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Heart Rate and Plasma Norepinephrine Responsivity to Orthostatic Challenge in Anxiety Disorders: Comparison of Patients With Panic Disorder and Social Phobia and Normal Control Subjects

Heart Rate and Plasma Norepinephrine Responsivity to Orthostatic Challenge in Anxiety Disorders:... Abstract Heart rate and plasma norepinephrine responsivity to a physiologic challenge, ie, orthostasis, were measured in 20 patients with panic disorder (PD) and 20 age- and sex-matched normal control subjects. While the two groups exhibited similar supine heart rates, patients with PD had a significantly greater heart rate response to orthostatic challenge. Plasma norepinephrine responses did not differ between patients with PD and normal control subjects. In a matched subgroup of 14 patients with PD, 14 normal control subjects, and 14 patients with social phobia, the patients with social phobia exhibited supine and upright plasma norepinephrine levels that were significantly higher than those of the other two diagnostic groups. Taken together, and in the context of findings from other studies, these preliminary observations suggest that the anxiety disorders may demonstrate differing patterns of autonomic dysfunction. Back to top Article Information Accepted for publication July 3, 1991. Presented at the 29th Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico, December 12, 1990. Reprint requests to Section on Anxiety and Affective Disorders, Biological Psychiatry Branch, Bldg 10, Room 3S-239, 9000 Rockville Pike, Bethesda, MD 20892 (Dr Uhde). The authors wish to thank Lisa Eisen and Diana Roscow for assistance with data management, Melanie Dubin for assistance with manuscript preparation, and Ingrid Hutter and Carolyn Masters for expert assistance with the norepinephrine assay. We also wish to thank Husseini Manji, MD, for his thoughtful review of an earlier version of the manuscript. References 1. Cameron OG, Nesse RM. Systemic hormonal and physiological abnormalities in anxiety disorders. Psychoneuroendocrinology. 1988;13:287-307. PubMedGoogle ScholarCrossref 2. Ballenger JC, Peterson GA, Laraia M, Hudek A, Lake CR, Jimerson D, Cox DJ, Trockman C, Shipe JR, Wilkinson C. A study of plasma catecholamines in agoraphobia and the relationship of serum tricyclic levels to treatment response. In: Ballenger JC, ed. Biology of Agoraphobia. Washington, DC: American Psychiatric Press Inc; 1984:27-63.Google Scholar 3. Nesse RM, Cameron OG, Curtis GC, McCann DS, Huber-Smith MJ. Adrenergic function in patients with panic anxiety. Arch Gen Psychiatry. 1984;41:771-776. PubMedGoogle ScholarCrossref 4. Villacres EC, Hollifield M, Katon WJ, Wilkinson WC, Veith RC. Sympathetic nervous system activity in panic disorder. Psychiatry Res. 1987;21:313-321. PubMedGoogle ScholarCrossref 5. Nesse RM, Cameron OG, Buda AJ, McCann DS, Curtis CG, Huber-Smith MJ. Urinary catecholamines and mitral valve prolapse in panic anxiety patients. Psychiatry Res. 1985;14:67-74. PubMedGoogle ScholarCrossref 6. Garvey MJ, Tollefson GD, Orsulak PJ. Elevations of urinary MHPG in depressed patients with panic attacks. Psychiatry Res. 1987;20:183-187. PubMedGoogle ScholarCrossref 7. Cameron OC, Smith CB, Lee MA, Hollingsworth PJ, Hill EM, Curtis GC. Adrenergic function in anxiety disorders: platelet α2-adrenergic receptor binding, blood pressure, pulse, and plasma catecholamines in panic and generalized anxiety disorder patients and normal subjects. Biol Psychiatry. 1990;28:3-20. PubMedGoogle ScholarCrossref 8. Edlund MJ, Swann AC, Davis CM. Plasma MHPG in untreated panic disorder. Biol Psychiatry. 1987;22:1488-1491. PubMedGoogle ScholarCrossref 9. Crow A, Glover V, Weg MW, Walker PL, Sheehan DV, Carr DB, Sandler M. Urinary catecholamine metabolite and tribulin output during lactate infusion. Br J Psychiatry. 1988;152:122-126. PubMedGoogle ScholarCrossref 10. Uhde TW, Joffe RT, Jimerson DC, Post RM. Normal urinary free cortisol and plasma MHPG in panic disorder: clinical and theoretical implications. Biol Psychiatry. 1988;23:575-585. PubMedGoogle ScholarCrossref 11. Gurguis GNM, Uhde TW. Plasma 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG) and growth hormone responsis to yohimbine in panic disorder patients and normal controls. Psychoneuroendocrinology. 1990;15:217-224. PubMedGoogle ScholarCrossref 12. Charney DS, Heninger GR, Breier A. Noradrenergic function in panic anxiety: effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1984;41:751-763. PubMedGoogle ScholarCrossref 13. Charney DS, Heninger GR. Abnormal regulation of noradrenergic function in panic disorders: effects of clonidine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1986;43:1042-1054. PubMedGoogle ScholarCrossref 14. Nutt DJ. Altered central α2-adrenoceptor sensitivity in panic disorder. Arch Gen Psychiatry. 1989;46:165-169. PubMedGoogle ScholarCrossref 15. Uhde TW, Stein MB, Vittone BJ, Siever LJ, Boulenger J-P, Klein E, Mellman TA. Behavioral and physiologic effects of short-term and long-term administration of clonidine in panic disorder. Arch Gen Psychiatry. 1989;46:170-177. PubMedGoogle ScholarCrossref 16. Pohl R, Yeragani VK, Balon R, Rainey JM, Lycaki H, Ortiz A, Berchou R, Weinberg P. lsoproterenol-induced panic attacks. Biol Psychiatry. 1988;24:891-902. PubMedGoogle ScholarCrossref 17. Cameron OG, Smith CB, Hollingsworth PJ, Nesse RM, Curtis GC. Platelet α2-adrenergic receptor binding and plasma catecholamines: before and during imipramine treatment in patients with panic anxiety. Arch Gen Psychiatry. 1984;41:1144-1148. PubMedGoogle ScholarCrossref 18. Nutt DJ, Frazer S. Platelet binding studies in panic disorder. J Affective Disord. 1987;12:7-11. PubMedGoogle ScholarCrossref 19. Norman TR, Kimber NM, Judd FK, Burrows GD, Mclntyre IM. Platelet 3H-Rauwolscine binding in patients with panic attacks. Psychiatry Res. 1987;22:43-48. PubMedGoogle ScholarCrossref 20. Charney DS, Innis RB, Duman RS, Woods SW, Heninger GR. Platelet α-2-receptor binding and adenylate cyclase activity in panic disorder. Psychopharmacology (Berl). 1989;98:102-107. PubMedGoogle ScholarCrossref 21. Brown S-L, Charney DS, Woods WS, Heninger GR, Tallman J. Lymphocyte β-adrenergic receptor binding in panic disorder. Psychopharmacology. 1988;94:24-28. PubMedGoogle ScholarCrossref 22. Lima DR, Turner P. Propranolol increases reduced β-receptor function in severely anxious patients. Lancet. 1983;2:1505. PubMedGoogle ScholarCrossref 23. Liebowitz MR, Gorman JM, Fyer AJ, Dillon D, Levy G, Appleby IL, Anderson S, Palij M, Davies SO, Klein DF. Lactate provocation of panic attacks, II: biochemical and physiologic findings. Arch Gen Psychiatry. 1985;42:709-719. PubMedGoogle ScholarCrossref 24. Yeragani VK, Pohl R, Rainey JM, Balon R, Ortiz A, Lycaki H, Gershon S. Pre-infusion heart rates and laboratory-induced panic attacks. Acta Psychiatr Scand. 1987;75:51-54. PubMedGoogle ScholarCrossref 25. Freedman RR, lanni P, Ettedgui E, Nandakumaran P. Ambulatory monitoring of panic disorder. Arch Gen Psychiatry. 1985;42:244-248. PubMedGoogle ScholarCrossref 26. Shear MK, Kligfield P, Hershfield G, Devereux RB, Polan J, Mann JJ, Pickering T, Frances AJ. Cardiac rate and rhythm in panic patients. Am J Psychiatry. 1987;144:633-637. PubMedGoogle ScholarCrossref 27. Balon R, Ortiz A, Pohl R, Yeragani VK. Heart rate and blood pressure during placebo-associated panic attacks. Psychosom Med. 1988;50:434-438. PubMedGoogle ScholarCrossref 28. Taylor CB, Sheikh J, Agras WS, Roth WT, Margraf J, Ehlers A, Maddock RJ, Gossard D. Ambulatory heart rate changes in patients with panic attacks. Am J Psychiatry. 1986;143:478-482. PubMedGoogle ScholarCrossref 29. Cameron OG, Lee MA, Curtis GC, McCann DS. Endocrine and physiological changes during 'spontaneous' panic attacks. Psychoneuroendocrinology. 1987;12:321-331. PubMedGoogle ScholarCrossref 30. White WB, Baker LH. Episodic hypertension secondary to panic disorder. Arch Intern Med. 1986;146:1129-1130. PubMedGoogle ScholarCrossref 31. Woods SW, Charney DS, McPherson CA, Gradman AH, Heninger GR. Situational panic attacks. Arch Gen Psychiatry. 1987;44:365-375. PubMedGoogle ScholarCrossref 32. Ko GN, Elsworth JD, Roth RH, Rifkin BG, Leigh H, Redmond DE Jr.. Panic-induced elevation of plasma MHGP levels in phobic-anxious patients: effects of clonidine and imipramine. Arch Gen Psychiatry. 1983;40:425-430. PubMedGoogle ScholarCrossref 33. Rudorfer MV, Ross RJ, Linnoila M, Sherer MA, Potter WZ. Exaggerated orthostatic responsivity of plasma norepinephrine in depression. Arch Gen Psychiatry. 1985;42:1186-1192. PubMedGoogle ScholarCrossref 34. Roy A, Pickar D, Linnoila M, Potter WZ. Plasma norepinephrine level in affective disorders: relationship to melancholia. Arch Gen Psychiatry. 1985;42:1181-1185. PubMedGoogle ScholarCrossref 35. Breier A, Charney DS, Heninger GR. Major depression in patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1984;41:1129-1135. PubMedGoogle ScholarCrossref 36. Uhde TW, Boulenger J-P, Roy-Byrne PP, Vittone BJ, Post RM. Longitudinal course of panic disorder: clinical and biological considerations. Prog Neuropsychopharmacol Biol Psychiatry. 1985;9:39-51. PubMedGoogle ScholarCrossref 37. Stein MB, Uhde TW. Panic disorder and major depression: a tale of two syndromes. Psychiatr Clin North Am. 1988;11:441-461. PubMedGoogle Scholar 38. Stein MB, Uhde TW. Panic disorder and major depression: lifetime relationship and biological markers. In: Ballenger J, ed. Clinical Aspects of Panic Disorder. New York, NY: John Wiley & Sons Inc; 1990:151-168.Google Scholar 39. Heninger GR. Evidence for comorbidity: biologic studies. 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Heart Rate and Plasma Norepinephrine Responsivity to Orthostatic Challenge in Anxiety Disorders: Comparison of Patients With Panic Disorder and Social Phobia and Normal Control Subjects

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American Medical Association
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Copyright © 1992 American Medical Association. All Rights Reserved.
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0003-990X
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1598-3636
DOI
10.1001/archpsyc.49.4.311
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Abstract

Abstract Heart rate and plasma norepinephrine responsivity to a physiologic challenge, ie, orthostasis, were measured in 20 patients with panic disorder (PD) and 20 age- and sex-matched normal control subjects. While the two groups exhibited similar supine heart rates, patients with PD had a significantly greater heart rate response to orthostatic challenge. Plasma norepinephrine responses did not differ between patients with PD and normal control subjects. In a matched subgroup of 14 patients with PD, 14 normal control subjects, and 14 patients with social phobia, the patients with social phobia exhibited supine and upright plasma norepinephrine levels that were significantly higher than those of the other two diagnostic groups. Taken together, and in the context of findings from other studies, these preliminary observations suggest that the anxiety disorders may demonstrate differing patterns of autonomic dysfunction. Back to top Article Information Accepted for publication July 3, 1991. Presented at the 29th Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico, December 12, 1990. Reprint requests to Section on Anxiety and Affective Disorders, Biological Psychiatry Branch, Bldg 10, Room 3S-239, 9000 Rockville Pike, Bethesda, MD 20892 (Dr Uhde). The authors wish to thank Lisa Eisen and Diana Roscow for assistance with data management, Melanie Dubin for assistance with manuscript preparation, and Ingrid Hutter and Carolyn Masters for expert assistance with the norepinephrine assay. We also wish to thank Husseini Manji, MD, for his thoughtful review of an earlier version of the manuscript. References 1. Cameron OG, Nesse RM. Systemic hormonal and physiological abnormalities in anxiety disorders. Psychoneuroendocrinology. 1988;13:287-307. PubMedGoogle ScholarCrossref 2. Ballenger JC, Peterson GA, Laraia M, Hudek A, Lake CR, Jimerson D, Cox DJ, Trockman C, Shipe JR, Wilkinson C. A study of plasma catecholamines in agoraphobia and the relationship of serum tricyclic levels to treatment response. In: Ballenger JC, ed. Biology of Agoraphobia. Washington, DC: American Psychiatric Press Inc; 1984:27-63.Google Scholar 3. Nesse RM, Cameron OG, Curtis GC, McCann DS, Huber-Smith MJ. Adrenergic function in patients with panic anxiety. Arch Gen Psychiatry. 1984;41:771-776. PubMedGoogle ScholarCrossref 4. Villacres EC, Hollifield M, Katon WJ, Wilkinson WC, Veith RC. Sympathetic nervous system activity in panic disorder. Psychiatry Res. 1987;21:313-321. PubMedGoogle ScholarCrossref 5. Nesse RM, Cameron OG, Buda AJ, McCann DS, Curtis CG, Huber-Smith MJ. Urinary catecholamines and mitral valve prolapse in panic anxiety patients. Psychiatry Res. 1985;14:67-74. PubMedGoogle ScholarCrossref 6. Garvey MJ, Tollefson GD, Orsulak PJ. Elevations of urinary MHPG in depressed patients with panic attacks. Psychiatry Res. 1987;20:183-187. PubMedGoogle ScholarCrossref 7. Cameron OC, Smith CB, Lee MA, Hollingsworth PJ, Hill EM, Curtis GC. Adrenergic function in anxiety disorders: platelet α2-adrenergic receptor binding, blood pressure, pulse, and plasma catecholamines in panic and generalized anxiety disorder patients and normal subjects. Biol Psychiatry. 1990;28:3-20. PubMedGoogle ScholarCrossref 8. Edlund MJ, Swann AC, Davis CM. Plasma MHPG in untreated panic disorder. Biol Psychiatry. 1987;22:1488-1491. PubMedGoogle ScholarCrossref 9. Crow A, Glover V, Weg MW, Walker PL, Sheehan DV, Carr DB, Sandler M. Urinary catecholamine metabolite and tribulin output during lactate infusion. Br J Psychiatry. 1988;152:122-126. PubMedGoogle ScholarCrossref 10. Uhde TW, Joffe RT, Jimerson DC, Post RM. Normal urinary free cortisol and plasma MHPG in panic disorder: clinical and theoretical implications. Biol Psychiatry. 1988;23:575-585. PubMedGoogle ScholarCrossref 11. Gurguis GNM, Uhde TW. Plasma 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG) and growth hormone responsis to yohimbine in panic disorder patients and normal controls. Psychoneuroendocrinology. 1990;15:217-224. PubMedGoogle ScholarCrossref 12. Charney DS, Heninger GR, Breier A. Noradrenergic function in panic anxiety: effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1984;41:751-763. PubMedGoogle ScholarCrossref 13. Charney DS, Heninger GR. Abnormal regulation of noradrenergic function in panic disorders: effects of clonidine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1986;43:1042-1054. PubMedGoogle ScholarCrossref 14. Nutt DJ. Altered central α2-adrenoceptor sensitivity in panic disorder. Arch Gen Psychiatry. 1989;46:165-169. PubMedGoogle ScholarCrossref 15. Uhde TW, Stein MB, Vittone BJ, Siever LJ, Boulenger J-P, Klein E, Mellman TA. Behavioral and physiologic effects of short-term and long-term administration of clonidine in panic disorder. Arch Gen Psychiatry. 1989;46:170-177. PubMedGoogle ScholarCrossref 16. Pohl R, Yeragani VK, Balon R, Rainey JM, Lycaki H, Ortiz A, Berchou R, Weinberg P. lsoproterenol-induced panic attacks. Biol Psychiatry. 1988;24:891-902. PubMedGoogle ScholarCrossref 17. Cameron OG, Smith CB, Hollingsworth PJ, Nesse RM, Curtis GC. Platelet α2-adrenergic receptor binding and plasma catecholamines: before and during imipramine treatment in patients with panic anxiety. Arch Gen Psychiatry. 1984;41:1144-1148. PubMedGoogle ScholarCrossref 18. Nutt DJ, Frazer S. Platelet binding studies in panic disorder. J Affective Disord. 1987;12:7-11. PubMedGoogle ScholarCrossref 19. Norman TR, Kimber NM, Judd FK, Burrows GD, Mclntyre IM. Platelet 3H-Rauwolscine binding in patients with panic attacks. Psychiatry Res. 1987;22:43-48. PubMedGoogle ScholarCrossref 20. Charney DS, Innis RB, Duman RS, Woods SW, Heninger GR. Platelet α-2-receptor binding and adenylate cyclase activity in panic disorder. Psychopharmacology (Berl). 1989;98:102-107. PubMedGoogle ScholarCrossref 21. Brown S-L, Charney DS, Woods WS, Heninger GR, Tallman J. Lymphocyte β-adrenergic receptor binding in panic disorder. Psychopharmacology. 1988;94:24-28. PubMedGoogle ScholarCrossref 22. Lima DR, Turner P. Propranolol increases reduced β-receptor function in severely anxious patients. Lancet. 1983;2:1505. PubMedGoogle ScholarCrossref 23. Liebowitz MR, Gorman JM, Fyer AJ, Dillon D, Levy G, Appleby IL, Anderson S, Palij M, Davies SO, Klein DF. Lactate provocation of panic attacks, II: biochemical and physiologic findings. Arch Gen Psychiatry. 1985;42:709-719. PubMedGoogle ScholarCrossref 24. Yeragani VK, Pohl R, Rainey JM, Balon R, Ortiz A, Lycaki H, Gershon S. Pre-infusion heart rates and laboratory-induced panic attacks. Acta Psychiatr Scand. 1987;75:51-54. PubMedGoogle ScholarCrossref 25. Freedman RR, lanni P, Ettedgui E, Nandakumaran P. Ambulatory monitoring of panic disorder. Arch Gen Psychiatry. 1985;42:244-248. PubMedGoogle ScholarCrossref 26. Shear MK, Kligfield P, Hershfield G, Devereux RB, Polan J, Mann JJ, Pickering T, Frances AJ. Cardiac rate and rhythm in panic patients. Am J Psychiatry. 1987;144:633-637. PubMedGoogle ScholarCrossref 27. Balon R, Ortiz A, Pohl R, Yeragani VK. Heart rate and blood pressure during placebo-associated panic attacks. Psychosom Med. 1988;50:434-438. PubMedGoogle ScholarCrossref 28. Taylor CB, Sheikh J, Agras WS, Roth WT, Margraf J, Ehlers A, Maddock RJ, Gossard D. Ambulatory heart rate changes in patients with panic attacks. Am J Psychiatry. 1986;143:478-482. PubMedGoogle ScholarCrossref 29. Cameron OG, Lee MA, Curtis GC, McCann DS. Endocrine and physiological changes during 'spontaneous' panic attacks. Psychoneuroendocrinology. 1987;12:321-331. PubMedGoogle ScholarCrossref 30. White WB, Baker LH. Episodic hypertension secondary to panic disorder. Arch Intern Med. 1986;146:1129-1130. PubMedGoogle ScholarCrossref 31. Woods SW, Charney DS, McPherson CA, Gradman AH, Heninger GR. Situational panic attacks. Arch Gen Psychiatry. 1987;44:365-375. PubMedGoogle ScholarCrossref 32. Ko GN, Elsworth JD, Roth RH, Rifkin BG, Leigh H, Redmond DE Jr.. Panic-induced elevation of plasma MHGP levels in phobic-anxious patients: effects of clonidine and imipramine. Arch Gen Psychiatry. 1983;40:425-430. PubMedGoogle ScholarCrossref 33. Rudorfer MV, Ross RJ, Linnoila M, Sherer MA, Potter WZ. Exaggerated orthostatic responsivity of plasma norepinephrine in depression. Arch Gen Psychiatry. 1985;42:1186-1192. PubMedGoogle ScholarCrossref 34. Roy A, Pickar D, Linnoila M, Potter WZ. Plasma norepinephrine level in affective disorders: relationship to melancholia. Arch Gen Psychiatry. 1985;42:1181-1185. PubMedGoogle ScholarCrossref 35. 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Journal

Archives of General PsychiatryAmerican Medical Association

Published: Apr 1, 1992

Keywords: norepinephrine,heart rate,anxiety disorders,panic disorder,plasma,social phobia

References