Based on preclinical evidence that the GABA-benzodiazepine (Bz) complex might play a role in pathologic states of anxiety, our original study examined sensitivity to successive injections of IV diazepam in panic disorder patients and controls, using saccadic eye velocity as the major pharmacodynamic measure. In our initial sample, we found reduced Bz effects on saccadic velocity, as well as sedation and memory, in panic disorder patients. Because of less robust panic-control differences in a larger sample of panic patients, intermediate Bz sensitivity values found in a smaller group of generalized anxiety disorder patients and the absence of testing in additional groups of anxious patients, the clinical and diagnostic specificity of this finding is unclear. In addition, because panic patients also showed reduced sedative effects following diazepam, it is possible that differences in saccadic velocity effects are a nonspecific manifestation of differences in arousal between patients and controls rather than a reflection of differences in GABA-Bz complex functioning in brainstem areas controlling saccadic eye velocity. This study will test the diagnostic, clinical and physiologic specificity of reduced Bz sensitivity by employing three major strategies. First, panic patients and controls will be compared to two additional groups of anxious patients (obsessive-compulsive disorder and social phobia). Second, an expanded range of clinical measures will be included to explore clinical correlates of Bz sensitivity across patient groups. Finally, to begin to clarify the physiologic meaning of reduced Bz sensitivity, injections of TRH will be used in panic patients and controls to attenuate the sedative effects of Bzs. Since TRH does not affect Bz-induced saccadic slowing, this intervention will be used to test the hypotheses that panic-control differences in Bz sensitivity (i.e., saccadic slowing) are independent of Bz-induced sedation and persist after TRH has blocked panic-control differences in sedation.
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