ro-16-0154 and Anxiety-Disorders

123I-Iomazenil (123I-IMZ) and 123I-IMP imaging were performed in 5 patients with anxiety disorder (PAD) and 6 normal volunteers (NV). On 123I-IMZ delayed imaging, the 2 PAD showed abnormally decreased findings. In anxiety disorder, decreased accumulation on 123I-IMZ delayed images was seen in left hippocampus and parahippocampal gyrus in one patient, in right frontal and temporal lobe and left occipital pole in the other. Compared with NV, PAD had lower 123I-IMZ uptake on delayed image in right upper and left lower frontal cortices, indicating the involvement of the benzodiazepine receptor complex in anxiety disorder. Compared with grading for anxiety disorder with Hamilton anxiety scale (HAS) and delayed to early count ratios of 123I-IMZ, negative correlation (R < -0.7) was recognized hippocampus and parahippocampal gyrus, frontal and occipital cortices. Compared between HAS and the count ratio to the cerebellum on 123I-IMP image, positive correlation (R > 0.7) was recognized in the hippocampus, the parahippocampal gyrus, the lower outer temporal cortex and the lower frontal cortex.

Topics: Amphetamines; Anxiety Disorders; Brain; Cerebrovascular Circulation; Female; Flumazenil; Humans; Iodine Radioisotopes; Iofetamine; Male; Middle Aged; Perfusion; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

In this report, we describe the case of a caucasian male patient, aged 42 years, suffering from severe treatment-resistant generalized anxiety disorder with panic attacks and from severe major depression, for which he was treated with a course of electroconvulsive therapy. During electroconvulsive treatment, anesthesia was difficult to induce with etomidate and, once, propofol. Bispectral indices recordings (assessing the depth of anesthesia) revealed a much shorter duration of loss of responsiveness compared to a control patient receiving also a course of electroconvulsive therapy. Since GABA receptor-mediated regulation of cortical excitability is important with respect to general anesthesia, we investigated the density of GABA(A) receptors with (123)I-iomazenil SPECT and found a clearly diminished binding of the radiotracer in the right frontal and orbitotemporal regions compared to the recordings in a 38-year-old healthy male control. Genetic analysis of the exons 7 and 8 of the GABRB1-3 genes coding for the beta1-3 subunits of the GABA(A) receptors revealed a silent G to A substitution in the third position of amino acid 257 of the beta1-subunit. To our knowledge, this is the first report of a link between insensitivity to anesthetic agents and altered GABA(A) receptor function in a clinical case. Whereas reduced GABA(A) receptor-binding capacity has been investigated in anxiety disorders, this has not been the case in depressive disorders. This case illustrates how clinical observations in psychiatry can prompt investigation by modern techniques and potentially link clinics and basic sciences. No conclusion can, however, be made about casual links in this single case [corrected].

Topics: Adult; Anxiety Disorders; Binding Sites; Brain Mapping; Cerebral Cortex; Depression; Electroconvulsive Therapy; Etomidate; Exons; Flumazenil; Gene Silencing; Humans; Hypnotics and Sedatives; Iodine Isotopes; Male; Point Mutation; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Brain; Female; Flumazenil; Humans; Iodine Radioisotopes; Mental Disorders; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Effects of repeated swim stress on the binding of 125I-iomazenil were examined in the brains of diazepam-treated and non-treated mice. The mice were orally administered diazepam or vehicle (0.5% ethylene glycol) and subjected to daily swim stress (at 20 degrees C for 10 min) for seven consecutive days. The distribution and the amount of 125I-iomazenil binding were analyzed autoradiographically after in vivo and in vitro binding experiments. Repeated swim stress decreased the in vivo binding in the hippocampus (p < 0.05) and cerebral cortex (p < 0.05) of vehicle-treated mice but caused no significant changes in diazepam-treated mice. Subchronic treatment with diazepam decreased the in vivo binding approximately 50% in all brain regions examined (p < 0.01). The in vitro experiment, however, revealed no significant changes except in the hippocampus, where a small but significant decrease in the binding was observed after subchronic treatment with diazepam (p < 0.01). The stress- or diazepam-induced reductions seem to represent alterations in the in vivo environment related to 125I-iomazenil binding. These results suggest that we can investigate the pathophysiology of stress and anxiety with 123I-iomazenil SPECT. Care must be taken concerning the effects of benzodiazepines.

Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Autoradiography; Brain; Diazepam; Flumazenil; Iodine Radioisotopes; Male; Mice; Mice, Inbred ICR; Stress, Physiological; Tomography, Emission-Computed, Single-Photon

The purpose of this study is visual evaluation of the distribution of I-123 iomazenil in the brains of patients with various types of mental disorder and to examine whether chronic administration of a clinical dose of benzodiazepine (BZ) affects the binding of I-123 iomazenil to BZ receptors (BZR). The subjects were 10 patients with mental disorders (3 males and 7 females) with a mean age of 26.8 yrs (range 19-39 yrs). Four of 10 patients were administered BZ for over 3 months and the other six were free of BZ for over one month. The SPECT images were obtained at 5-25 min (early) and 170-190 min (delayed), after the bolus i.v. injection of 167 MBq of I-123 iomazenil, with a triple-head gamma camera. The images were visually evaluated and the washout ratios of each region were calculated. In visual analysis, abnormalities were recognized in 5 patients on the delaye SPECT. The abnormalities were recognized more frequently in the superior frontal lobe. The washout ratio was higher in the BZ (+) patient group than in the BZ (-) patient group. I-123 iomazenil is useful, because the SPECT image with I-123 iomazenil reflects the distribution of BZR on the brain and provides the different information from that obtained with perfusion SPECT, X-ray CT or MRI. The rapid washout of I-123 iomazenil from the brains of BZ (+) patients suggests that chronic administration of a clinical dose of BZ affects the binding of I-123 iomazenil to BZR.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Brain; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Mental Disorders; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon