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B RIIT I S H J OU RN AL OF P SYCH IAT RY (2003), 1 83, 414
Size of hippocampal pyramidal neurons
in schizophrenia
J. R. HIGHLEY, M. A. WALKER, B. McDONALD, T. J. CROW and M. M. ESIRI
Background Meta-analyses of
hippocampal size have indicated that this
structure is smaller in schizophrenia.This
could reflect a reduction in the size of
constituent neurons or a reduced number
of neurons.
Aims To measure the size of
hippocampal pyramidal neurons in the
brains of people with and without
schizophrenia.
Method Pyramidal neuron size in
hippocampal subfields was estimated
stereologically from sections taken at
5 mm intervals throughout the whole
length of right and left hippocampi from
the brains of 13 people with schizophrenia
and 16 controls. Results were assessed
using repeated-measures analysis of
covariance looking for a main effect of
diagnosis and gender, and interactions of
these with side.
Results We were unable to detect
significant differences related to diagnosis,
gender or side for any hippocampal
subfield for this series of cases.
Conclusions For this series of brains,
hippocampal cell size is unchanged in
schizophrenia.
Declaration of interest None.
Funding detailed in Acknowledgements.
The hippocampus has interested investiga-
tors into schizophrenia for many decades.
Experimental and human studies have
shown its undoubted importance for mem-
ory function, which is selectively impaired
in people with schizophrenia (Gruzelier et
al, 1988; Saykin et al, 1991; Gur et al,
1998). Furthermore, some structural ima-
ging studies of living patients, as well as
post-mortem studies, report reductions in
hippocampal size in schizophrenia (Bogerts
et al, 1985; Falkai & Bogerts, 1986; Jeste
& Lohr, 1989; Nelson et al, 1998)-
although not all studies confirm this, per-
haps because the numbers of individuals
studied were sometimes too low to detect
the quite subtle reductions described (Alt-
shuler et al, 1990; Bruton et al, 1990;
Heckers et al, 1990, 1991). The meta-
analysis of in vivo magnetic resonance ima-
ging (MRI) studies by Nelson et al (1998)
indicated a reduction in hippocampal size
of approximately 4%.
Reduction in size of a brain structure
may reflect a reduced size of the constituent
glial cells and neurons and their processes
as well as (or as an alternative to) a reduced
number of neurons. Thus, it is important to
document estimates of cell size as well as
cell number in brain structures that are of
interest in schizophrenia. Here we present
our findings with respect to pyramidal cell
volume, estimated stereologically, in the
hippocampus on both sides of brains taken
from 13 people with schizophrenia and 16
controls.
METHOD
The brains studied in this investigation
were a subset of 29 samples from a collec-
tion that has been described elsewhere
(Highley et al, 1999; McDonald et al,
2000; Walker et al, 2002). In brief, brains
were collected post mortem from patients
with schizophrenia and a control group,
and fixed by suspension in 10% formalin
solution. The case notes of the patients
and controls were assessed by a psychiatrist
(T.J.C. or Dr Stephen J. Cooper from
Queen’s University, Belfast) to ensure that
they either fulfilled DSM-IV criteria for
schizophrenia or schizoaffective disorder
(American Psychiatric Association, 1994),
or were free of psychopathological dis-
order. The next of kin gave consent for
use of brain tissue for research. All brains
were examined by a neuropathologist
(B.M.), masked to diagnosis and gender,
who confirmed them as being free from
significant neuropathological changes. In
particular, there was no evidence of
cerebrovascular disease, Alzheimer’s dis-
ease or Parkinson’s disease. All measures
were made (by M.A.W.) masked to diag-
nosis and gender. The demographic details
of the brain donors in this study are given
in Table 1.
The temporal lobes were dissected
away from the rest of the brain, and sliced
into 5 mm coronal slices throughout their
entire length, such that the entirety of the
hippocampus was available for histological
examination. Each slice was embedded in
paraffin wax, and a 25 mm section was
cut from its anterior face, mounted on a
coated slide, stained with cresyl violet
and luxol fast blue, and coverslipped.
The outlines of four cytoarchitecturally
defined hippocampal subfields were delin-
eated in the manner described by West &
Gundersen (1990):
(a) the hilus (CA4)
(b) an amalgamation of the CA2 and CA3
subfields (hereafter CA2/3)
(c) the CA1 subfield
(d) the subiculum.
The volume density (Vv) of these subfields
was measured on both sides of the brain,
using stereological point-counting tech-
niques (Howard & Reed, 1998). Volume
density in this study refers to the proportion
of each hippocampal subfield that is
occupied by pyramidal neuronal cell
bodies.
The prepared slides were examined
using a 660 objective and an Olympus
BX50 microscope mounted with a JVC
TK-C1380 colour video camera and stage
motor, which in turn were controlled and
viewed on a computer running the Olym-
pus Cast-Grid 2.0 stereology sampling soft-
ware. On each slide, each subfield was
examined at specific points positioned in a
raster search pattern array which covered
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