Am J Psychiatry 1997; 154:56-63
Copyright © 1997 by American Psychiatric Association
Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia [published erratum appears in Am J Psychiatry 1997 May;154(5):722]
GF Busatto, LS Pilowsky, DC Costa, PJ Ell, AS David, JV Lucey and RW Kerwin
Department of Psychological Medicine, Institute of Psychiatry, London, U.K.
OBJECTIVE: Although there is evidence from postmortem studies suggestive of
deficient inhibitory neurotransmission of gamma- aminobutyric acid (GABA)
in schizophrenia, no direct in vivo evidence has been obtained to date. The
authors used single photon emission computed tomography (SPECT) with
iodine-123-labeled iomazenil ([123I]iomazenil), a radioligand that
selectively binds with high affinity to the benzodiazepine subunit of the
GABAA receptor complex in the human brain, to investigate the presence of
benzodiazepine receptor abnormalities in the cerebral cortex of living
subjects with schizophrenia. METHOD: Dynamic [123I]iomazenil SPECT was
performed in 15 patients (14 patients with DSM-III-R schizophrenia and one
with schizophreniform disorder) and 12 healthy subjects over a period of 2
hours. The time-integral method was used to generate ratios of "specific"
to "nonspecific" [123I]iomazenil binding at equilibrium for several
cortical regions. RESULTS: No overall between-group differences in
benzodiazepine receptor binding were found, but significant correlations
emerged between the severity of schizophrenic symptoms and [123I]iomazenil
binding in limbic cortical regions: positive symptom scores were negatively
correlated with benzodiazepine receptor binding in the left medial temporal
region, and negative symptoms were inversely related to receptor binding in
the medial frontal region. These correlations were not significant when a
Bonferroni correction for multiple comparisons was applied. CONCLUSIONS:
These preliminary results are consistent with previous research implicating
limbic cortical regions in the pathophysiology of schizophrenia, suggesting
that reduced inhibitory GABAergic tone in these areas may contribute to the
appearance of schizophrenic symptoms.
