ro-16-0154 and Panic-Disorder

Recent developments of benzodiazepine receptor imaging (123I-Iomazenil SPECT and 11C-Flumazenil PET) in neuropsychiatric disorders were reviewed. In focal epilepsy, a number of previous studies have reported a decreased benzodiazepine receptor binding in epileptic foci and greater sensitivity compared to regional cerebral blood flow imaging, especially for diagnosis of medial temporal lobe epilepsy. These findings indicate clinical validity of benzodiazepine receptor imaging in focal epilepsy and may be related to the "disinhibition mechanism" in GABA/benzodiazepine systems underlying epilepsy. In panic disorder, abnormal benzodiazepine receptor bindings are recently demonstrated in the temporal, parietal or frontal cortex. Further studies would clarify the "benzodiazepine dysfunction hypothesis" in panic disorder.

Topics: Brain; Carbon Radioisotopes; Epilepsy, Temporal Lobe; Flumazenil; Humans; Iodine Radioisotopes; Panic Disorder; Radiopharmaceuticals; Receptors, GABA-A; Reproducibility of Results; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

Alterations in benzodiazepine receptor function have long been hypothesized to play a role in anxiety. Animal models of anxiety involving exposure to chronic stress have shown a specific decrease in benzodiazepine receptor binding in frontal cortex and hippocampus. The purpose of this study was to examine benzodiazepine receptor binding patients with panic disorder and comparison subjects.. A quantitative measure related to benzodiazepine receptor binding (Distribution Volume (DV)) was obtained with single photon emission computed tomography (SPECT) imaging of [123I]iomazenil and measurement of radioligand concentration in plasma in patients with panic disorder and healthy controls. DV image data were analyzed using statistical parametric mapping (spm96).. A decrease in measures of benzodiazepine receptor binding (DV) was found in left hippocampus and precuneus in panic disorder patients relative to controls. Panic disorder patients who had a panic attack compared to patients who did not have a panic attack at the time of the scan had a decrease in benzodiazepine receptor binding in prefrontal cortex.. Findings of a decrease in left hippocampal and precuneus benzodiazepine receptor binding may be related to alterations in benzodiazepine receptor binding, or other factors including changes in GABAergic transmission or possible endogenous benzodiazepine compounds. Benzodiazepine receptor function in prefrontal cortex appears to be involved in changes in state-related panic anxiety.

Topics: Adolescent; Adult; Aged; Female; Flumazenil; GABA Modulators; Hippocampus; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Panic Disorder; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

The neuroanatomical networks involved in the initiation of panic attack and the maintenance of panic disorder are poorly understood. This study aimed to elucidate the possible abnormalities in benzodiazepine receptor uptake in the brain of patients with panic disorder. Seventeen unmedicated patients with panic disorder were investigated using 123I-iomazenil single photon emission tomography (SPET). Seventeen healthy age- and sex-matched volunteers served as controls. The SPET scan was taken 90 min after injection of tracer. Eleven of 17 patients (65%) showed an increased (> 2 S.D. higher than the mean of the controls) right-to-left ratio of benzodiazepine receptor uptake in the prefrontal cortex. Also, the mean right-to-left ratio of benzodiazepine receptor uptake in all 17 patients with panic disorder was higher than in the controls (P < 0.001). Our SPET study demonstrated focally altered benzodiazepine receptor uptake in the prefrontal cortices in patients with panic disorder. Magnetic resonance imaging indicated that the affected region was located in the right middle and inferior frontal gyri. The deterioration in information processing in the right prefrontal cortex may be implicated in the generation of panic disorder.

Topics: Female; Flumazenil; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Panic Disorder; Prefrontal Cortex; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

Single photon emission tomography (SPECT) imaging of the central benzodiazepine receptor (BZr) became possible with the newly developed ligand 123I-IOMAZENIL. The BZr binding was investigated in ten patients with panic disorder (PP) compared to ten epileptic patients (EP). Panic patients had lower IOMAZENIL uptake rates in the frontal, occipital and temporal cortex than EP indicating the involvement of the BZr complex in panic disorder.

Topics: Adult; Cerebral Ventricles; Female; Flumazenil; Frontal Lobe; Humans; Male; Occipital Lobe; Panic Disorder; Psychiatric Status Rating Scales; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon