, it is very probable that vulnerability-associated
changes - as outlined here - have to be distinguished from disease-related changes.
Key words
schizophrenia - post mortem - ERC - pre-alpha cell clusters - neuronal migration -
neurodevelopment
References
- 1
Akil M, Lewis D A.
Cytoarchitecture of the entorhinal cortex in schizophrenia.
Am J Psychiatry.
1997;
154
1010-1012
- 2
Altshuler L L, Casanova M F, Goldberg T E, Kleinman J E.
The hippocampus and parahippocampus in schizophrenia, suicide, and control brain.
Arch Gen Psychiatry.
1990;
47
1029-1034
- 3
Arnold S E, Hyman B T, Van Hoesen G W, Damasio A R.
Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia.
Arch Gen Psychiatry.
1991;
48
625-632
- 4
Arnold S E, Ruscheinsky D D, Han L Y.
Further evidence of abnormal cytoarchitecture of the entorhinal cortex in schizophrenia
using spatial point pattern analyses.
Biol Psychiatry 1997;.
15;
42
639-647
- 5
Barbe M F.
Tempting fate and commitment in the developing forebrain.
Neuron.
1996;
16
1-4 [Review]
- 6
Beckmann H.
Developmental malformations in cerebral structures of schizophrenic patients.
Eur Arch Psychiatry Clin Neurosci.
1999;
249 Suppl 4
44-447
- 7
Beckmann H, Senitz D.
Developmental malformations in cerebral structures in ”endogenous psychoses”.
J Neural Transm.
2002;
109
421-431 [Review]
- 8
Bernstein H G, Krell D, Baumann B, Danos P, Falkai P, Diekmann S, Henning H, Bogerts B.
Morphometric studies of the entorhinal cortex in neuropsychiatric patients and controls:
clusters of heterotopically displaced lamina II neurons are not indicative of schizophrenia.
Schizophr Res.
1998;
33
125-132
- 9
Bogerts B, Meertz E, Schonfeldt-Bausch R.
Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of
brain volume and shrinkage.
Arch Gen Psychiatry.
1985;
42
784-791
- 10
Braak H, Zur Pigmentoarchitektonik der Großhirnrinde des M enschen.
I. Regio entorhinalis.
Zellforsch.
1972;
127
407-438
- 11
Brown R, Colter N, Corsellis J A, Crow T J, Frith C D, Jagoe R, Johnstone E C, Marsh L.
Postmortem evidence of structural brain changes in schizophrenia. Differences in brain
weight, temporal horn area, and parahippocampal gyrus compared with affective disorder.
Arch Gen Psychiatry.
1986 Jan;
43 (1)
36-42
- 12
Couillard-Despres S, Winkler J, Uyanik G, Aigner L.
Molecular mechanisms of neuronal migration disorders, quo vadis?.
Curr Mol Med.
2001;
1
677-688 [Review]
- 13
D’Arcangelo G, Nakajima K, Miyata T, Ogawa M, Mikoshiba K, Curran T.
Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody.
J Neurosci.
1997 Jan 1;
17 (1)
23-31
- 14
Falkai P, Bogerts B, Rozumek M.
Limbic pathology in schizophrenia: the entorhinal region - a morphometric study.
Biol Psychiatry.
1988;
24
515-521
- 15
Falkai P, Honer W G, David S, Bogerts B, Majtenyi C, Bayer T A.
No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study.
Neuropathol Appl Neurobiol.
1999;
25
48-53
- 16
Falkai P, Schneider-Axmann T, Honer W G.
Entorhinal cortex pre-alpha cell clusters in schizophrenia: quantitative evidence
of a developmental abnormality.
Biol Psychiatry.
2000;
47
937-943
- 17
Feng Y, Walsh C A.
Protein-protein interactions, cytoskeletal regulation and neuronal migration.
Nat Rev Neurosi.
2001;
2
408-416
- 18
Gleeson J G.
Neuronal migration disorders.
Ment Retard Dev Disabil Res.
2001;
7
167-171 [Review]
- 19
Guidotti A, Auta J, Davis J M, Di-Giorgi-Gerevini V, Dwivedi Y, Grayson D R, Impagnatiello F,
Pandey G, Pesold C, Sharma R, Uzunov D, Costa E, DiGiorgi Gerevini V.
Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia
and bipolar disorder: a postmortem brain study.
Arch Gen Psychiatry.
2000 Nov;
57 (11)
1061-1069
- 20
Guidotti A, Pesold C, Costa E.
New neurochemical markers for psychosis: a working hypothesis of their operation.
Neurochem Res.
2000 Oct;
25 (9 - 10)
1207-1218 [Review]
- 21 Harding B N. Malformations of the nervous system. In: Adams JH, Duchen LW, (eds)
Greenfild’s Neuropathology. 5th ed. New York; Oxford University Press 1992: pp. 521-638
- 22
Harrison P J.
On the neuropathology of schizophrenia and its dementia: neurodevelopmental, neurodegenerative
or both?.
Neurodegeneration.
1995;
4
1-12 [Review]
- 23
Hyde T M, Weinberger D R.
Seizures and schizophrenia.
Schizophr Bull.
1997;
23
611-622 [Review]
- 24
Jakob H, Beckmann H.
Prenatal developmental disturbances in the limbic allocortex in schizophrenics.
J Neural Transm.
1986;
65
303-326
- 25
Jakob H, Beckmann H.
Gross and histological-criteria for developmental disorders in brains of schizophenics.
J R Soc Med..
1989;
82
466-469
- 26
Krimer L S, Herman M M, Saunders R C, Boyd J C, Hyde T M, Carter J M, Kleinman J E,
Weinberger D R.
A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia.
Cereb Cortex.
1997;
7
732-739
- 27
Leventer R J, Cardoso C, Ledbetter D H, Dobyns W B.
LIS1: from cortical malformation to essential protein of cellular dynamics.
Trend Neurosci.
2001;
24
439-492
- 28
Lewis D A, Levitt P.
Schizophrenia as a disorder of neurodevelopment.
Annu Rev Neurosci.
2002;
25
409-432 [Review]
- 29
Marsh L, Suddath R L, Higgins N, Weinberger D R.
Medial temporal lobe structures in schizophrenia: relationship of size to duration
of illness.
Schizophr Res.
1994;
11
225-238
- 30
McEvilly R J, de Diaz M O, Schonemann M D, Hooshmand F, Rosenfeld M G.
Transcriptional regulation of cortical neuron migration by POU domain factors.
Science.
2002;
295
1528-1532
- 31
Mimmack M, Ryan M, Baba H, Navarro-Ruiz J, Iritani S, Faull R, McKen P, Jines P, Arai H,
Starkey M, Emson P, Bahn S.
Gene expression analysis: reproducible up-regulation of several members of the apolipoprotein
L family located in a high-susceptibility locus for schizophrenia on chromosome 22.
Proc Natl Acad Sci USA.
2002;
99
4680-4685
- 32
Ohmiya M, Fukumitsu H, Nitta A, Nomoto H, Furukawa Y, Furukawa S.
Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology
and aberrant differentiation of neurons in the postnatal cerebral cortex.
J Neurosci Res.
2001;
65
228-235
- 33
Phelps P E, Rich R, Dupuy-Davies S, Rios Y, Wong T.
Evidence for a cell-specific action of Reelin in the spinal cord.
Dev Biol.
2002;
244
180-198
- 34
Pilz D, Stoodley N, Golden J A.
Neuronal migration, cerebral cortical development, and cerebral cortical anomalies.
J Neuropath Exp Neur.
2002;
61
1-11 [Review]
- 35
Talamini L M, Koch T, Ter Horst G J, Korf J.
Methylazoxymethanol acetate-induced abnormalities in the entorhinal cortex of the
rat parallels with morfological findings in schizophrenia.
Brain Res.
1999;
789
293-306
- 36
Vogeley K, Hobson T, Schneider-Axmann T, Honer W, Bogerts B, Falkai P.
Compartemental volumetry of the superior temporal gyrus reveals sex differences schizophrenia
- a post-mortem study.
Schizophr Res.
1998 May 25;
31 (2 - 3)
83-87
- 37
Weinberger D R.
Implications of normal brain development for the pathogenesis of schizophrenia.
Arch Gen Psychiatry..
1987;
44
660-669
- 38
Weinberger D R.
From neuropathology to neurodevelopment.
Lancet 1995;.
26;
346
552-557 [Review]
- 39 Williams R S. Cerebral malformations arising in the first half of gestation. In:
Evrard PH, Minkowski A, (eds)
Developmental Neurobiology. New York; Raven Press 1989: pp. 11-20
- 40
Wright I C, Rabe-Hesketh S, Woodruff P W, David A S, Murray R M, Bullmore E T.
Meta-analysis of regional brain volumes in schizophrenia.
Am J Psychiatry.
2000;
157
16-25
Prof. Dr. med. Peter Falkai
Department of Psychiatry
University of the Saarland
Medical Center
D-66421 Homburg/Saar, Germany
Phone: (+49) 6841-162-4202
Fax: (+49) 6841-162-4270
Email: peter.falkai@uniklinik-saarland.de
