Файл: An.Atlas.of.Schizophrenia.eBook-EEn.pdf

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©2002 CRC Press LLC

Figure 3.2 

Mean ventricle : brain ratio (VBR)

in controls and patients with schizophrenia
from a total of 39 separate studies. The
diagonal line indicates the line of equality.
Thus, this figure demonstrates that no matter
which diagnostic system or method of
measuring brain volume is used, patients
with schizophrenia do have larger ventricles
than controls. Figure reproduced with
permission from Van Horn JD, McManus IC.
Ventricular enlargement in schizophrenia. A
meta-analysis of studies of the ventricle :
brain ration (VBR). 

Br J Psychiatry

1992;160:687–97

12

2

4

6

8

10

10

0

Schizoph

renic mean VBR

12

Control mean VBR

8

6

4

2

0

DSM–III

RDC

DSM–III/RDC

WUC

DSM–III

RDC

DSM–III/RDC

Line of equality

Diagnostic criteria and methods of measurement:

INCREASED VENTRICLE VOLUME  

IN SCHIZOPHRENIA

Planimetry  

            Computerized

Figure 3.3  

Ventricular size in monozygotic twins discordant for schizophrenia. Coronal magnetic resonance images

of twins discordant for schizophrenia show lateral ventricular enlargement in the affected twin. Figure reproduced with
permission from Suddath RL, Christison GW, Torrey EF, 

et al

. Anatomical abnormalities in the brains of monozygotic

twins discordant for schizophrenia. 

N Engl J Med

1990;322:789–4


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©2002 CRC Press LLC

Figure 3.4

Meta-analysis of absolute regional brain volumes in schizophrenic patients and controls, from a total of 58 studies.

This figure shows how the mean volumes of different brain regions from people with schizophrenia differ from those of
controls. Figure reproduced with permission from Wright IC, Rabe-Hesketh S, Woodruff PW, 

et al

. Meta-analysis of regional

brain volumes in schizophrenia. 

Am J Psychiatry 

2000;157:16–25

Ventricular structures

Left lateral ventricle

Right lateral ventricle

Left frontal horn

Right frontal horn

Left body ventricle

Right body ventricle

Left occipital horn

Right occipital horn

Left temporal horn

Right temporal horn

Third ventricle

Fourth ventricle

Total ventricles

Cortical/limbic structures

Left hemisphere

Right hemisphere

Left frontal volume

Right frontal volume

Left temporal lobe

Right temporal lobe

Left amygdala

Right amygdala

Left hippocampus-amygdala

Right hippocampus-amygdala

Left hippocampus

Right hippocampus

Left parahippocampus

Right parahippocampus

Left superior temporal gyrus

Right superior temporal gyrus

Left anterior superior temporal gyrus

Right anterior superior temporal gyrus
Left posterior superior temporal gyrus

Right posterior superior temporal gyrus

Whole brain

Subcortical structures

Left caudate

Right caudate

Left putamen

Right putamen

Left globus pallidus

Right globus pallidus

Left thalamus

Right thalamus

Whole brain gray/white matter

Gray matter

White matter

Comparative mean volume of subjects with schizophrenia (%)

80 100 120

90 110 

130 140 150 160 170

180

COMPARATIVE MEAN VOLUMES OF BRAIN REGIONS IN SCHIZOPHRENIA


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©2002 CRC Press LLC

hamartomas and arteriovenous malformations
occur with increased frequency in schizophrenia.

At the cellular level, various abnormalities in

cytoarchitecture have been reported in several
brain regions, although not all of these findings
have proved robust. However, evidence of
neuronal displacement (

Figure 3.7

) suggests the

possibility of some failure in neuronal migration, a
process that occurs mainly during the second
trimester of fetal development

4

.

Several findings weigh against the most likely

alternative of a neurodegenerative process. The
balance of evidence is that most of the brain

abnormalities seen in schizophrenia are present at
first onset and are non-progressive. Furthermore,
markers of neurodegeneration, such as proteins
associated with glial response are largely absent,
although there may be a small degree of
periventricular gliosis. Extracerebral markers of
abnormal fetal development provide indirect
support for the idea that aberrant neurodevelop-
ment is implicated in schizophrenia. Dermato-
glyphic abnormalities are thought to reflect fetal
maldevelopment and appear to be more common
in schizophrenia (

Figure 3.8

). Minor physical

anomalies also occur with greater frequency in

Figure 3.5 

Some structural brain abnormalities possibly implicated in the pathogenesis of schizophrenia. Structural

abnormalities have been described in many brain areas, and at a variety of anatomical levels, from gross macroscopic
changes in whole brain volume, through to subtle cellular displacement or disorganization in the cortex. Increasingly, interest
has focused on the distribution of abnormalities, and their structural connectivity: thus, white matter myelination, as well as
cortical abnormalities, are targets of investigation

Enlarged lateral

ventricles

Abnormalities

of white matter

Reduced hippocampal

volume

Reduced brain
volume

Gyral
abnormalities

Cortical cellular
displacement

Blunted temporal horns

of lateral ventricles

STRUCTURAL BRAIN ABNORMALITIES IN SCHIZOPHRENIA


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©2002 CRC Press LLC

schizophrenic patients compared with normal
controls.

FUNCTIONAL BRAIN IMAGING

Functional brain imaging studies have used
positron emission tomography (PET), single
photon emission tomography (SPET) and, more
recently, functional magnetic resonance imaging
techniques (fMRI) to investigate regional cerebral
blood flow (rCBF) and brain metabolism in
schizophrenia (

Figure 3.9

)

5

.

It was previously thought that a decrease in

frontal blood flow and metabolism (‘hypofronta-
lity’) was a constant feature of schizophrenia.
However, this now appears to be a function of the
cognitive load involved in the test that patients are
carrying out at the time. For example, activation
studies using ‘frontal’ tasks such as the Wisconsin

card sorting test have shown that healthy
volunteers increase blood flow to the dorsolateral
prefrontal cortex during the task, while this is not
apparent when schizophrenic patients perform
the task. Other studies using verbal fluency as an
activation task have found impaired frontal blood
flow in schizophrenic patients (

Figure 3.10

)

6

.

However, there are studies on both tasks that have

Figure 3.6 

Agenesis of the corpus callosum. This midline

sagittal magnetic resonance image shows an absent corpus
callosum, a dramatic example of a neurodevelopmental
anomaly which, while extremely rare, is thought to have an
increased incidence in people with schizophrenia

Figure 3.7 

These camera lucida drawings compare the

distribution of nicotinamide-adenine dinucleotide
phosphate-diaphorase-stained neurons (squares) in sections
through the superior frontal gyrus of a control and
schizophrenic brain. There is a significant shift in the
direction of the white matter in the schizophrenic brain.
Numbers 1 through 8 indicate compartments of the brain;
Roman numerals indicate cortical layers. Figure
reproduced with permission from Akbarian S, Bunney WE,
Jr, Potkin SG, 

et al.

Altered distribution of nicotinamide-

adenine dinucleotide phosphate-diaphorase cells in frontal
lobe of schizophrenics implies disturbances of cortical
development. 

Arch Gen Psychiatry

1993:50:169–77

3

2

1

4

5

6

7

8

Controls Schizophrenics

I

II

III

I

II

III

IV

IV

V

V

VI

VI


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©2002 CRC Press LLC

Figure 3.9

Oxyhemoglobin and deoxyhemoglobin have slightly different magnetic properties, and this is used as the basis

for the blood oxygenated level dependent (BOLD) method in functional magnetic resonance imaging (MRI). Increases in
neuronal activity are accompanied by increases in regional cerebral blood flow, which exceed the increase in cerebral
oxygen utilization. As a result the oxygen content of the venous blood is increased, leading to an increase in MRI signal
intensity. Figure reproduced with permission from Longworth C, Honey G, Sharma T. Science, medicine, and the future.
Functional magnetic resonance imaging in neuropsychiatry. 

Br Med J 

1999;319:1551–4

BASIS OF FUNCTIONAL MAGNETIC RESONANCE IMAGING

Change in blood oxygenation

D

Increased local cerebral blood flow

Neuronal activity

Figure 3.8 

Structural abnormalities may be found in

schizophrenia outside the CNS; other structures that
develop at the same time may also be involved. In
monozygotic twins there should be little or no
difference between the twins in total finger ridge
count. It can be seen, however, that in twin pairs
where one twin suffers from schizophrenia, there is a
much greater difference in total finger ridge count.
This is significant because finger ridges develop in the
second trimester and therefore the differences
illustrated in this slide may indicate a degree of
maldevelopment in affected twins

60

10

20

30

40

50

0

Absolute intrapair diffe

rence  

in total ridge count

Monozygotic twin pairs

Nonschizophrenic

(n = 7)

Discordant for

schizophrenia

(

n

 = 23)

Pair discordant for depression

DERMATOGLYPHIC ABNORMALITIES 

IN SCHIZOPHRENIA