VOLKAN TOPÇUOĞLU, AYTÜL KARABEKİROĞLU, Çağrı YAZGAN

Panik bozukluğu provokasyon çalışmaları ve provokasyon ajanlarının farklılıkları

Amaç: Bu derlemede, panik bozukluğun patofizyolojisi hakkında provokasyon çalışmalarından elde edilen bilgiler bir araya getirilmiş ve provokasyon ajanları arasındaki farklılıklar ele alınmıştır. Yöntem: Derleme, Medline taraması yapılarak konu ile ilgili makalelere ulaşılması yolu ile yapılmıştır. Ayrıca, bazı kitap bölümleri ve Türkçe yayınlanmış makalelerden de yararlanılmıştır. Bulgular: Provokasyon ajanları, hipotalamus-hipofiz-adrenal (HPA) eksenine etkili olanlar ve solunum sistemine etkili olanlar olarak iki grupta incelenebilir. Solunum sistemine etkili olan sodyum (D,L) laktat, sodyum D-laktat, sodyum bikarbonat ve karbon dioksitin dispne ve hiperventilasyona yol açtıkları ancak HPA ekseninde etkinlik artışına neden olmadıkları belirlenmiştir. Bu ajanlar, panik bozukluk hastalarında aşırı duyarlı boğulma alarmı sistemini harekete geçirirler. HPA ekseninin etkinliğinde artışa neden olan yohimbin, m-klorofenilpiperazin ve fenfluramin ise solunum belirtilerine neden olmazlar. Provokasyon çalışmaları panik bozukluğun patofizyolojisinde lokus seruleusun yanında amigdala ve periakuaduktal gri bölgenin önemli beyin bölgeleri olduğunun anlaşılmasına yardımcı olmuştur. Sonuç: Provokasyon ajanları ile yapılan çalışmalar panik bozukluğun nöroanatomisi ve nörobiyolojisi hakkındaki bilgilerimizi arttırmıştır. Solunumsal provokasyon ajanlarının spontan panik ataklarını, HPA eksenine etki eden ajanların ise beklenti anksiyetesi veya duruma bağlı panik ataklarını incelemek için daha uygun modeller oldukları düşünülmektedir.

Anahtar Kelimeler:

Panik bozukluğu, Karbon dioksit, Kolesistokinin, Sodyum laktat

Provocation studies in panic disorder and the differences between provocation agents

Objective: Information obtained from the provocation studies on the pathophysiology of panic disorder are reviewed in this paper. Variations between the provocation agents are also discussed. Methods: A Medline search was performed to examine the literature on panic provocation studies. Some book chapters and articles written in Turkish were also studied. Results: Provocation agents could be investigated in two groups, as those effective on the hypothalamus-pituitary-adrenal axis (HPA) and those effective on the respiratory system. It has been determined that sodium (D,L) lactate, sodium D-lactate, sodium bicarbonate and carbon dioxide are effective on the respiratory system causing dyspnea and hyperventilation, however they do not increase the activity of the HPA axis. These respiratory panicogens activate the suffocation alarm system in patients with panic disorder. Yohimbine, m-chlorophenylpiperazine and fenfluramine that cause an increase in the activity of the HPA axis, do not provoke respiratory symptoms. Provocation studies have also identified that in pathophysiology of panic disorder, amigdala and periaquaductal grey region are also involved besides locus coeruleus. Conclusion: Studies using provocation agents have been usefull to understand the neuroanatomy and neurobiology of the panic disorder. It is assumed that respiratory panicogens are more suitable to investigate spontaneous panic attacks, and that the agents effective on HPA axis are more suitable to research anticipatory anxiety or situational panic attacks.

Keywords:

Panic Disorder, Carbon Dioxide, Cholecystokinin, Sodium Lactate,

PDF

___

1. Cohen ME, White PD. Life situations, emotions and neurocirculatory asthenia. Psychosom Med 1951; 13:335-357
2. Amerikan Psikiyatri Birliği. Mental Bozuklukların Tanısal ve Sayımsal Elkitabı. Dördüncü baskı (DSM-IV), Amerikan Psikiyatri Birliği, Washington DC, 1994, E Köroğlu (çev.), Ankara, Hekimler Yayın Birliği, 1996.
3. Griez E, Schruers K. Experimental pathophysiology of panic. J Psychosom Res 1998; 45:493-503.
4. Özcan ME, Levine LR, Potter WZ. Panic provocation studies with pfaceoo. Bull Clin Psychopharmacol'2000; 10:38-42.
5. Pitts FN, McClure JN. Lactate metabolism in anxiety neurosis. N Engl J Med 1967; 277:1329-1336.
6. Malizia AL, Nutt DJ. Brain mechanisms and circuits in panic disorder. DJ Nutt, JC Ballenger, JP Lepine (eds), Panic Disorder, Clinical Diagnosis, Management and Mechanisms. London, Martin Dunitz, 1999, s.55-77.
7. Gorman JM, Fyer MR, Liebowitz MR, Klein DF. Pharmacologic provocation of panic attacks. HY Meltzer (ed), Psychopharmacology: A Third Generation of Progress, New York, Raven Press, 1987, s.980-983.
8. Liebowitz MR, Fyer AJ, Gorman JM, Dillon D, Lewitt M, Klein DF. Specifity of lactate infusions in social phobia versus panic disorders. Am J Psychiatry 1985; 142:947-950.
9. Dillon DJ,: Gorman JM, Liebowitz MR, Fyer AJ, Klein DF. The measurement of lactate-induced panic and anxiety. Psychiatry Res 1987; 20:97-105.
10. Coplan JD, Klein DF. Pharmacological probes in panic disorder. HGM Westenberg, JA Den Boer, DL Murphy (eds), Advances in the Neurobiology of Anxiety Disorders. West Susex, John Wiley&Sons, 1996, s.173-196.
11. Carr. DB, Sheehan DV, Surman OS, Coleman JH, Grenblatt DJ, Heninger GR ve ark. Neuroendocrine correlates of lactate-induced anxiety and their response to chronic alprazolam therapy. Am J Psychiatry 1986;143:483-494.
12. Dager SR, Strauss WL, Marro Kl, Richards TL, Metzger GD, Artru AA. Proton magnetic resonance spectroscopy investigation of hyperventilation in subjects with panic disorder and comparison subjects. Am J Psychiatry 1995; 144:1080-1082.
13. Carr DB, Sheehan DV. Panic anxiety: a new biological model. J Clin Psychiatry 1984; 45:323-330.
14. Gibbs DM. Hyperventilation induced cerebral ischemia in panic disorder and effect of nimodipin. Am J Psychiatry 1992; 149:1589-1591.
15. Griez E, Verburg K. The current status of respiration in panic disorder. DJ Nutt, JC Ballenger, JP Lepine (eds), Panic Disorder, Clinical Diagnosis, Management and Mechanisms. London, Martin Dunitz, 1999, s.55-77.
16. Fyer MR, Uy J, Martinez J, Goetz R, Klein DF, Fyer A ve ark. CO2 challenge of patients with panic disorder. Am J Psychiatry 1987; 144:1080-1082.
17. Perna G, Battaglia M, Garberi A, Arancio C, Bertani A, Bellodi L. 35% CO2 / 65% O2 inhalation test in panic patients. Psychiatry Res 1994; 52:159-171.
18. Griez E, de Loof C, Pols H, Zandbergen J, Lousberg:H. Specific sensitivity of patients with panic attacks to carbon dioxide inhalation. Psychiatry Res 1990; 31:193-199.
19. Perna G, Barbini B, Cochi S, Bertani A, Gasperini M. 35% CO2 challenge in panic and' mood disorders. J Affect Disord 1995; 33:189-194.
20. Verburg C, Griez E, Meijer J, Pols H. Discrimination between panic disorder and generalized anxiety disorder with 35% carbon dioxide challenge. Am J Psychiatry 1995; 152:1081-1083.
21. Verburg C, Griez E, Meijer J. A 35% carbon dioxide challenge in simple phobia. Acta Psychiatrica Scand 1994; 90:420-423.
22. Perna G, Cocchi S, Bertani A, Arancio C, Bellodi L. 35% CO2 sensitivity in healthy first degree relatives of patients with panic disorder. Am J Psychiatry 1995; 152:623-625.
23. Papp LA, Klein DF, Gorman JM. Carbon dioxide hypersensitivity, hyperventilation and panic disorder. Am J Psychiatry 1993; 150:1149-1157.
24. Pine DS, Weese-Mayer DE, Silvestri JM, Davies M, Whitaker AH, Klein DF. Anxiety and congenital central hypoventilation syndrome. Am J Psychiatry 1994; 151:864-870.
25. Bourin M, Baker B, Bradwejn J. Neurobiology of panic disorder. J Psychosom Res 1998; 44:163-180.
26. Charney DS, Woods SW, KrystalJH. Noradrenergic neuronal dysregulation in panic disorder: the effects of intravenous yohimbine and clonidine in panic disorder. Acta Psychiatrica Scan 1992; 86:273-282.
27. Kent JM, Sullivan GM, Rauch SL. The neurobiology of fear: relevance to panic disorder and posttraumatic stress disorder. Psychiatr Ann 2000; 30:733-742.
28. Charney D, Woods S, Goodman W. Serotonin function in anxiety II: effects of serotonin agonist mCPP in panic disorder patients and healthy subjects. Psychopharmacology 1987; 92:14-24.
29. Kahn RS, Wetzler S. M-chlorophenylpiperazine as a probe of serotonin function. Biol Psychiatry 1991; 30:1139-1166.
30. Murphy DL, Mueller EA, Hill JL, Tolliver TJ, Jacobsen FM. Comparative anxiogenic, neuroendocrine, and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers. Psychopharmacology 1989; 98:275-282.
31. Faravelli C, Ricca V, Truglia E. Panic disorder: pathogenesis and treatment. EJL Griez, C Faravelli, D Nutt, J Zohar (eds), Anxiety Disorders an Introduction to Clinical Management and Research. West Sussex, John Wiley & Sons, 2001, s.81-103.
32. Katon W. Panic disorder in the medical setting. Washington DC, NiH Pub. No.93-3482, 1993, s.82.
33. Uhde TW, Boulanger JP, Vittone B, Jimerson DC, Post PM.. Caffeine: relationship to human anxiety, plasma HPG and cortisol. Psychopharmacol Bull 1984; 20:426-430.
34. Van Megen HJGM, Westenberg HGM, Den Boer JA, Kahn RS: Cholecystokinin in Panic Disorder. HGM Westenberg, JA Den Boer, DL Murphy (eds), Advances in the Neurobiology of Anxiety Disorders. West Susex, John Wiley & Sons, 1996, s.173-196.
35. Bradwejn J, Koszycki D, Meterissian G. Cholecys-tokinin-tetrapeptide induced panic attacks in patients with panic disorder. Can J Psychiatry 1990; 35:83-85.
36. Bradwejn J, Koszycki D, Shriqui C. Enhanced sensitivity to cholecystokinin tetrapeptide in panic disorder. Arch Gen Psychiatry 1991; 48:603-610.
37. Bradwejn J, Koszycki D. Imipramine antagonism of the panicogenic effects of cholecystokinin tetrapeptide in panic disorder patients. Am J Psychiatry 1994; 151:261-263.
38. Bradwejn N, Koszycki D, Couetoux du tertre A, Van Megen HJGM, Den Boer J, Westenberg H ve ark. The panicogenic effects of cholecystokinin-tetrapeptide are antagonized by L-365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder. Arch Gen Psychiatry 1994; 51:486-493.
39. Lines C, Challenor J, Traub M. Cholecytokinin and anxiety in normal volunteers: an investigation of the anxiogenic properties of pentagastrin and reversal by the cnolecytokinin receptor subtype B antagonist L-365,260. Br J Pharmacol 1995; 39:235-242.
40. Kramer MS, Cutler NR, Ballenger JC, Patterson WM, Mendels J, Chenault A ve ark. A placebo-controlled trial of L-365,260, a CCK-B antagonist, in panic disorder. Biol Psychiatry 1995; 37:462-466.
41. Bradwejn J. Koszycki D, Paradis M, Recee P, Hinton J, Sedman A. Effects of CI-988 on cholecytokinin tetra-peptide-induced panic symptoms in healty volunteers. Biol Psychiatry 1995; 38:742-746.
42. Van Megen HJGM, Westenberg HGM, Den Boer JA, Slaap B, van Es-Radhakishun F, Pande AC. The choie-cytokinin-B reseptör antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients. Psychopharmacolgy 1997; 129:243-248.
43. Coplan JD, Liebowitz MR, Gorman JM, Fyer AJ, Dillon DJ, Campeas RB ve ark. Noradrenergic function in panic disorder: clonidine pretreatment of sodium lactate infusions. Biol Psychiatry 1992; 31:135-146.
44. Charney OS, 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.
45. Deakin JFW, Graeff FG. 5-HT and mechanisms of defence. J Psychopharmacol 1991; 5:305-315.
46. Coplan JD, Lydiard RB. Brain circuits in panic disorder. Biol Psychiatry 1998; 44:1264-1276.
47.Alkın T. Panik bozukluğun işlevsel nöroanatomisi: Beyin on yıl öncesi ve sonrası. 3P Dergisi 2001; 9:557-574.