is considerable evidence to suggest that this nucleus may be
Oral Session I
Which Theory Do The Structural Brain
Changes Support?
WHOLE BRAIN ANALYSIS OF
STRUCTURAL CHANGES IN
SCHIZOPHRENIA
H. Sauer, H.-P. Volz, C. Gaser
Psyehkttric Department, University of Jena, D-07740 .lena.
Germany
In conventional approaches to detect structural cerebral
alterations regions of interest have to be predefined. In our
department, a deformation based morphometry was recently
developed (Gaser et al., 1999), which represents a whole brain
approach. MR-images of 85 schizophrenics and 75 controls
were compared. Volume reductions in brains of schizophrenics
were observed bilaterally in the thalamus, and in the superior
temporal gyrus, on the left side in the superior frontal and
precentral gyrus and the cerebellum, whereas on the right side
the middle frontal gyrus was reduced. Additionally, we analysed
the relationship between the severity of auditory hallucinations
and cerebral structure in schizophrenics and found a volume
decrease of the left Heschl gyrus and the left supramarginal
gyrus, and on the right side of the right inferior/middle
frontal gyrus.
The difference between schizophrenics and controls corrobo-
rate the cognitive dysmetria model of Andreasen et al. (1998).
To our knowledge, this is the first study to show that all critical
nodes of the network proposed are affected. The findings in
hallucinating schizophrenics support functional brain imaging
results of Dierks et al. (1999), suggesting an alteration of the
primary auditory cortex. According to our findings on the
supramarginal gyrus, however, language-relevant areas also
appear to be altered.
References
Andreasen et al.: Schizophrenia Bull 24:203 (1998).
Dierks et al.: Neuron 22:615 (1999).
Gaser et al.: Neuroimage 10:107 (1999).
THE MEDIODORSAL NUCLEUS OF THE
T H A L A M U S IN SCHIZOPHRENIA:
A POST-MORTEM STUDY
T.J. Cullen, M.A. Walker, H. Roberts, T.J. Crow,
P. Harrison, M. Esiri
Departments of Clinical Neurology ( Neuropathology) and
Ps:vchiatrv, Radcliffe Infirmary, Woodstock Road, University of
OxJord
The mediodorsal nucleus of the thalamus (MDT) contributes
the majority of thalamic input to the prefrontal cortex. There
abnormal in schizophrenia. We estimated the volume and the
total number of neurones in both the left and right MDT
initially in 11 male and 11 female schizophrenics and 18
matched control brains. Estimates of neuronal number were
made in thick Nissl sections using a three dimensional counting
box, whilst the boundaries of the nucleus were delineated using
an adjacent myelin stained section, as the precise borders are
difficult to define in Nissl sections. We have sampled the whole
of each nucleus systematically randomly, i.e. every neurone in
the nucleus has had an equal probability of being counted. We
have found no consistent differences in either volume or total
neuronal number between the MDT nuclei of the schizophrenics
and the controls.
Schizophrenic Control
Mean SD Mean SD
Volume Left 675 + 178 605 +_159
(ram3) Right 615 --220 640 ± 140
Number of Left 4.63xl0 ~' +1.36x10 ~' 4.64×10" :_+1.26x106
neurones R i g h t 4.30x106 --l.18x106 4.18×106 +0.96x100
STRUCTURAL ABNORMALITIES IN
FRONTAL, TEMPORAL A N D LIMBIC
REGIONS A N D INTERCONNECTING
WHITE MATTER TRACTS IN
SCHIZOPHRENIA
T. Sigmundsson,* J. Suckling, M. Maier,
S.C.R. Williams, E.T. Bullmore, K. G r e e n w o o d ,
R. Fukuda, M.A. Ron, B.K. Toone
*Institute of Psychiatry (King's College), De Crespigny Park,
London SE5 8AF, UK
Imaging studies of schizophrenia have repeatedly demon-
strated global abnormalities of cerebral and ventricular vol-
umes, but pathological change at more local levels of brain
organisation has not yet been so clearly characterised. Possible
reasons for this include morphometric analysis of only a few
brain regions of interest and heterogeneity of patient samples.
Methods." Dual echo magnetic resonance imaging (MRI)
data were acquired at 1.5T from 27 right-handed patients
satisfying DSM IV criteria for schizophrenia and with enduring
negative symptoms, and 27 healthy comparison subjects.
Between-group differences in grey and white matter volume
were estimated at each intracerebral voxel after registration of
the images in standard space. The relationship between clinical
symptom scores and brain structure was also examined within
the patient group.
Results. We found significant deficits of grey matter volume
in the patient group at three main locations: (i) left superior
temporal gyrus and insular cortex; (ii) left medial temporal
lobe including the parahippocampal gyrus and hippocampus;
and (iii) the anterior cingulate and medial frontal gyri. White
matter deficits were found in similar locations in the left
temporal lobe, extending into the left frontal lobe. The patient
group showed a relative excess of grey matter volume in the
basal ganglia. Within the patient group, basal ganglia grey
matter volume was positively correlated with positive symp-
tom scores.
Conclusion. These data are compatible with models of schizo-
phrenia as a supraregional disorder of multiple, distributed
brain regions and the axonal connections between them.
RIGHT FRONTAL HYPERGYRIA
DIFFERENTIATES AFFECTED FROM
HEALTHY SIBLINGS IN FAMILIES WITH
SCHIZOPHRENIA
K. Vogeley, R. Tepest, U. Pfeiffer, P. Falkai
Address for correspondence. Dr. Kai Vogeley, Department o[
Psychiatry, Sigmund-Freud-Str. 25, 53105 Bonn. FRG,
Phone: 0044 228 287 6122, Fax: 0044 228 287 5025.
e-maiL" vogelev@uni-bonn.de
The macroscopic development of the frontal lobe including
its gyrification is mostly completed during fetal life, therefore,
its examination provides considerable information on early
brain development. The measurement of the gyrification index
(GI) as ratio of inner and outer contour (Zilles et al. 1988)
revealed a right frontal hypergyria in male schizophrenics in a
post mortem sample (Vogeley et al., in press). To further
evaluate the significance of this finding, the gyrification index
was now measured in 13 age- and gender-matched pairs from
families with schizophrenia with one affected and one non-
affected sibling. Measurements were performed on standard 1,5
Tesla Tl-weighted MRI images on three subsequent slices
starting at the anterior border of the corpus callosum (10mm
distance). Outer and inner gyral contour were traced manually,
image analysis was performed with Optimas6.0 (Window95).
Mean GI values revealed a significant right frontal hypergyria
in schizophrenia. There were no gender differences in GI
measurements in this sample. This study corroborates previous
findings in a post mortem sample. It is proposed that the
hypergyria is a developmental marker in schizophrenia.
References
Vogeley K., Schneider-Axmann T., Pfeiffer U., Tepest R., Bayer
T.A., Bogerts B., Honer W.G., Falkai P. Disturbed gyrification
of the prefrontal region in male schizophrenics - - a morpho-
metric post mortem study. Am J. Psychiatry (in press).
Zilles K., Armstrong E., Schleicher A., Kretschmann H.J. The
human pattern of gyrification in the cerebral cortex. Anat
Embryol, 1988, 179, 174-179.
Supported by the Stanley Foundation and the DFG
( Fa 241/2-2).
PRENATAL EXPOSURE TO FAMINE AND
BRAIN MORPHOLOGY IN
SCHIZOPHRENIA
H.E. H u l s h o f f P o l , H.W. Hock, E. Susser, A.S. Brown,
A. Dingemans, H.G. Schnack, N.E.M. v a n Haren,
L.M.P. R a m o s , C.C. Gispen-de Wied, R.S. K a h n
Department of Psychiatry, University Medical Center Utrecht,
AO1.126. Heidelberglaan 100, 3584 CX, The Netherlands
Background." A twofold increased incidence of schizophrenia
was found in a birth cohort exposed to the Dutch Hunger
Winter at the end of World War II during the first trimester of
gestation (Susser et al., 1996). However, it is not known
whether pre-natal nutritional deficiency contributes to struc-
tural brain abnormalities in schizophrenia.
Methods: Nine schizophrenic patients and 9 healthy controls
from the birth cohort, and 9 non-exposed schizophrenic patients
and 9 non-exposed healthy controls were evaluated with 1.5T
magnetic resonance brain imaging.
Results. An interaction effect of schizophrenia with hun-
gerwinter for intracranial volume was found (F(1.32)=6.52,
p = 0.02). Prenatal famine exposure in schizophrenia was associ-
ated with decreased intracranial volume. Hungerwinter expo-
sure alone was related to an increase in brain abnormalities - -
predominantly white matter hyperintensities (Fisher's exact,
p=0.04). No effects on total brain, gray and white matter,
cerebellar, lateral and third ventricular volumes were found.
Conclusions." Nutritional deficiency in the first trimester of
gestation resulted in an increase in clinical brain abnormalities
and was associated with abberant early brain development in
patients with schizophrenia. Stunted brain development second-
ary to factors affecting brain growth in the first trimester of
gestation may thus be a potential risk factor for developing
schizophrenia.
Acknowledgement. This research was supported by the
Theodore & Vada Stanley Foundation.
REDUCED LEFT ANTERIOR
CINGULATE/PARACINGULATE
FISSURIZATION IN MALES WITH FIRST-
EPISODE PSYCHOSES BUT NOT FEMALES:
A MRI MORPHOMETRIC STUDY
M. Yucel, D. Velakoulis, P. Maruff, G.W. Stuart,
D.J. Smith, G. Savage, S. Crowe, W.J. Brewer,
T. Profitt, K. M a h o n y , L. Leeton, C. Pantelis
Cognitive NeuropaTchiatry Unit, The Mental Health Research
Institute of Vietoria, Locked Bag 11, Parkville, VIC3052,
Australia
Recent brain imaging work has revealed normal anatomical
asymmetries that are absent or reversed in patients with psycho-
sis. Our previous work in control subjects has found an