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]

• Published in: The American journal of psychiatry Vol. 154; no. 1; pp. 56 - 63
• Main Authors: BUSATTO, G. F, PILOWSKY, L. S, COSTA, D. C, ELL, P. J, DAVID, A. S, LUCEY, J. V, KERWIN, R. W
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01-01-1997; American Psychiatric Association
• Subjects: Acids; Adolescent; Adult; Adult and adolescent clinical studies; Antipsychotics; Benzodiazepines; Biological and medical sciences; Brain; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - metabolism; Dopamine; Female; Flumazenil - analogs & derivatives; Frontal Lobe - diagnostic imaging; Frontal Lobe - metabolism; gamma-Aminobutyric Acid - physiology; Humans; Hypotheses; Iodine; Male; Medical sciences; Patients; Psychiatric Status Rating Scales; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Psychosis; Psychotropic drugs; Receptors, GABA-A - metabolism; Schizophrenia; Schizophrenia - diagnosis; Schizophrenia - diagnostic imaging; Schizophrenia - physiopathology; Schizophrenic Psychology; Severity of Illness Index; Temporal Lobe - diagnostic imaging; Temporal Lobe - metabolism; Tomography; Tomography, Emission-Computed, Single-Photon; Human; Psychosis; In vivo; Symptomatology; Cerebral cortex; Pathophysiology; Central nervous system; Schizophrenia; Benzodiazepine receptor; Brain (vertebrata)
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/ajp.154.1.56

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.