Abstract
Objective
Panic disorder (PD) has been associated with an increased risk for cardiovascular (CV) morbidity and mortality. There are inconsistent reports of increased low-density lipoprotein cholesterol (LDL-C) in patients with PD. Studies have reported a correlation between cholesterol levels and the intensity and frequency of panic attacks (PAs), suggesting that an elevation in cholesterol could be due to physiological and neurochemical changes that occur during and after a PA. The objective of our study was to show that the occurrence of a PA is associated with an increase in LDL-C.
Materials and methods
We used a double-blind, placebo-controlled crossover design with randomized injections of placebo and pentagastrin in 18 patients with PD (11 men, 7 women) and 33 healthy-control subjects (24 men, 9 women).
Results
Pentagastrin-induced PAs were associated with a statistically significant 10.4% delayed (24 h) increase in LDL-C levels in male subjects. Such an effect was not observed in female subjects.
Conclusion
LDL-C levels are directly affected by the occurrence of a PA in males. These findings, in association with previous reports of increased cholesterol levels in PD patients, suggest that a chronic increase in LDL-C as a result of frequent PAs may be one of the mechanisms that contributes, at least in male patients, to previously reported increased CV risk in patients with PD. The gender difference and the temporal association between PAs and increased LDL-C may explain the inconsistency in the findings of previous investigations of cholesterol levels in PD patients.
Similar content being viewed by others
References
Abelson JL, Nesse RM (1994) Pentagastrin infusions in patients with panic disorder I. Symptoms and cardiovascular response. Biol Psychiatry 36:73–83
Abelson JL, Liberzon I, Young EA, Khan S (2005) Cognitive modulation of the endocrine stress response to a pharmacological challenge in normal and panic disorder subjects. Arch Gen Psychiatry 62:668–675
Agargun MY, Kara H, Algun E, Sekeroglu R, Trakcioglu M (1996) High cholesterol levels in patients with sleep panic. Biol Psychiatry 40:1064–1065
Bachen EA, Muldoon MF, Matthews KA, Manuck SB (2002) Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress. Psychosom Med 64:587–594
Bajwa WK, Asnis GM, Sanderson WC, Irfan A, van Pragg HM (1992) High cholesterol levels in patients with panic disorder. Am J Psychiatry 149:376–378
Barnett JB, Woods MN, Lamon-Fava S, Schaefer EJ, McNamara JR, Spiegelman D, Hertzmark E, Goldin B, Longcope C, Gorbach SL (2004) Plasma lipid and lipoprotein levels during the follicular and luteal phases of the menstrual cycle. J Clin Endocrinol Metab 89:776–782
Bradwejn J, Koszycki D, Shriqui C (1991) Enhanced sensitivity to cholecystokinin tetrapeptide in panic disorder; clinical and behavioral findings. Arch Gen Psychiatry 48:603–610
Coryell W, Noyes R, Clancy J (1982) Excess mortality in panic disorder. Arch Gen Psychiatry 39:701–703
Coryell W, Noyes R, House D (1986) Mortality among outpatients with anxiety disorders. Am J Psychiatry 143:508–510
Dakak N, Quyyumi AA, Eisenhofer G, Goldstein DS, Cannon RO (1995) Sympathetically mediated effects of mental stress on the cardiac microcirculation of patients with coronary artery disease. Am J Cardiol 76:125–130
Fleet R, Lavoie K, Beitman BD (2000) Is panic disorder associated with coronary artery disease? A critical review of the literature. J Psychosom Res 48:347–356
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502
Gaziano MJ, Manson JE, Ridker PM (2005) Primary and secondary prevention of coronary heart disease. In: Zipes DP, Libby P, Bonow RO, Braunwald E (eds) Braunwald’s heart disease: a textbook of cardiovascular medicine. Saunders, Philadelphia, PA, p 1068
Grundy SM, Cleeman JI, Merz CNB, Brewer HB, Clar LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ (2004) Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation 110:227–239
Haines AP, Imeson JD, Meade TW (1987) Phobic anxiety and ischaemic heart disease. BMJ 295:297–299
Hayward C, Taylor CB, Roth WT, King R, Agras WS (1989) Plasma lipid levels in patients with panic disorder or agoraphobia. Am J Psychiatry 146:917–919
Herd JA (1983) Physiological basis for behavioral influences in arteriosclerosis. In: Dembroski TM, Schmidt TH, Blumchen G (eds) Biobehavioural basis of coronary heart disease. Karger, Basel, pp 248–256
Kawachi I, Colditz GA, Ascherio A, Rimm EB, Giovannucci E, Stampfer MJ, Willett WC (1994) Coronary heart disease/myocardial infarction: prospective study of phobic anxiety and the risk of coronary heart disease in men. Circulation 89:1992–1997
Khan S, Liberzon I, Abelson JL (2004) Effects of propranolol on symptom and endocrine responses to pentagastrin. Psychoneuroendocrinology 29:1163–1171
Krantz DS, Kop WJ, Santiago HT, Gottdiener JS (1996) Mental stress as a trigger of myocardial ischemia and infarction. Cardiol Clin 14:271–287
Lara N, Baker GB, Archer SL, Le Mellédo JM (2003) Increased cholesterol levels during paroxetine administration in healthy men. J Clin Psychiatry 64:1455–1459
LeMellédo J-M, Bradwejn J, Koszycki D, Bichet DG, Bellavance F (1998) The role of the β-noradrenergic system in cholecystokinin-tetrapeptide-induced panic symptoms. Biol Psychiatry 44:364–366
Liebowitz MR, Gelenberg AJ, Munjack D (2005a) Venlafaxine extended release vs. placebo and paroxetine in social anxiety disorder. Arch Gen Psychiatry 65:190–198
Liebowitz MR, Mangano RM, Bradwejn J, Asnis G (2005b) A randomized controlled trial of venlafazine extended release in generalized anxiety disorder. J Clin Psychiatry 66:238–247
McCann BS, Carter J, Vaughan M, Raskind M, Wilkinson CW, Veith RC (1993) Cardiovascular and neuroendocrine responses to extended laboratory challenge. Psychosom Med 55:497–504
McCann BS, Magee MS, Broyles FC, Vaughan M, Alber JJ, Knopp RH (1995) Acute psychological stress and epinephrine infusion in normolipidemic and hyperlipidemic men: effects on plasma lipid and apoprotein concentrations. Psychosom Med 57:165–176
Morrow JD, McManus K, Tait GR, Bellavance F, Chrapko W, Lara N, Le Mellédo J-M (2003) Pentagastrin-induced release of free fatty acids in healthy volunteers and patients with panic disorder: effect of pretreatment with ethinyl estradiol. J Psychiatry Neurosci 28:127–133
Muldoon MF, Herbert TB, Patterson SM, Kameneva M, Raible R, Manuck SB (1992) Acute cholesterol responses to mental stress and change in posture. Arch Intern Med 152:775–780
Muldoon MF, Bachen EA, Manuck SB, Waldstein SR, Bricker PL, Bennett JA (1995) Effects of acute psychological stress on serum lipid levels, hemoconcentration and blood viscosity. Arch Intern Med 155:615–620
Patterson SM, Gottdiener JS, Hecht G, Vargot S, Krant DS (1993) Effects of acute psychological stress on serum lipids: mediating effects of plasma volume. Psychosom Med 55:525–532
Peter H, Hand I, Hohagen F, Koenig A, Mindermann O, Oeder F, Wittich M (2002) Serum cholesterol level comparison: control subjects, anxiety disorder patients, and obsessive compulsive disorder patients. Can J Psychiatry 47:557–561
Rickels K, Mangano R, Khan A (2004) A double blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder. J Clin Psychopharmacol 24:488–496
Schneiderman N (1983) Behavior, autonomic function and animal models of cardiovascular pathology. In: Dembroski TM, Schmidt TH, Blumchen G (eds) Biobehavioural basis of coronary heart disease. Karger, Basel, pp 304–364
Shioiri T, Fujii K, Someya T, Takahashi S (2000) Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study. J Affect Disord 58:167–170
Steiner G, Poapst ME, Shumak SL, Foster DM (1986) Metabolism of apolipoprotein B-containing lipoproteins. Methods Enzymol 129:395–440
Tancer ME, Stein MB, Moul DE, Uhde TU (1990) Normal serum cholesterol in panic disorder. Biol Psychiatry 27:99–101
Van Megen HJ, Westenberg HG, den Boer JA, Haigh JR, Traub M (1994) Pentagastrin induced panic attacks: enhanced sensitivity in panic disorder patients. Psychopharmacology 114:449–455
Van Megen HJ, Westenberg HG, den Boer JA, Kahn RS (1996) Cholecystokinin in anxiety. Eur Neuropsychopharmacol 6:263–280
Weissman MM, Markowitz JS, Ouellette R, Greenwald S, Kahn JP (1990) Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey. Am J Psychiatry 147:1504–1508
Yeragani VK, Balon R, Pohl R, Ramesh C, Glitz D, Weinberg P, Merlos B (1990) Decreased R-R variance in panic disorder patients. Acta Psychiatr Scand 81:554–559
Acknowledgments
This research was sponsored by operating grants of the University of Alberta Hospital Foundation and the Canadian Institutes of Health Research (CIHR) grant to JMLM. JMLM is an AHFMR (Alberta Heritage Foundation for Medical Research) scholar. The authors thank Janisse Khudabux, R.N. for her assistance in the development and execution of the study. The authors also thank the Laboratory of Medicine at the University of Alberta Hospital for lipid measurements.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Perez-Parada, J., Jhangri, G.S., Lara, N. et al. Delayed increase in LDL cholesterol following pentagastrin-induced panic attacks. Psychopharmacology 193, 333–340 (2007). https://doi.org/10.1007/s00213-007-0759-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-007-0759-2