What is the genetic relationship between anxiety and depression?

American Journal of Medical Genetics, Part C: Seminars in Medical Genetics

Volumn 148, Issue 2, 2008, Pages 140-146

  Hettema, John M ^a,b,c  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b VCU Anxiety Disorders Specialty Clinic

^c VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Anxiety disorders; Genetics; Major depression

Indexed keywords

ALCOHOLISM; ANTISOCIAL BEHAVIOR; ANXIETY DISORDER; CHROMOSOME 1; CHROMOSOME 11; CHROMOSOME 12; CHROMOSOME 15; CHROMOSOME 3; COMORBIDITY; CONDUCT DISORDER; DEPRESSION; DRUG DEPENDENCE; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HEREDITY; HUMAN; MAJOR DEPRESSION; MOLECULAR GENETICS; MOLECULAR PHYLOGENY; PERSONALITY; PHENOTYPE; PRIORITY JOURNAL; REVIEW;

ANXIETY DISORDERS; DEPRESSIVE DISORDER; DEPRESSIVE DISORDER, MAJOR; FAMILY CHARACTERISTICS; FEMALE; HUMANS; LINKAGE (GENETICS); MALE; MOLECULAR BIOLOGY; PERSONALITY; PHENOTYPE; RISK FACTORS; TWIN STUDIES AS TOPIC;

EID: 43949111673     PISSN: 15524868     EISSN: 15524876     Source Type: Journal    
DOI: 10.1002/ajmg.c.30171     Document Type: Review

References (92)

1. Andrews G, Stewart G, Morris-Yates A, Holt P, Henderson S. 1990. Evidence for a general neurotic syndrome. Br J Psychiatry 157:6-12.
2. Anguelova M, Benkelfat C, Turecki G. 2003. A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders. Mol Psychiatry 8:574-591.
3. Bienvenu OJ, Brown C, Samuels JF, Liang KY, Costa PT, Eaton WW, Nestadt G. 2001. Normal personality traits and comorbidity among phobic, panic and major depressive disorders. Psychiatry Res 102:73-85.
4. Black DW, Noyes R, Jr., Goldstein RB, Blum N. 1992. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 49:362-368.
5. Blaya C, Salum GA, Lima MS, Leistner-Segal S, Manfro GG. 2007. Lack of association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Panic Disorder: A systematic review and meta-analysis. Behav Brain Funct 3:41.
6. Boomsma DI, Beem AL, van den BM, Dolan CV, Koopmans JR, Vink JM, De Geus EJ, Slagboom PE. 2000. Netherlands twin family study of anxious depression (NETSAD). Twin Res 3:323-334.
7. Breslau N, Davis GC, Andreski P, Peterson E. 1991. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 48:216-222.
8. Camp NJ, Lowry MR, Richards RL, Plenk AM, Carter C, Hensel CH, Abkevich V, Skolnick MH, Shattuck D, Rowe KG, Hughes DC, Cannon-Albright LA. 2005. Genome-wide linkage analyses of extended Utah pedigrees identifies loci that influence recurrent, early-onset major depression and anxiety disorders. Am J Med Genet Part B Neuropsychiatr Genet 135B:85-93.
9. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R. 2003. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science 301:386-389.
10. Chantarujikapong SI, Scherrer JF, Xian H, Eisen SA, Lyons MJ, Goldberg J, Tsuang M, True WR. 2001. A twin study of generalized anxiety disorder symptoms, panic disorder symptoms and post-traumatic stress disorder in men. Psychiatry Res 103:133-145.
11. Cox BJ, Clara IP, Enns MW. 2002. Posttraumatic stress disorder and the structure of common mental disorders. Depress Anxiety 15:168-171.
12. Craddock N, Owen MJ, O'donovan MC. 2006. The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: Evidence and lessons. Mol Psychiatry 11:446-458.
13. Davidson JR, Tupler LA, Wilson WH, Connor KM. 1998. A family study of chronic posttraumatic stress disorder following rape trauma. J Psychiatr Res 32:301-309.
14. Dierker LC, Merikangas KR. 2001. Familial psychiatric illness and posttraumatic stress disorder: Findings from a family study of substance abuse and anxiety disorders. J Clin Psychiatry 62:715-720.
15. Domschke K, Deckert J, O'donovan MC, Glatt SJ. 2007. Meta-analysis of COMT val158met in panic disorder: Ethnic heterogeneity and gender specificity. Am J Med Genet Part B Neuropsychiatr Genet 144B:667-673.
16. Eley TC, Tahir E, Angleitner A, Harriss K, McClay J, Plomin R, Riemann R, Spinath F, Craig I. 2003. Association analysis of MAOA and COMT with neuroticism assessed by peers. Am J Med Genet Part B Neuropsychiatr Genet 120B:90-96.
17. Eley TC, Sugden K, Corsico A, Gregory AM, Sham P, McGuffin P, Plomin R, Craig IW. 2004. Gene-environment interaction analysis of serotonin system markers with adolescent depression. Mol Psychiatry 9:908-915.
18. Enoch MA, Kaye WH, Rotondo A, Greenberg BD, Murphy DL, Goldman D. 1998. 5-HT2A promoter polymorphism - 1438G/A, anorexia nervosa, and obsessive-compulsive disorder [letter]. Lancet 351:1785-1786.
19. Enoch MA, Greenberg BD, Murphy DL, Goldman D. 2001. Sexually dimorphic relationship of a 5-HT2A promoter polymorphism with obsessive-compulsive disorder. Biol Psychiatry 49:385-388.
20. Enoch MA, Xu K, Ferro E, Harris CR, Goldman D. 2003. Genetic origins of anxiety in women: A role for a functional catechol-O-methyltransferase polymorphism. Psychiatr Genet 13:33-41.
21. Fanous A, Gardner CO, Prescott CA, Cancro R, Kendler KS. 2002. Neuroticism, major depression and gender: A population-based twin study. Psychol Med 32:719-728.
22. Frisch A, Postilnick D, Rockah R, Michaelovsky E, Postilnick S, Birman E, Laor N, Rauchverger B, Kreinin A, Poyurovsky M, Schneidman M, Modai I, Weizman R. 1999. Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways. Mol Psychiatry 4:389-392.
23. Fullerton J. 2006. New approaches to the genetic analysis of neuroticism and anxiety. Behav Genet 36:147-161.
24. Gelernter J, Bonvicini K, Page G, Woods SW, Goddard AW, Kruger S, Pauls DL, Goodson S. 2001. Linkage genome scan for loci predisposing to panic disorder or agoraphobia. Am J Med Genet 105:548-557.
25. Gizatullin R, Zaboli G, Jonsson EG, Asberg M, Leopardi R. 2005. Haplotype Analysis reveals tryptophan hydroxylase (TPH) 1 gene variants associated with major depression. Biol Psychiatry 59:295-300.
26. Hall D, Dhilla A, Charalambous A, Gogos JA, Karayiorgou M. 2003. Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder. Am J Hum Genet 73:370-376.
27. Henderson AS, Korten AE, Jorm AF, Jacomb PA, Christensen H, Rodgers B, Tan X, Easteal S. 2000. COMT and DRD3 polymorphisms, environmental exposures, and personality traits related to common mental disorders. Am J Med Genet 96:102-107.
28. Hettema JM, Neale MC, Kendler KS. 2001. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 158:1568-1578.
29. Hettema JM, Prescott CA, Kendler KS. 2004. Genetic and environmental sources of covariation between generalized anxiety disorder and neuroticism. Am J Psychiatry 161:1581-1587.
30. Hettema JM, An SS, Neale MC, Bukszar J, van den Oord EJ, Kendler KS, Chen X. 2006a. Association between glutamic acid decarboxylase genes and anxiety disorders, major depression, and neuroticism. Mol Psychiatry 11:752-762.
31. Hettema JM, Neale MC, Myers JM, Prescott CA, Kendler KS. 2006b. A population-based twin study of the relationship between neuroticism and internalizing disorders. Am J Psychiatry 163:857-864.
32. Hettema JM, An SS, Neale MC, Bukszar J, van den Oord EJ, Kendler KS, Chen X. 2008. COMT contributes to genetic susceptibility shared among anxiety spectrum phenotypes. Mol Psychiatry (in press).
33. Horwath E, Wolk SI, Goldstein RB, Wickramaratne P, Sobin C, Adams P, Lish JD, Weissman MM. 1995. Is the comorbidity between social phobia and panic disorder due to familial cotransmission or other factors? Arch Gen Psychiatry 52:574-582.
34. Inada Y, Yoneda H, Koh J, Sakai J, Himei A, Kinoshita Y, Akabame K, Hiraoka Y, Sakai T. 2003. Positive association between panic disorder and polymorphism of the serotonin 2A receptor gene. Psychiatry Res 118:25-31.
35. Jardine R, Martin NG, Henderson AS. 1984. Genetic covariation between neuroticism and the symptoms of anxiety and depression. Genet Epidemiol 1:89-107.
36. Kaabi B, Gelernter J, Woods SW, Goddard A, Page GP, Elston RC. 2006. Genome scan for loci predisposing to anxiety disorders using a novel multivariate approach: Strong evidence for a chromosome 4 risk locus. Am J Hum Genet 78:543-553.
37. Kendler KS. 1993. Twin studies of psychiatric illness: Current status and future directions. Arch Gen Psychiatry 50:905-915.
38. Kendler KS. 1996. Major depression and generalised anxiety disorder, (partly) different environments - Revisited. Br J Psychiatry 168:68-75.
39. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ. 1992. Major depression and generalized anxiety disorder. Same genes, (partly) different environments? Arch Gen Psychiatry 49:716-722.
40. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ. 1993. Major depression and phobias: The genetic and environmental sources of comorbidity. Psychol Med 23:361-371.
41. Kendler KS, Davis CG, Kessler RC. 1997. The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: A family history study. Br J Psychiatry 170:541-548.
42. Kendler KS, Prescott CA, Myers J, Neale MC. 2003. The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Arch Gen Psychiatry 60:929-937.
43. Kendler KS, Kuhn JW, Vittum J, Prescott CA, Riley B. 2005. The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: A replication. Arch Gen Psychiatry 62:529-535.
44. Kendler KS, Gardner CO, Gatz M, Pedersen NL. 2006. The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample. Psychol Med 37:453-462.
45. Kessler RC, Nelson CB, McGonagle KA, Liu J, Swartz M, Blazer DG. 1996. Comorbidity of DSM-III-R major depressive disorder in the general population: Results from the US National Comorbidity Survey. Br J Psychiatry Suppl 168:17-30.
46. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. 2005. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:617-627.
47. Khan AA, Jacobson KC, Gardner CO, Prescott CA, Kendler KS. 2005. Personality and comorbidity of common psychiatric disorders. Br J Psychiatry 186:190-196.
48. Kirk KM, Birley AJ, Statham DJ, Haddon B, Lake RI, Andrews JG, Martin NG. 2000. Anxiety and depression in twin and sib pairs extremely discordant and concordant for neuroticism: Prodromus to a linkage study. Twin Res 3:299-309.
49. Klein DN, Lewinsohn PM, Rohde P, Seeley JR, Shankman SA. 2003. Family study of comorbidity between major depressive disorder and anxiety disorders. Psychol Med 33:703-714.
50. Koenen KC, Lyons MJ, Goldberg J, Simpson J, Williams WM, Toomey R, Eisen SA, True WR, Cloitre M, Wolfe J, Tsuang MT. 2003. A high risk twin study of combat-related PTSD comorbidity. Twin Res 6:218-226.
51. Krueger RF. 1999. The structure of common mental disorders. Arch Gen Psychiatry 56:921-926.
52. Kunugi H, Vallada HP, Hoda F, Kirov G, Gill M, Aitchison KJ, Ball D, Arranz MJ, Murray RM, Collier DA. 1997. No evidence for an association of affective disorders with high-or low-activity allele of catechol -O-methyltransferase gene. Biol Psychiatry 42:282-285.
53. Lasky-Su JA, Faraone SV, Glatt SJ, Tsuang MT. 2005. Meta-analysis of the association between two polymorphisms in the serotonin transporter gene and affective disorders. Am J Med Genet Part B Neuropsychiatr Genet 133B:110-115.
54. Li D, He L. 2007. Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior. Mol Psychiatry 12:47-54.
55. Lin PY. 2007. Meta-analysis of the association of serotonin transporter gene polymorphism with obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 31:683-689.
56. Lin PY, Tsai G. 2004. Association between serotonin transporter gene promoter polymorphism and suicide: Results of a meta-analysis. Biol Psychiatry 55:1023-1030.
57. Lotrich FE, Pollock BG. 2004. Meta-analysis of serotonin transporter polymorphisms and affective disorders. Psychiatr Genet 14:121-129.
58. MacKinnon DF, Xu J, McMahon FJ, Simpson SG, Stine OC, McInnis MG, DePaulo JR. 1998. Bipolar disorder and panic disorder in families: An analysis of chromosome 18 data. Am J Psychiatry 155:829-831.
59. Maier W, Lichtermann D, Minges J, Oehrlein A, Franke P. 1993. A controlled family study in panic disorder. J Psychiatr Res 27:79-87.
60. Maser JD, Cloninger CR. 1990. Comorbidity of Mood and Anxiety Disorders. In: Maser JD, Cloninger CR, editors. Washington, DC: American Psychiatric Press.
61. 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 J. 2005. Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. Mol Psychiatry 10:598-605.
62. McGrath M, Kawachi I, Ascherio A, Colditz GA, Hunter DJ, De VI. 2004. Association between catechol-O-methyltransferase and phobic anxiety. Am J Psychiatry 161:1703-1705.
63. Mendlewicz J, Papadimitriou GN, Wilmotte J. 1993. Family study of panic disorder: Comparison with generalized anxiety disorder, major depression and normal subjects. Psychiatr Genet 3:73-78.
64. Middeldorp CM, Cath DC, Van Dyck R, Boomsma DI. 2005. The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies. Psychol Med 35:611-624.
65. Nash MW, Huezo-Diaz P, Williamson RJ, Sterne A, Purcell S, Hoda F, Cherny SS, Abecasis GR, Prince M, Gray JA, Ball D, Asherson P, Mann A, Goldberg D, McGuffin P, Farmer A, Plomin R, Craig IW, Sham PC. 2004. Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships. Hum Mol Genet 13:2173-2182.
66. Nash MW, Sugden K, Huezo-Diaz P, Williamson R, Sterne A, Purcell S, Sham PC, Craig IW. 2005. Association analysis of monoamine genes with measures of depression and anxiety in a selected community sample of siblings. Am J Med Genet Part B Neuropsychiatr Genet 135B:33-37.
67. Neale MC, Cardon LR. 1992. Methodology for genetic studies of twins and families. Dordrecht, The Netherlands: Kluwer Academic Publishers B.V.
68. Neale BM, Sullivan PF, Kendler KS. 2005. A genome scan of neuroticism in nicotine dependent smokers. Am J Med Genet Part B Neuropsychiatr Genet 132B:65-69.
69. Nelson EC, Grant JD, Bucholz KK, Glowinski A, Madden PAF, Reich W, Heath AC. 2000. Social phobia in a population-based female adolescent twin sample: Co- morbidity and associated suicide-related symptoms [in process citation]. Psychol Med 30:797-804.
70. Nestadt G, Samuels J, Riddle MA, Liang KY, Bienvenu OJ, Hoehn-Saric R, Grados M, Cullen B. 2001. The relationship between obsessive-compulsive disorder and anxiety and affective disorders: Results from the Johns Hopkins OCD Family Study. Psychol Med 31:481-487.
71. Noyes R, Crowe RR, Harris EL, Hamra BJ, McChesney CM, Chaudhry DR. 1986. Relationship between panic disorder and agoraphobia. Arch Gen Psychiatry 43:227-232.
72. Ohara K, Nagai M, Suzuki Y, Ohara K. 1998. Low activity allele of catechol-o-methyltransferase gene and Japanese unipolar depression. Neuroreport 9:1305-1308.
73. Olsson CA, Anney RJ, Lotfi-Miri M, Byrnes GB, Williamson R, Patton GC. 2005. Association between the COMT Val158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health. Psychiatr Genet 15:109-115.
74. Pooley EC, Fineberg N, Harrison PJ. 2007. The met(158) allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: Case-control study and meta-analysis. Mol Psychiatry 12:556-561.
75. Regier DA, Rae DS, Narrow WE, Kaelber CT, Schatzberg AF. 1998. Prevalence of anxiety disorders and their comorbidity with mood and addictive disorders. Br J Psychiatry Suppl 173:24-28.
76. Reich J. 1995. Family psychiatric histories in male patients with generalized anxiety disorder and major depressive disorder. Ann Clin Psychiatry 7:71-78.
77. Roy M-A, Neale MC, Pedersen NL, Mathe AA, Kendler KS. 1995. A twin study of generalized anxiety disorder and major depression. Psychol Med 25:1037-1049.
78. Scherrer JF, True WR, Xian H, Lyons MJ, Eisen SA, Goldberg J, Lin N, Tsuang MT. 2000. Evidence for genetic influences common and specific to symptoms of generalized anxiety and panic. J Affect Disord 57:25-35.
79. Schinka JA, Busch RM, Robichaux-Keene N. 2004. A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Mol Psychiatry 9:197-202.
80. Schumacher J, Jamra RA, Becker T, Ohlraun S, Klopp N, Binder EB, Schulze TG, Deschner M, Schmal C, Hofels S, Zobel A, Illig T, Propping P, Holsboer F, Rietschel M, Nothen MM, Cichon S. 2005. Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. Biol Psychiatry 58:307-314.
81. Sen S, Burmeister M, Ghosh D. 2004. Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. Am J Med Genet Part B 127B:85-89.
82. Skre I, Onstad S, Edvardsen J, Torgersen S, Kringlen E. 1994. A family study of anxiety disorders: Familial transmission and relationship to mood disorder and psychoactive substance use disorder. Acta Psychiatr Scand 90:366-374.
83. Slade T, Watson D. 2006. The structure of common DSM-IV and ICD-10 mental disorders in the Australian general population. Psychol Med 36:1593-1600.
84. Stein MB, Fallin MD, Schork NJ, Gelernter J. 2005. COMT polymorphisms and anxiety-related personality traits. Neuropsychopharmacology 30:2092-2102.
85. Strauss J, Barr CL, George CJ, King N, Shaikh S, Devlin B, Kovacs M, Kennedy JL. 2004. Association study of brain-derived neurotrophic factor in adults with a history of childhood onset mood disorder. Am J Med Genet Part B Neuropsychiatr Genet 131B:16-19.
86. Strauss J, Barr CL, George CJ, Devlin B, Vetro A, Kiss E, Baji I, King N, Shaikh S, Lanktree M, Kovacs M, Kennedy JL. 2005. Brain-derived neurotrophic factor variants are associated with childhood-onset mood disorder: Confirmation in a Hungarian sample. Mol Psychiatry 10:861-867.
87. Sullivan PF, Neale MC, Kendler KS. 2000. Genetic epidemiology of major depression: Review and meta-analysis. Am J Psychiatry 157:1552-1562.
88. Thorgeirsson TE, Oskarsson H, Desnica N, Kostic JP, Stefansson JG, Kolbeinsson H, Lindal E, Gagunashvili N, Frigge ML, Kong A, Stefansson K, Gulcher JR. 2003. Anxiety with panic disorder linked to chromosome 9q in Iceland. Am J Hum Genet 72:1221-1230.
89. Vollebergh WA, Iedema J, Bijl RV, de Graaf R, Smit F, Ormel J. 2001. The structure and stability of common mental disorders: The NEMESIS study. Arch Gen Psychiatry 58:597-603.
90. Walitza S, Wewetzer C, Warnke A, Gerlach M, Geller F, Gerber G, Gorg T, Herpertz-Dahlmann B, Schulz E, Remschmidt H, Hebebrand J, Hinney A. 2002. 5-HT2A promoter polymorphism -1438G/A in children and adolescents with obsessive-compulsive disorders. Mol Psychiatry 7:1054-1057.
91. Weissman MM. 1990. Evidence for comorbidity of anxiety and depression: Family and genetic studies of children. In: Maser JD, Cloninger CR, editors. Comorbidity of mood and anxiety disorders. Washington, DC: American Psychiatric Press, Inc.
92. Weissman MM, Wickramaratne P, Nomura Y, Warner V, Verdeli H, Pilowsky DJ, Grillon C, Bruder G. 2005. Families at high and low risk for depression a 3-generation study. Arch Gen Psychiatry 62:29-36.