ro-16-0154 and Depressive-Disorder--Major

A recent magnetic resonance spectroscopy (MRS) study revealed low gamma-aminobutyric acid (GABA) levels in the occipital cortex of depressed patients. No in vivo study has been reported to measure postsynaptic GABA receptors in the patients.. Cortical benzodiazepine (BZ) binding to GABA(A) receptors was measured with [(123)I]iomazenil and single photon emission computed tomography in unmedicated patients with unipolar major depression (n = 13) and healthy subjects (n = 19). Group differences were evaluated by means of statistical parametric mapping (SPM) with partial volume correction for gray matter. Occipital GABA levels were determined by proton MRS in a subgroup (n = 6) of the patients.. No evidence of altered BZ binding was found in patients with depression compared with healthy control subjects in the SPM analysis. Although reduction in gray matter volume was observed in the frontal cortex and amygdala of the patients, partial volume correction of the atrophy did not change the result of unaltered BZ binding. GABA levels were found lower in the occipital cortex; however, BZ binding did not show significant relationship to GABA levels.. GABA(A) receptor binding measured in vivo with BZ radioligand binding are not altered in patients with depression.

Topics: Adult; Binding Sites; Brain; Depressive Disorder, Major; Female; Flumazenil; gamma-Aminobutyric Acid; Humans; Male; Occipital Lobe; Receptors, GABA; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT.. Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT.. An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices.. Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.

Topics: Adult; Brain; Cerebral Cortex; Depressive Disorder, Major; Dominance, Cerebral; Electroconvulsive Therapy; Female; Flumazenil; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuropsychological Tests; Radioligand Assay; Receptors, GABA-A; Regional Blood Flow; Synaptic Transmission; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Treatment Outcome