Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-17T17:13:09.913Z Has data issue: false hasContentIssue false
  • English
  • Français

The genetics of panic disorder: state of the art

Published online by Cambridge University Press:  24 June 2014

Dirk van West  and
Stephan Claes
Dirk van West
Affiliation:
Department of Molecular Genetics, University of Antwerp (UIA) University Centre of Child and Adolescent Psychiatry Antwerp (UCKJA) Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp (UIA), Antwerp, Belgium
Stephan Claes*
Affiliation:
Department of Molecular Genetics, University of Antwerp (UIA) Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp (UIA), Antwerp, Belgium
*
Professor Stephan Claes MD PhD, Department of Molecular Genetics, University of Antwerp (UA/UIA), Universiteitsplein 1, B-2610 Antwerpen, Belgium. Tel: +32 3820 23 21; Fax: +32 3820 25 41; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Panic disorder (PD) is a highly prevalent, debilitating disorder. The heritability of the disease has been estimated by twin studies to be between 30 and 60%. The vulnerability for PD overlaps with an increased risk of bipolar disorder in some families. Classical genetic methods such as linkage analysis and association studies have not yet identified genetic risk factors beyond doubt. However, two independent studies confirm linkage of a specific syndrome characterized by PD, bladder problems, severe headaches, mitral valve prolapse and thyroid dysfunction to genetic markers on chromosome 13q. Association studies, although showing divergent results, give some support to a causative role for the genes encoding for monoamine oxidase A (MAO-A), cholecystokinin (CCK) and catechol-O-methyltransferase (COMT). Finally, a somatic duplication of a 19-Mb region on chromosome 15 has been associated with PD, but this intriguing finding awaits confirmation.

Keywords

DUP25geneticspanic disorder
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 16 , Issue 2 , April 2004 , pp. 68 - 78
Copyright
Copyright © 2004 Blackwell Munksgaard

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Klein, DF. Delineation of two drug–responsive anxiety syndromes. Psychopharmacol 1964;5: 397–408. CrossRefGoogle ScholarPubMed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association, 1994. Google ScholarPubMed
Weissman, MM, Bland, RC, Canino, GJet al. The crossnational epidemiology of panic disorder. Arch General Psychiatry 1997;54: 305–309. CrossRefGoogle Scholar
van den Heuvel, OA, van de Wetering, BJ, Veltman, DJ, Pauls, DL. Genetic studies of panic disorder: a review. J Clin Psychiatry 2000;6: 756–766. CrossRefGoogle Scholar
Crowe, RR, Noyes, R, Pauls, DL, Slymen, D. A family study of panic disorder. Arch General Psychiatry 1983;40: 1065–1069. CrossRefGoogle ScholarPubMed
Fyer, AJ, Mannuzza, S, Chapman, TF, Lipsitz, J, Martin, LY, Klein, DF. Panic disorder and social phobia: effects of comorbidity on familial transmission. Anxiety 1996;2: 173–178.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
Maier, W, Lichtermann, D. The genetic epidemiology of unipolar depression and panic disorder. Int Clin Psychopharmacol 1993;8(Suppl. 1):27–33.CrossRefGoogle ScholarPubMed
Mendlewicz, J, Papadimitriou, G, Wilmotte, J. Family study of panic disorder: comparison with generalized anxiety disorder, major depression, and normal subjects. Psychiatry Genet 1993;3: 73–78. CrossRefGoogle Scholar
Noyes, RJr, Clarkson, C, Crowe, RR, Yates, WR, McChesney, CM. A family study of generalized anxiety disorder. Am J Psychiatry 1986;144(8):1019–1024. Google ScholarPubMed
Weissman, MM, Wickramaratne, P, Adams, PBet al. The relationship between panic disorder and major depression. A new family study. Arch General Psychiatry 1993;50: 767–780. CrossRefGoogle ScholarPubMed
Hopper, JL, Judd, FK, Derrick, PL, Burrows, GD. A family study of panic disorder. Genet Epidemiol 1987;4: 33–41.CrossRefGoogle ScholarPubMed
Moran, C, Andrews, G. The familial occurrence of agoraphobia. Br J Psychiatry 1985;146: 262–267.CrossRefGoogle ScholarPubMed
Goldstein, RB, Wickramaratne, PJ, Horwath, E, Weissman, MM. Familial aggregation and phenomenology of ‘early’-onset (at or before age 20 years) panic disorder. Arch General Psychiatry 1997;54: 271–278. CrossRefGoogle ScholarPubMed
Horwath, E, Adams, P, Wickramaratne, P, Pine, D, Weissman, MM. Panic disorder with smothering symptoms: evidence for increased risk in first-degree relatives. Depress Anxiety 1997;6: 147–153.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Klerman, GL, Hirschfeld, RM A, Weissmann, MMet al. Panic anxiety and its treatment. Washinton, DC: American Psychiatric Association, 1993. Google Scholar
Knowles, JA, Weissmann, MM. Panic disorder and agaraphobia. In: Oldham, JM, Riba, JM, eds. Review of Psychiatry, vol. 14. Washington, DC: American Psychiatric Association Press, 1995: 383–404.Google Scholar
Hettema, JM, Neale, MC, Kendler, KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 2001;158: 1568–1578.CrossRefGoogle ScholarPubMed
Kendler, KS, Neale, MC, Kessler, RC, Heath, AC, Eaves, LJ. Panic disorder in women: a population-based twin study. Psychol Med 1993;23: 397–406.CrossRefGoogle ScholarPubMed
Perna, G, Caldirola, D, Arancio, C, Bellodi, L. Panic attacks: a twin study. Psychiatry Res 1997;66: 69–71.CrossRefGoogle ScholarPubMed
Torgersen, S. Genetic factors in anxiety disorders. Arch General Psychiatry 1983;40: 1085–1089. CrossRefGoogle ScholarPubMed
Torgersen, S. Comorbidity of major depression and anxiety disorders in twin pairs. Am J Psychiatry 1990;147: 1199–1202.Google ScholarPubMed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 3rd edn. Washington, DC: American Psychiatric Association, 1987. Google ScholarPubMed
Skre, I, Onstad, S, Torgersen, S, Lygren, S, Kringlen, E. A twin study of DSM-III-R anxiety disorders. Acta Psychiatr Scand 1993;88: 85–92.CrossRefGoogle ScholarPubMed
Eysenck, HJ, Eysenck, SB. The orthogonality of psychoticism and neuroticism: a factorial study. Percept Mot Skills 1971;33: 461–462.CrossRefGoogle ScholarPubMed
Andrews, G, Stewart, G, Allen, R, Henderson, AS. The genetics of six neurotic disorders: a twin study. J Affect Disord 1990;19: 23–29.CrossRefGoogle ScholarPubMed
Mannuzza, S, Chapman, TF, Klein, DF, Fyer, AJ. Familial transmission of panic disorder: effect of major depression comorbidity. Anxiety 199495;1(4):180–185.CrossRefGoogle ScholarPubMed
MacKinnon, DF, McMahon, FJ, Simpson, SG, McInnis, MG, Depaulo, JR. Panic disorder with familial bipolar disorder. Biol Psychiatry 1997;42(2):90–95.CrossRefGoogle ScholarPubMed
Noyes, R, Crowe, RR, Harris, EL, Hamra, BJ, McChesney, CM, Chaudhry, DR. Relationship between panic disorder and agoraphobia. A family study. Arch General Psychiatry 1996;43: 227–232. CrossRefGoogle ScholarPubMed
Pauls, DL, Noyes, R, Crowe, RR. The familial prevalence in second-degree relatives of patients with anxiety neurosis (panic disorder). J Affect Disord 1979;1: 279–285.CrossRefGoogle Scholar
Vieland, VJ, Hodge, SE, Lish, JD, Adams, P, Weissmann, MM. Segregation analysis of panic disorder. Psychiatric Genet 1993;3: 63–71. CrossRefGoogle Scholar
Vieland, VJ, Goodman, DW, Chapman, T, Fyer, AJ. New segregation analysis of panic disorder. Am J Med Genet 1996;6: 147–153. 3.0.CO;2-P>CrossRefGoogle Scholar
Knowles, JA, Fyer, AJ, Vieland, VJet al. Results of a genome-wide genetic screen for panic disorder. Am J Med Genet 1998;81: 139–147.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Smoller, JW, Acierno, JS, Rosenbaum, JFet al. Targeted genome screen of panic disorder and anxiety disorder proneness using homology to murine QTL regions. Am J Med Genet 2001;105: 195–206.CrossRefGoogle ScholarPubMed
Crowe, RR, Goedken, R, Samuelson, S, Wilson, R, Nelson, J, Noyes, R. Genomewide survey of panic disorder. Am J Med Genet 2001;105: 105–109.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
Gelernter, J, Bonvicini, K, Page, Get al. Linkage genome scan for loci predisposing to panic disorder or agoraphobia. Am J Med Genet 2001;105: 548–557.CrossRefGoogle ScholarPubMed
Weissman, MM, Fyer, AJ, Haghighi, Fet al. Potential panic disorder syndrome: clinical and genetic linkage evidence. Am J Med Genet 2000;96: 24–35.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Hamilton, SP, Fyer, AJ, Durner, Met al. Further evidence for a panic disorder syndrome mapping to chromosome 13q. Proc Natl Acad Sci USA 2003;100: 2550–2555.CrossRefGoogle ScholarPubMed
Terwilliger, JD, Ott, J. A haplotype-based ‘haplotype relative risk’ approach to detecting allelic associations. Hum Hered 1992;42: 337–346.CrossRefGoogle ScholarPubMed
Bradwejn, J, Koszycki, D. The cholecystokinin hypothesis of anxiety and panic disorder. Ann NY Acad Sci 1994;713: 273–282.CrossRefGoogle ScholarPubMed
Charney, DS, Woods, SW, Goodman, WK, Heninger, GR. Neurobiological mechanisms of panic anxiety. biochemical and behavioral correlates of yohimbine-induced panic attacks. Am J Psychiatry 1987;144: 1030–1036.Google ScholarPubMed
Demontigny, C. Cholecystokinin tetrapeptide induces panic-like attacks in healthy volunteers: preliminary findings. Arch General Psychiatry 1989;46: 511–517. CrossRefGoogle Scholar
Gorman, JM, Papp, LA, Coplan, JDet al. Anxiogenic effects of CO2 and hyperventilation in patients with panic disorder. Am J Psychiatry 1994;151: 547–553.Google ScholarPubMed
Klein, DF. False suffocation alarms, spontaneous panics, and related conditions: An integrative hypothesis. Arch General Psychiatry 1993;50: 306–317. CrossRefGoogle Scholar
Liebowitz, MR, Gorman, JM, Fyer, AJet al. Lactate provocation of panic attacks: II. Biochemical and physiological findings. Arch General Psychiatry 1985;42: 709–719. CrossRefGoogle ScholarPubMed
Perna, G, Gabriele, A, Caldirola, D, Bellodi, L. Hypersensitivity to inhalation of carbon dioxide and panic attacks. Psychiatry Res 1995;57: 267–273.CrossRefGoogle ScholarPubMed
Pitts, FN, McClure, JN. Lactate metabolism in anxiety neurosis. N Engl J Med 1967;227: 1329–1339. CrossRefGoogle Scholar
Woods, SW, Charney, DS, Like, J, Goodman, WK, Redmond, DE, Heninger, GR. Carbon dioxide sensitivity in panic anxiety. Ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment. Arch General Psychiatry 1987;43: 900–909. CrossRefGoogle ScholarPubMed
Sand, PG, Mori, T, Godau, Cet al. Norepinephrine transporter gene (NET) variants in patients with panic disorder. Neurosci Lett 2002;333: 41–44.CrossRefGoogle ScholarPubMed
Uhde, TW, Boulenger, JP, Post, RMet al. Fear and anxiety: relationship to noradrenergic function. Psychopathol 1984;17: 8–23. CrossRefGoogle ScholarPubMed
Charney, DS, Woods, SW, Heninger, GR. Noradrenergic function in generalized anxiety disorder: effects of yohimbine in healthy subjects and patients with generalized anxiety disorder. Psychiatry Res 1989;27(2):173–182.CrossRefGoogle ScholarPubMed
Albus, M, Zahn, TP, Breier, A. Anxiogenic properties of yohimbine. II. Influence of experimental set and setting. Eur Arch Psychiatry Clin Neurosci 1992;241: 345–351.CrossRefGoogle ScholarPubMed
Bylund, DB. Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J 1992;6: 832–839.Google ScholarPubMed
Bylund, DB, Eikenberg, DC, Hieble, JPet al. International Union of Pharmacology nomenclature of adreno- ceptors. Pharmacol Rev 1994;46: 121–136.Google Scholar
Lorenz, W, Lomansney, JW, Collins, S, Regan, JW, Caron, MG, Lefkowitz, RJ. Expression of three alpha2-adrenergic receptor subtypes in rat tissues: implication for alpha2 receptor classification. Mol Pharmacol 1990; 38: 599–603.Google Scholar
Ohara, K, Suzuki, Y, Ochiai, M, Terada, H. Polymorphism in the promoter region of the alpha (2A)-adrenergic receptor gene and panic disorders. Psychiatry Res 2000;93: 79–82.CrossRefGoogle ScholarPubMed
Deckert, J, Nothen, MM, Franke, Pet al. Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease. Mol Psychiatry 1998;3: 81–85.CrossRefGoogle Scholar
Hamilton, SP, Haghighi, F, Heiman, GAet al. Investigation of dopamine receptor (DRD4) and dopamine transporter (DAT) polymorphisms for genetic linkage or association to panic disorder. Am J Med Genet 2000;96: 324–330.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Murphy, DL. Neuropsychiatric disorders and the multiple human brain serotonin receptor subtypes and subsystems. Neuropsychopharmacology 1990;3: 457–471.Google ScholarPubMed
Coplan, JD, Liebowitz, MR, Gorman, JMet al. Noradrenergic function in panic disorder. Effects of intravenous clonidine pretreatment on lactate induced panic. Biol Psychiatry 1992;31: 135–146.CrossRefGoogle ScholarPubMed
Inada, Y, Yoneda, H, Koh, J, Sakai, J, Himei, A, Kinoshita, Yet al. Positive association between panic disorder and polymorphism of the serotonin 2A receptor gene. Psychiatry Res 2003;118: 25–31.CrossRefGoogle ScholarPubMed
Deckert, J, Catalano, M, Heils, Aet al. Functional promoter polymorphism of the human serotonin transporter: lack of association with panic disorder. Psychiatr Genet 1997;7: 45–47.CrossRefGoogle ScholarPubMed
Ishiguro, H, Arinami, T, Yamada, K, Otsuka, Y, Toru, M, Shibuya, H. An association study between a transcriptional polymorphism in the serotonin transporter gene and panic disorder in a Japanese population. Psychiatry Clin Neurosci 1997;51: 333–335.CrossRefGoogle Scholar
Matsushita, S, Muramatsu, T, Kimura, Met al. Serotonin transporter gene regulatory region polymorphism and panic disorder. Mol Psychiatry 1997;2: 390–392.CrossRefGoogle ScholarPubMed
Hamilton, SP, Heiman, GA, Haghighi, Fet al. Lack of genetic linkage or association between a functional serotonin transporter polymorphism and panic disorder. Psychiatr Genet 1999;9: 1–6.CrossRefGoogle ScholarPubMed
Steinlein, OK, Deckert, J, Nothen, MMet al. Neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and panic disorder: an association study. Am J Med Genet 1997;74: 199–201.3.0.CO;2-D>CrossRefGoogle Scholar
Deckert, J, Catalano, M, Syagailo, YVet al. Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet 1999;8: 621–624.CrossRefGoogle ScholarPubMed
Hamilton, SP, Slager, SL, Heiman, GAet al. No genetic linkage or association between a functional promoter polymorphism in the monoamine oxidase-A gene and panic disorder. Mol Psychiatry 2000;5: 465–466.CrossRefGoogle ScholarPubMed
Hamilton, SP, Slager, SL, Heiman, GAet al. Evidence for a susceptibility locus for panic disorder near the catechol-O-methyltransferase gene on chromosome 22. Biol Psychiatry 2002;51: 591–601.CrossRefGoogle ScholarPubMed
Woo, JM, Yoon, KS, YuBh, . Catechol O-methyltransferase genetic polymorphism in panic disorder. Am J Psychiatry 2002;159: 1785–1787.CrossRefGoogle ScholarPubMed
Craddock, N, Dave, S, Greening, J. Association studies of bipolar disorder. Bipolar Disord 2001;3(6):284–298.CrossRefGoogle ScholarPubMed
Zorumski, CF, Eisenberg, KE. Insights into the structure and function of GABA-benzodiazepine receptors: ion channels and psychiatry. Am J Psychiatry 1991;148: 162–173.Google ScholarPubMed
Crowe, RR, Noyes, R, Wang, Z, Albrecht, BE, Darlison, MG, Bailey, MEet al. Candidate gene study of eight GABAA receptor subunits in panic disorder. Am J Psychiatry 1997;154: 1096–1100.Google ScholarPubMed
Bradwejn, J, Koszycki, D, Shriqui, C. Enhanced sensitivity to cholecystokinin tetrapeptide in panic disorder. Clinical and behavioral findings. Arch General Psychiatry 1991;48: 603–610. CrossRefGoogle ScholarPubMed
Bradwejn, J, Koszycki, D, Payeur, R, Bourin, M, Borhwick, H. Replication of action of cholecystokinin tetrapeptide in panic disorder: clinical and behavioral findings. Am J Psychiatry 1992;149: 962–964.Google ScholarPubMed
van Megen, HJ, Westenberg, HG, Den Boer, JA, Kahn, RS. Cholecystokinin in anxiety. Eur Neuropsychopharmacol 1996;6: 263–280.CrossRefGoogle ScholarPubMed
Kennedy, JL, Bradwejn, J, Koszycki, Det al. Investigation of cholecystokinin system genes in panic disorder. Mol Psychiatry 1999;4: 284–285.CrossRefGoogle ScholarPubMed
Hamilton, SP, Slager, SL, Helleby, Let al. No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorder. Mol Psychiatry 2001;6: 59–65.CrossRefGoogle ScholarPubMed
Hattori, E, Yamada, K, Toyota, Tet al. Association studies of the CT repeat polymorphism in the 5′ upstream region of the cholecystokinin B receptor gene with panic disorder and schizophrenia in Japanese subjects. Am J Med Genet 2001;105: 779–782.CrossRefGoogle Scholar
Yamada, K, Hattori, E, Shimizu, M, Sugaya, A, Shibuya, H, Yoshikawa, T. Association studies of the cholecystokinin B receptor and A2a adenosine receptor genes in panic disorder. J Neural Transm 2001;108: 837–848.CrossRefGoogle ScholarPubMed
Hattori, E, Ebihara, M, Yamada, K, Ohba, H, Shibuya, H, Yoshikawa, T. Identification of a compound short tandem repeat stretch in the 5′- upstream region of the cholecystokinin gene, and its association with panic disorder but not with schizophrenia. Mol Psychiatry 2001; 6: 465–470.CrossRefGoogle Scholar
Ebihara, M, Ohba, H, Hattori, E, Yamada, K, Yoshikawa, T. Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility. Am J Med Genet 2003;118B: 32–35.CrossRefGoogle ScholarPubMed
Wang, Z, Valdes, J, Noyes, R, Zoega, T, Crowe, RR. Possible association of a cholecystokinin promotor polymorphism (CCK- 36CT) with panic disorder. Am J Med Genet 1998;81: 228–234.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Comings, DE, Muhleman, D, Johnson, P, MacMurray, JP. Potential role of the estrogen receptor gene (ESR1) in anxiety. Mol Psychiatry 1999;4: 374–377.CrossRefGoogle Scholar
Sand, PG, Schlurmann, K, Luckhaus, Cet al. Estrogen receptor 1 gene (ESR1) variants in panic disorder. Am J Med Genet 2002;114: 426–428.CrossRefGoogle ScholarPubMed
Kelly, MJ, Levin, ER. Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol Metab 2001;12: 152–156.CrossRefGoogle ScholarPubMed
Gratacos, M, Nadal, M, Martin-Santos, Ret al. A Polymorphic genomic duplication on human chromosome 15 is a susceptibility factor to panic and phobic disorders. Cell 2001;106: 367–379.CrossRefGoogle ScholarPubMed
Armengol, L, Gratacos, M, Pujana, MA, Ribases, M, Martin-Santos, R, Estivill, X. 5′UTR-region SNP in the NTRK3 gene is associated with panic disorder. Mol Psychiatry 2002;7: 928–930.CrossRefGoogle Scholar
Tabiner, M, Youings, S, Dennis, Net al. Failure to find DUP25 in patients with anxiety disorders in control individuals, or in previously reported positive control cell lines. Am J Hum Genet 2003;72: 535–538.CrossRefGoogle ScholarPubMed
Scherrer, JF, True, WR, Xian, Het al. Evidence for genetic influences common and specific to symptoms of generalized anxiety and panic. J Affect Disord 2000; 57: 25–35.CrossRefGoogle ScholarPubMed
Ohara, K, Nagai, M, Suzuki, Y, Ochiai, M, Ohara, K. No association between anxiety disorders and catechol-O- methyltransferase polymorphism. Psychiatry Res 1998; 80: 145–148.CrossRefGoogle ScholarPubMed
Tadic, A, Rujescu, D, Szegedi, Aet al. Association of a MAOA gene variant with generalized anxiety disorder, but not with panic disorder or major depression. Am J Med Genet 2003;117B: 1–6.CrossRefGoogle ScholarPubMed
Fehr, C, Szegedi, A, Anghelescu, I, Klawe, C, Hiemke, C, Dahmen, N. Sex differences in allelic frequencies of the 5-HT2C Cys23Ser polymorphism in psychiatric patients and healthy volunteers: findings from an association study. Psychiatr Genet 2000;10: 59–65.CrossRefGoogle ScholarPubMed
Deckert, J, Meyer, J, Catalano, Met al. Novel 5′-regulatory region polymorphisms of the 5-HT2C receptor gene: association study with panic disorder. Int J Neuropsychopharmacol 2000;3: 321–325.CrossRefGoogle ScholarPubMed
Ise, K, Akiyoshi, J, Horinouchi, Y, Tsutsumi, T, Isogawa, K, Nagayama, H. Association between the CCK-A receptor gene and panic disorder. Am J Med Genet 2003;118B: 29–31.CrossRefGoogle ScholarPubMed
Sand, PG, Godau, C, Riederer, Pet al. Exonic variants of the GABA (B) receptor gene and panic disorder. Psychiatry Genet 2000;10: 191–194. CrossRefGoogle ScholarPubMed