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a Division of
Neuroscience and Psychological Medicine, Imperial College School of
Medicine, Charing Cross Hospital, London, U K, b Department of Anatomy, National University
of Singapore, Singapore, c Department of
Psychiatry, University of Hull, Hull, U K
Correspondence to: Professor L J Garey, Division of Neuroscience, Imperial College School of Medicine, Charing Cross Hospital, London W6 8RF, UK. Telephone 0044 181 846 7036; fax 0044 181 846 7025; e-mail: l.garey{at}ic.ac.uk
Received 20
March 1997 and in revised form 18 June 1998;
Accepted 29 June
1998
OBJECTIVE
A pilot study of the density of
dendritic spines on pyramidal neurons in layer III of human temporal
and frontal cerebral neocortex in schizophrenia.
METHODSPostmortem material from a group
of eight prospectively diagnosed schizophrenic patients,
five archive schizophrenic patients, 11 non-schizophrenic controls,
and one patient with schizophrenia-like psychosis, thought to be due to
substance misuse, was impregnated with a rapid Golgi method. Spines
were counted on the dendrites of pyramidal neurons in temporal
and frontal association areas, of which the soma was in layer III
(which take part in corticocortical connectivity) and which met strict
criteria for impregnation quality. Altogether 25 blocks were studied in
the schizophrenic group and 21 in the controls. If more than one block
was examined from a single area, the counts for that area were
averaged. All measurements were made blind: diagnoses were only
disclosed by a third party after measurements were completed. Possible
confounding affects of coexisiting Alzheimer's disease were taken into
account, as were the effects of age at death and postmortem interval.
RESULTSThere was a significant (p<0.001)
reduction in the numerical density of spines in schizophrenia (276/mm
in control temporal cortex and 112/mm in schizophrenic patients, and
299 and 101 respectively in the frontal cortex). An analysis of
variance, taking out effects of age at death and postmortem interval,
which might have explained the low spine density for some of the
schizophrenic patients, did not affect the significance of the results.
CONCLUSIONThe results support the
concept of there being a defect in the fine structure of dendrites
of pyramidal neurons, involving loss of spines, in schizophrenia
and may help to explain the loss of cortical volume without loss of
neurons in this condition, although the effect of neuroleptic drugs
cannot be ruled out.
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