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Growth hormone response to oral yohimbine in panic disorder patients versus controls
BIOL PSYCHIATRY 1991 ;29:43A-185A
54A
25
Growth Hormone Secretion
GROWTH HORMONE RESPONSE TO ORAL YOHIMBINE IN PANIC DISORDER PATIENTS VERSUS CONTROLS Thomas W. Uhde, M.D., George Gurguis, M.D. National Institute of Mental Health, Bethesda, MD 20892. Panic disorder patients have blunted (growth hormone) GH responses to clonidine and to GRH relative to normal controls, indicating possible abnormalities in the noradrenergic control of GH release. We investigated the behavioral, neuroendocrine, and biochemical effects of oral yohimbine (20 rag) or placebo in I 1 panic disorder patients and 7 normal controls. Behavioral ratings and biological samples were obtained at baseline and at hourly intervals (up to 5 hr) after drug administration. There were no significant baseline differences between patients and controls in baseline levels of GH. No significant Group x Time interaction on ratings of anxiety or GH were noted after placebo. Yohimbine produced a significant main effect increase on ratings of anxiety, although the panic disorder patients had a greater anxiogemc response compared to normal controls. A transient but significant increase in GH levels occurred + 60 min after yohimbine. Panic patients had blunted l-hr GH responses compared to controls. There were no differences in peak GH levels between patients (n = 6) who panicked compared to ~ose who did not panic (n = 6) after yohimbine. Our observations suggest that panicogcnic doses of yohimbine may he associated with brief but significant increases in growth hormone. Blunted GH responses to yohimbine may represent further evidence of a hyporesponsive hypothalamic--GH system in panic disorder. Assuming that yohimbine completely blocks postsynaptic or-2 receptors in the hypothalamus, our data indicate that some anxiety states, even those induced by yohimbine, may be associated with increases in GH via mechanisms independent of ¢t-2 adrenergic receptors.
26
NON-LINEAR MULTIOSCILLATOR ANALYSES OF NORADRENERGIC AND NEUROENDOCRINE REGULATION IN DEPRESSION Robert L. Trestman, Ph.D., M.D., Martin H. Teicher, M.D., Ph.D., Emil F. Coccaro, M.D., David Harper, B.S., Vivian Mitropoulou, M.A., Steven Gabriel, Ph.D., Peter Knott, Ph.D., Larry J. Siever, M.D. Mt. Sinai School of Medicine~Bronx VAMC, New York, IVY 10029. The hypothesis of dysregulated monoamine/neuroendocrme systems in major depression implies that, compared to normal controls, i) the relative amplitude of circadian alterations in plasma metaboiites of these systems will be reduced or flattened, 2) the phase relationships among the monoamine/neumendocrine systems will be disturbed, and 3) normally dominant circadian rhythms will be replaced with higher frequency ultradian harmonics. Non-linear multioscillator cosinor analysis of serial plasma metabolite concentrations is a tool that allows these questions to be addressed. Concentrations of plasma MI-IPG were sampled hourly and plasma norepinep,hrine, cortisol, growth hormone, and prolactin were sampled at half hour intervals over 24 hr in 16 patients with acute major depression and 12 normal controls. Preliminary findings in a subsample of 13 acutely depressed patients and 6 normal controls revealed a decrease in circadian (p < 0.05) and a trend toward a decrease in ultradian (p < 0.1) relative amplitudes of plasma cortisoi, a phase advance of plasma MHPG (p < 0.05), and increased variability in MHPG rhythms in acutely depressed patients compared to normal controls. These results support the utility of the multioscillator model and offer vartial support for the dysregulation hypothesis of depression.
54A
25
Growth Hormone Secretion
GROWTH HORMONE RESPONSE TO ORAL YOHIMBINE IN PANIC DISORDER PATIENTS VERSUS CONTROLS Thomas W. Uhde, M.D., George Gurguis, M.D. National Institute of Mental Health, Bethesda, MD 20892. Panic disorder patients have blunted (growth hormone) GH responses to clonidine and to GRH relative to normal controls, indicating possible abnormalities in the noradrenergic control of GH release. We investigated the behavioral, neuroendocrine, and biochemical effects of oral yohimbine (20 rag) or placebo in I 1 panic disorder patients and 7 normal controls. Behavioral ratings and biological samples were obtained at baseline and at hourly intervals (up to 5 hr) after drug administration. There were no significant baseline differences between patients and controls in baseline levels of GH. No significant Group x Time interaction on ratings of anxiety or GH were noted after placebo. Yohimbine produced a significant main effect increase on ratings of anxiety, although the panic disorder patients had a greater anxiogemc response compared to normal controls. A transient but significant increase in GH levels occurred + 60 min after yohimbine. Panic patients had blunted l-hr GH responses compared to controls. There were no differences in peak GH levels between patients (n = 6) who panicked compared to ~ose who did not panic (n = 6) after yohimbine. Our observations suggest that panicogcnic doses of yohimbine may he associated with brief but significant increases in growth hormone. Blunted GH responses to yohimbine may represent further evidence of a hyporesponsive hypothalamic--GH system in panic disorder. Assuming that yohimbine completely blocks postsynaptic or-2 receptors in the hypothalamus, our data indicate that some anxiety states, even those induced by yohimbine, may be associated with increases in GH via mechanisms independent of ¢t-2 adrenergic receptors.
26
NON-LINEAR MULTIOSCILLATOR ANALYSES OF NORADRENERGIC AND NEUROENDOCRINE REGULATION IN DEPRESSION Robert L. Trestman, Ph.D., M.D., Martin H. Teicher, M.D., Ph.D., Emil F. Coccaro, M.D., David Harper, B.S., Vivian Mitropoulou, M.A., Steven Gabriel, Ph.D., Peter Knott, Ph.D., Larry J. Siever, M.D. Mt. Sinai School of Medicine~Bronx VAMC, New York, IVY 10029. The hypothesis of dysregulated monoamine/neuroendocrme systems in major depression implies that, compared to normal controls, i) the relative amplitude of circadian alterations in plasma metaboiites of these systems will be reduced or flattened, 2) the phase relationships among the monoamine/neumendocrine systems will be disturbed, and 3) normally dominant circadian rhythms will be replaced with higher frequency ultradian harmonics. Non-linear multioscillator cosinor analysis of serial plasma metabolite concentrations is a tool that allows these questions to be addressed. Concentrations of plasma MI-IPG were sampled hourly and plasma norepinep,hrine, cortisol, growth hormone, and prolactin were sampled at half hour intervals over 24 hr in 16 patients with acute major depression and 12 normal controls. Preliminary findings in a subsample of 13 acutely depressed patients and 6 normal controls revealed a decrease in circadian (p < 0.05) and a trend toward a decrease in ultradian (p < 0.1) relative amplitudes of plasma cortisoi, a phase advance of plasma MHPG (p < 0.05), and increased variability in MHPG rhythms in acutely depressed patients compared to normal controls. These results support the utility of the multioscillator model and offer vartial support for the dysregulation hypothesis of depression.