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BMC Psychiatry

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Open Access 01-12-2008 | Research article

Depression and anxiety in relation to catechol-O-methyltransferase Val¹⁵⁸Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT)

Authors: Petter M Bækken, Frank Skorpen, Eystein Stordal, John-Anker Zwart, Knut Hagen

Published in: BMC Psychiatry | Issue 1/2008

Abstract

Background

The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. The aim of the present study was to examine the relationship between the Val158Met COMT gene polymorphism and anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) in the general adult population.

Methods

In the Nord-Trøndelag Health Study (HUNT) the association between the Val158Met polymorphism and anxiety and depression was evaluated in a random sample of 5531 individuals. Two different cut off scores (≥ 8 and ≥ 11) were used to identify cases with anxiety (HADS-A) and depression (HADS-D), whereas controls had HADS-A <8 and HADS-D <8.

Results

The COMT genotype distribution was similar between controls and individuals in the groups with anxiety and depression using cut-off scores of ≥ 8. When utilizing the alternative cut-off score HADS-D ≥ 11, Met/Met genotype and Met allele were less common among men with depression compared to the controls (genotype: p = 0.017, allele: p = 0.006). In the multivariate analysis, adjusting for age and heart disease, depression (HADS-D ≥ 11) was less likely among men with the Met/Met genotype than among men with the Val/Val genotype (OR = 0.37, 95% CI = 0.18–0.76).

Conclusion

In this population-based study, no clear association between the Val158Met polymorphism and depression and anxiety was revealed. The Met/Met genotype was less likely among men with depression defined as HADS-D ≥ 11, but this may be an incidental finding.

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Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melén K, Julkunen I, Taskinen J: Kinetics of human soluble and membrane-bound catechol-O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry. 1995, 34: 4202-10. 10.1021/bi00013a008.CrossRefPubMed

Craddock N, Owen MJ, O'Donovan MC: The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol Psychiatry. 2006, 11: 446-458. 10.1038/sj.mp.4001808.CrossRefPubMed

Massat I, Souery D, Del-Favero J, Nothen M, Blackwood D, Muir W, Kaneva R, Serretti A, Lorenzi C, Rietschel M, Milanova V, Papadimitriou GN, Dikeos D, Van Broekhoven C, Mendlewicz : Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. Mol Psychiatry. 2005, 10: 598-605. 10.1038/sj.mp.4001615.CrossRefPubMed

Ohara K, Nagai M, Suzuki Y, Ohara K: Low activity allele of the catechol-o-methyltransferase gene and Japanese unipolar depression. Neuroreport. 1998, 9: 1305-1308.CrossRefPubMed

Rothe C, Koszycki D, Bradwejn J, King N, Deluca V, Tharmalingam S, Macciardi F, Deckert J, Kennedy JL: Association of the Val158Met catechol-O-methyltransferase genetic polymorphism with panic disorder. Neuropsychopharmacology. 2006, 31: 2237-2242.PubMed

Samochowiec J, Hajduk A, Samochowiec A, Horodnicki J, Stepien G, Grzywacz A, Kucharska-Mazur J: Association of MAO-A, COMT, and 5-HTT genes polymorphisms in patients with anxiety disorders of the phobic spectrum. Psychiatry Res. 2004, 128: 21-26. 10.1016/j.psychres.2004.05.012.CrossRefPubMed

Woo JN, Yoon KS, Choi YH, Oh KS, Lee YS, Yu BH: The association between panic disorder and the L/L genotype of catechol-O-methyltransferase. J Psychiatr Res. 2004, 38: 365-370. 10.1016/j.jpsychires.2004.01.001.CrossRefPubMed

Domschke K, Deckert J, O'Donovan MC, Glatt SJ: Meta-Analysis of COMT val158met in Panic Disorder: Ethnic Heterogeneity and Gender Specificity. Am J Med Genet B Neuropsychiatr Genet. 2007, 144B (5): 667-73. 10.1002/ajmg.b.30494.CrossRefPubMed

Spinhoven PH, Ormel J, Sloekers PP, Kempen GI, Speckens AE, Van Hemert AM: A validation study of the Hospital anxiety and depression scale (HADS) in different groups of Dutch subjects. Psychol Med. 1997, 27: 363-370. 10.1017/S0033291796004382.CrossRefPubMed

10.

Hermann C: International experiences with the Hospital and depression scale: A review of validation data and clinical results. J Psychosom Res. 1997, 42: 17-41. 10.1016/S0022-3999(96)00216-4.CrossRef

11.

Bjelland I, Dahl AA, Haug TT, Neckelman D: The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002, 52: 69-77. 10.1016/S0022-3999(01)00296-3.CrossRefPubMed

12.

Aylard PR, Gooding JH, McKenna PJ, Snaith RP: A validation study of three anxiety and depression self-assessment scales. J Psychosom Res. 1987, 31: 261-268. 10.1016/0022-3999(87)90083-3.CrossRefPubMed

13.

Lewis G, Wessely S: Comparison of the General Health Questionnaire and the Hospital Anxiety and Depression Scale. Br J Psychiatry. 1990, 157: 860-864.CrossRefPubMed

14.

Watson D, Weber K, Assenheimer JS, Clark LA, Strauss ME, McCormick RA: Testing a tripartite model: I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales. J Abnorm Psychol. 1995, 104: 3-14. 10.1037/0021-843X.104.1.3.CrossRefPubMed

15.

Lisspers J, Nygren A, Söderman E: Hospital Anxiety and Depression Scale (HAD): some psychometric data for a Swedish sample. Acta Psychiatr Scand. 1997, 96: 281-286. 10.1111/j.1600-0447.1997.tb10164.x.CrossRefPubMed

16.

Holmen J, Midthjell K, Krüger Ø, Langhammer A, Holmen TL, Bratberg GH, Vatten L, Lund-Larsen PG: The Nord-Trøndelag Health Study 1995–97 (HUNT 2): Objectives, contents, methods and participation. Norsk Epidemiologi. 2003, 13: 19-32.

17.

Holmen J, Midthjell K, Forsèn L, Skjerve K, Gorseth M, Oseland A: A health survey in Nord-Trøndelag 1984–86. Participation and comparison of attendants and non-attendants. Tidsskr Nor Laegeforen. 1990, 110: 1973-1977.PubMed

18.

Hagen K, Pettersen E, Stovner LJ, Skorpen F, Holmen J, Zwart JA: High systolic blood pressure is associated with Val/Val genotype in the catechol-o-methyltransferase gene. Am J Hypertens. 2007, 20: 21-26. 10.1016/j.amjhyper.2006.05.023.CrossRefPubMed

19.

Wittwer CT, Ririe KM, Andrew RV, David DA, Gundry RA, Balis UJ: The LightCycler: a microvolume multisample fluorimeter with rapid temperature control. Biotechniques. 1997, 22: 176-181.PubMed

20.

Stordal E, Krüger MB, Dahl NH, Krüger Ø, Mykletun A, Dahl AA: Depression in relation to age and gender in the general population: the Nord-Trøndelag Health Study (HUNT). Acta Psychiatr Scand. 2001, 104: 210-216. 10.1034/j.1600-0447.2001.00130.x.CrossRefPubMed

21.

Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983, 67: 361-370. 10.1111/j.1600-0447.1983.tb09716.x.CrossRefPubMed

22.

Stordal E, Mykletun A, Dahl AA: The association between age and depression in the general population: a multivariate examination. Acta Psychiatr Scand. 2003, 107: 132-141. 10.1034/j.1600-0447.2003.02056.x.CrossRefPubMed

23.

Palmatier MA, Kang AM, Kidd KK: Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles. Biol Psychiatry. 1999, 46: 557-567. 10.1016/S0006-3223(99)00098-0.CrossRefPubMed

24.

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. 10.1016/S0165-1781(98)00062-6.CrossRefPubMed

25.

McGrath M, Kawachi I, Ascherio A, Colditz GA, Hunter DJ, De Vivo I: Association between catechol-O-methyltransferase and phobic anxiety. Am J Psychiatry. 2004, 161: 1703-1705. 10.1176/appi.ajp.161.9.1703.CrossRefPubMed

26.

Domschke K, Freitag CM, Kuhlenbaumer G, Schirmacher A, Sand P, Nyhuis P, Jacob C, Fritze J, Franke P, Rietschel M, Garritsen HS, Fimmers R, Nothen MM, Lesch KP, Stogbauer F, Deckert J: Association of the functional V158M catechol-O-methyltransferase polymorphism with panic disorder in women. Int J Neuropsychopharmacol. 2004, 7: 183-188. 10.1017/S146114570400416X.CrossRefPubMed

27.

Freitag CM, Domschke K, Rothe C, Lee YJ, Hohoff C, Gutknecht L, Sand P, Fimmers R, Lesch KP, Deckert J: Interaction of serotonergic and noradrenergic gene variants in panic disorder. Psychiatr Genet. 2006, 16: 59-65. 10.1097/01.ypg.0000199443.69668.b1.CrossRefPubMed

28.

Hansen V, Jacobsen K, Arnesen E: Prevalence of Serious Psychiatric Morbidity in Attenders and Nonattenders to a Health Survey of a General Population. Am J Epidemiol. 2001, 154: 891-894. 10.1093/aje/154.10.891.CrossRefPubMed

29.

Mykletun A, Stordal E, Dahl AA: The Hospital Anxiety and Depression (HAD) scale: factor structure, item analyses, and internal consistency in a large population. Br J Psychiatry. 2001, 179: 540-544. 10.1192/bjp.179.6.540.CrossRefPubMed

30.

Zwart JA, Dyb G, Hagen K, Dahl AA, Ødegård KJ, Bovim G, Stovner LJ: Depression and anxiety disorders associated with headache frequency. The Nord-Trøndelag Health Study. Eur J Neurol. 2003, 10: 147-152. 10.1046/j.1468-1331.2003.00551.x.CrossRefPubMed

31.

Oedegaard KJ, Neckelmann D, Mykletun A, Dahl AA, Zwart JA, Hagen K, Fasmer OB: Migraine with and without aura: Association with depression and anxiety disorder in a population-based study. The HUNT Study. Cephalalgia. 2006, 26: 1-6. 10.1111/j.1468-2982.2005.00974.x.CrossRefPubMed

32.

Kunugi H, Vallada HP, Hoda F, Kirov G, Gill M, Aitchison KJ, Arranz MJ, Murray RM, Collier DA: No evidence for an association of affective disorders with high- or low-activity allele of catechol-o-methyltransferase gene. Biol Psychiatry. 1997, 42: 282-285. 10.1016/S0006-3223(96)00366-6.CrossRefPubMed

33.

Frisch A, Postilnick D, Rockah R, Michaelovsky E, Postilnick S, Birman E, Laor N, Rauchverger B, Kreinin A, Poyurovsky M, Schneidman B, Modai I, Weizman R: Association of unipolar major depressive disorder with genes of the seretonergic and dopaminergic pathways. Mol Psychiatry. 1999, 4: 389-392. 10.1038/sj.mp.4000536.CrossRefPubMed

34.

Jabbi M, Kema IP, Pompe van der G, te Meerman GJ, Ormel J, den Boer JA: Catechol-o-methyltransferase polymorphism and susceptibility to major depressive disorder modulates psychological stress response. Psychiatr Genet. 2007, 17: 183-193. 10.1097/YPG.0b013e32808374df.CrossRefPubMed

35.

Wichers M, Aguilera M, Kenis G, Krabbendam L, Myin-Germeys I, Jacobs N, Peeters F, Derom C, Vlietinck R, Mengelers R, Delespaul P, van Os J: The Catechol-O-Methyltransferase Val158Met Polymorphism and Experience of Reward in the Flow of Daily Life. Neuropsychopharmacology. 2007,

36.

Enoch MA, Xu K, Ferro E, Harris CR, Goldman D: Genetic origins of anxiety in women: a role for a functional catechol-O-methyltransferase polymorphism. Psychiatr Genet. 2003, 13: 33-41. 10.1097/00041444-200303000-00006.CrossRefPubMed

37.

Martin CR: What does the Hospital anxiety and depression scale (HADS) really measure in liaison psychiatry settings?. Curr Psychiatry Rev. 2005, 1: 69-73. 10.2174/1573400052953510.CrossRef

38.

Hamilton SP, Slager SL, Heiman GA, Deng Z, Haghighi F, Klein DF, Hodge SE, Weissman MM, Fyer AJ, Knowles JA: Evidence for a susceptibility locus for panic disorder near the catechol-O-methyltransferase gene on chromosome 22. Biol Psychiatry. 2002, 51: 591-601. 10.1016/S0006-3223(01)01322-1.CrossRefPubMed

39.

Funke B, Malhotra AK, Finn CT, Plocik AM, Lake SL, Lencz T, DeRosse P, Kane JM, Kucherlapati R: COMT genetic variation confers risk for psychotic and affective disorders: a case control study. Behav Brain Funct. 2005, 1: 19-10.1186/1744-9081-1-19.CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/8/48/prepub

Title: Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT)
Authors: Petter M Bækken
Frank Skorpen
Eystein Stordal
John-Anker Zwart
Knut Hagen
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: BMC Psychiatry / Issue 1/2008
Electronic ISSN: 1471-244X
DOI: https://doi.org/10.1186/1471-244X-8-48

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Depression and anxiety in relation to catechol-O-methyltransferase Val¹⁵⁸Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT)

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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