Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia.
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.


METHODS
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.
Busatto
G F
GF
Department of Psychological Medicine, Institute of Psychiatry, London, U.K.
Pilowsky
L S
LS
Costa
D C
DC
Ell
P J
PJ
David
A S
AS
Lucey
J V
JV
Kerwin
R W
RW
D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011963:Receptors, GABA-A / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C063038:iomazenil