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Behavior Genetics

, Volume 40, Issue 4, pp 518–532 | Cite as

Association of Existing and New Candidate Genes for Anxiety, Depression and Personality Traits in Older People

  • Michelle Luciano
  • Lorna M. Houlihan
  • Sarah E. Harris
  • Alan J. Gow
  • Caroline Hayward
  • John M. Starr
  • Ian J. Deary
Original Research

Abstract

Genetic variants that have previously been associated with personality traits and/or psychological distress, or inflammatory marker levels were investigated for their relationship to self-rated personality traits, anxiety, and depression in two elderly Scottish cohorts. Ten genes (29 SNPs) were investigated in the Lothian Birth Cohort 1936 (~70 years, N = 1,091). Four of these genes and seven others (35 SNPs) were tested in the Lothian Birth Cohort 1921 who were measured on the same traits and states on two occasions (~80 years, N = 550; 87 years, N = 229). For previously investigated candidate genes, some support (at a nominal significance level of 0.05/0.01) was found for association between NOS1 and personality traits (especially extraversion), PSEN1 and depression/neuroticism, and GRIK3 and depression. Of the inflammatory marker candidate genes, TF showed some association with psychological distress. No SNPs withstood the correction to significance level for multiple testing. Nevertheless, the results will be of importance to future meta-analyses of these candidate genes in relation to psychological distress and personality.

Keywords

Anxiety Depression Personality Inflammatory marker genes Candidate genes Genetic association 

Notes

Acknowledgments

We thank the LBC1921 and LBC1936 participants. We thank the LBC1936 study Secretary Paula Davies. We thank Michelle Taylor, Janie Corley, Caroline Brett, Alison Pattie, Martha Whiteman and Caroline Cameron for data collection and data entry. We thank the staff at Lothian Health Board, and the staff at the SCRE Centre, University of Glasgow; and Jenny Huffman for performing some of the genotyping. The LBC1921 data described here were collected in waves funded by the BBSRC and the Chief Scientist Office of the Scottish Executive. The LBC1936 was supported by a programme grant (to IJD and JMS) from Research into Ageing, which continues with funding from Help the Aged as The Disconnected Mind. The work was undertaken by The University of Edinburgh Centre for Cognitive Aging and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative. Funding (to IJD and JMS) from the BBSRC, EPSRC, ESRC and MRC is gratefully acknowledged. ML is a Royal Society of Edinburgh/Lloyds TSB Foundation for Scotland Personal Research Fellow.

References

  1. Almeida OP, Norman PE, Allcock R, Bockxmeer FV, Hankey GJ, Jamrozik K, Flicker L (2009) Polymorphisms of the CRP gene inhibit inflammatory response and increase susceptibility to depression: the health in men study. Int J Epidemiol 38(4):1049–1059CrossRefPubMedGoogle Scholar
  2. Baekken PM, Skorpen F, Stordal E, Zwart JA, Hagen K (2008) Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: the Nord-Trondelag Health Study (HUNT). BMC Psychiatry 8:48CrossRefPubMedGoogle Scholar
  3. Begni S, Popoli M, Moraschi S, Bignotti S, Tura GB, Gennarelli M (2002) Association between the ionotropic glutamate receptor kainate 3 (GRIK3) ser310ala polymorphism and schizophrenia. Mol Psychiatry 7(4):416–418CrossRefPubMedGoogle Scholar
  4. Bernstein HG, Heinemann A, Krell D, Mawrin C, Bielau H, Danos P, Diekmann S, Keilhoff G, Bogerts B, Baumann B (2002) Further immunohistochemical evidence for impaired NO signaling in the hypothalamus of depressed patients. Ann N Y Acad Sci 973:91–93CrossRefPubMedGoogle Scholar
  5. Carey G, DiLalla DL (1994) Personality and psychopathology: genetic perspectives. J Abnorm Psychol 103(1):32–43CrossRefPubMedGoogle Scholar
  6. Chrapko WE, Jurasz P, Radomski MW, Lara N, Archer SL, Le Melledo JM (2004) Decreased platelet nitric oxide synthase activity and plasma nitric oxide metabolites in major depressive disorder. Biol Psychiatry 56(2):129–134CrossRefPubMedGoogle Scholar
  7. Christiansen L, Tan Q, Iachina M, Bathum L, Kruse TA, McGue M, Christensen K (2007) Candidate gene polymorphisms in the serotonergic pathway: influence on depression symptomatology in an elderly population. Biol Psychiatry 61(2):223–230CrossRefPubMedGoogle Scholar
  8. Cohen-Woods S, Gaysina D, Craddock N, Farmer A, Gray J, Gunasinghe C, Hoda F, Jones L, Knight J, Korszun A, Owen MJ, Sterne A, Craig IW, McGuffin P (2009) Depression Case Control (DeCC) Study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder. Hum Mol Genet 18(8):1504–1509CrossRefPubMedGoogle Scholar
  9. Costa PT Jr, McCrae RR (1992) NEO PI-R professional manual. Psychological Assessment Resources, Odessa, FLGoogle Scholar
  10. 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(5):446–458CrossRefPubMedGoogle Scholar
  11. Deary IJ, Whiteman MC, Starr JM, Whalley LJ, Fox HC (2004) The impact of childhood intelligence on later life: following up the Scottish mental surveys of 1932 and 1947. J Pers Soc Psychol 86(1):130–147CrossRefPubMedGoogle Scholar
  12. Deary IJ, Gow AJ, Taylor MD, Corley J, Brett C, Wilson V, Campbell H, Whalley LJ, Visscher PM, Porteous DJ, Starr JM (2007) The Lothian Birth Cohort 1936: a study to examine influences on cognitive ageing from age 11 to age 70 and beyond. BMC Geriatr 7:28CrossRefPubMedGoogle Scholar
  13. Elgun S, Kumbasar H (2000) Increased serum arginase activity in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 24(2):227–232CrossRefPubMedGoogle Scholar
  14. Fatemi SH, Earle JA, Stary JM, Lee S, Sedgewick J (2001) Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia. Neuroreport 12(15):3257–3262CrossRefPubMedGoogle Scholar
  15. Frustaci A, Pozzi G, Gianfagna F, Manzoli L, Boccia S (2008) Meta-analysis of the brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism in anxiety disorders and anxiety-related personality traits. Neuropsychobiology 58(3–4):163–170CrossRefPubMedGoogle Scholar
  16. Goldberg L (1999) A broad-bandwidth, public-domain, personality inventory measuring the lower-level facets of several five-factor models. In: Mervielde I, Deary IJ, de Fruyt F, Ostendorf F (eds) Personality psychology in Europe. Tilburg University Press, Tilburg, The NetherlandsGoogle Scholar
  17. Gow AJ, Whiteman MC, Pattie A, Deary IJ (2005a) Goldberg’s ‘IPIP’ big-five factor markers: internal consistency and concurrent validation in Scotland. Personality Individ Differ 39(2):317–329CrossRefGoogle Scholar
  18. Gow AJ, Whiteman MC, Pattie A, Deary IJ (2005b) The personality–intelligence interface: insights from an ageing cohort. Personality Individ Differ 39(4):751–761CrossRefGoogle Scholar
  19. Groves JO (2007) Is it time to reassess the BDNF hypothesis of depression? Mol Psychiatry 12(12):1079–1088CrossRefPubMedGoogle Scholar
  20. Harris SE, Wright AF, Hayward C, Starr JM, Whalley LJ, Deary IJ (2005) The functional COMT polymorphism, Val 158 Met, is associated with logical memory and the personality trait intellect/imagination in a cohort of healthy 79 year olds. Neurosci Lett 385(1):1–6CrossRefPubMedGoogle Scholar
  21. Harris SE, Fox H, Wright AF, Hayward C, Starr JM, Whalley LJ, Deary IJ (2006) The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills. Mol Psychiatry 11(5):505–513CrossRefPubMedGoogle Scholar
  22. Harris SE, Fox H, Wright AF, Hayward C, Starr JM, Whalley LJ, Deary IJ (2007) A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition. BMC Genet 8:43CrossRefPubMedGoogle Scholar
  23. Harris SE, Hennah W, Thomson PA, Luciano M, Starr JM, Porteous DJ, Deary IJ (2009) Variation in DISC1 is associated with anxiety, depression and emotional stability in elderly women. Mol Psychiatry (in press)Google Scholar
  24. Heinrichs M, Domes G (2008) Neuropeptides and social behaviour: effects of oxytocin and vasopressin in humans. Prog Brain Res 170:337–350CrossRefPubMedGoogle Scholar
  25. Houlihan LM, Harris SE, Luciano M, Gow AJ, Starr JM, Visscher PM, Deary IJ (2009) Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936. Genes Brain Behav 8(2):238–247CrossRefPubMedGoogle Scholar
  26. Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71(2):171–186CrossRefPubMedGoogle Scholar
  27. Ishii G, Suzuki A, Oshino S, Shiraishi H, Matsumoto Y, Otani K, Goto K (2007) Association study of catechol-O-methyltransferase Val158Met polymorphism with personality traits in Japanese healthy volunteers. Eur Psychiatry 22(7):462–465CrossRefPubMedGoogle Scholar
  28. Jansson M, Gatz M, Berg S, Johansson B, Malmberg B, McClearn GE, Schalling M, Pedersen NL (2003) Association between depressed mood in the elderly and a 5-HTR2A gene variant. Am J Med Genet B Neuropsychiatr Genet 120B(1):79–84CrossRefPubMedGoogle Scholar
  29. Jylhä P, Isometsä E (2006) The relationship of neuroticism and extraversion to symptoms of anxiety and depression in the general population. Depress Anxiety 23(5):281–289CrossRefPubMedGoogle Scholar
  30. Kim JW, Biederman J, Arbeitman L, Fagerness J, Doyle AE, Petty C, Perlis RH, Purcell S, Smoller JW, Faraone SV, Sklar P (2007) Investigation of variation in SNAP-25 and ADHD and relationship to co-morbid major depressive disorder. Am J Med Genet B Neuropsychiatr Genet 144B(6):781–790CrossRefPubMedGoogle Scholar
  31. Krueger RF, Johnson W (2008) Behavioral genetics and personality. In: Pervin LA, John OP, Robins RW (eds) Handbook of personality: theory and research. Guilford Press, GuilfordGoogle Scholar
  32. Loehlin J, Neiderhiser J, Reiss D (2003) The behavior genetics of personality and the NEAD study. J Res Pers 37:373–387CrossRefGoogle Scholar
  33. Lopez-Leon S, Janssens AC, Gonzalez-Zuloeta Ladd AM, Del-Favero J, Claes SJ, Oostra BA, van Duijn CM (2008) Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry 13(8):772–785CrossRefPubMedGoogle Scholar
  34. Luo X, Kranzler HR, Zuo L, Zhang H, Wang S, Gelernter J (2007) CHRM2 variation predisposes to personality traits of agreeableness and conscientiousness. Hum Mol Genet 16(13):1557–1568CrossRefPubMedGoogle Scholar
  35. Margis R, Zanatto VC, Tramontina F, Vinade E, Lhullier F, Portela LV, Souza DO, Dalmaz C, Kapczinski F, Goncalves CA (2004) Changes in S100B cerebrospinal fluid levels of rats subjected to predator stress. Brain Res 1028(2):213–218CrossRefPubMedGoogle Scholar
  36. 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(6):598–605CrossRefPubMedGoogle Scholar
  37. 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(5):611–624CrossRefPubMedGoogle Scholar
  38. Minelli A, Scassellati C, Bonvicini C, Perez J, Gennarelli M (2009) An association of GRIK3 Ser310Ala functional polymorphism with personality traits. Neuropsychobiology 59(1):28–33CrossRefPubMedGoogle Scholar
  39. Nelson RJ, Demas GE, Huang PL, Fishman MC, Dawson VL, Dawson TM, Snyder SH (1995) Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. Nature 378(6555):383–386CrossRefPubMedGoogle Scholar
  40. Nes RB, Roysamb E, Reichborn-Kjennerud T, Harris JR, Tambs K (2007) Symptoms of anxiety and depression in young adults: genetic and environmental influences on stability and change. Twin Res Hum Genet 10(3):450–461CrossRefPubMedGoogle Scholar
  41. Nyholt DR (2004) A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74(4):765–769CrossRefPubMedGoogle Scholar
  42. O’Brien SM, Scott LV, Dinan TG (2004) Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol 19(6):397–403CrossRefPubMedGoogle Scholar
  43. Ohara K, Nagai M, Suzuki Y, Yoshida K, Tsukamoto T, Ohara K (1999) Apolipoprotein E epsilon 4 allele and Japanese late-onset depressive disorders. Biol Psychiatry 45(3):308–312CrossRefPubMedGoogle Scholar
  44. Ohara K, Suzuki Y, Ohta D, Ohara K (2000) Presenilin-1 in late-onset depressive disorder. Psychiatry Res 95(1):83–86CrossRefPubMedGoogle Scholar
  45. Pitsavos C, Panagiotakos DB, Papageorgiou C, Tsetsekou E, Soldatos C, Stefanadis C (2006) Anxiety in relation to inflammation and coagulation markers, among healthy adults: the ATTICA study. Atherosclerosis 185(2):320–326CrossRefPubMedGoogle Scholar
  46. Preville M, Boyer R, Grenier S, Dube M, Voyer P, Punti R, Baril MC, Streiner DL, Cairney J, Brassard J (2008) The epidemiology of psychiatric disorders in Quebec’s older adult population. Can J Psychiatry 53(12):822–832PubMedGoogle Scholar
  47. Purba JS, Hoogendijk WJ, Hofman MA, Swaab DF (1996) Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 53(2):137–143PubMedGoogle Scholar
  48. Purcell S, Cherny SS, Sham PC (2003) Genetic power calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19(1):149–150CrossRefPubMedGoogle Scholar
  49. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575CrossRefPubMedGoogle Scholar
  50. Schiffer HH, Heinemann SF (2007) Association of the human kainate receptor GluR7 gene (GRIK3) with recurrent major depressive disorder. Am J Med Genet B Neuropsychiatr Genet 144B(1):20–26CrossRefPubMedGoogle Scholar
  51. Smith RS (1991) The macrophage theory of depression. Med Hypotheses 35(4):298–306CrossRefPubMedGoogle Scholar
  52. Sorbi S, Nacmias B, Tedde A, Forleo P, Piacentini S, Latorraca S, Amaducci L (1997) Presenilin-1 gene intronic polymorphism in sporadic and familial Alzheimer’s disease. Neurosci Lett 222(2):132–134CrossRefPubMedGoogle Scholar
  53. Suchankova P, Henningsson S, Baghaei F, Rosmond R, Holm G, Ekman A (2009) Genetic variability within the innate immune system influences personality traits in women. Genes Brain Behav 8(2):212–217CrossRefPubMedGoogle Scholar
  54. van Amsterdam JG, Opperhuizen A (1999) Nitric oxide and biopterin in depression and stress. Psychiatry Res 85(1):33–38CrossRefPubMedGoogle Scholar
  55. Verhagen M, van der Meij A, van Deurzen PA, Janzing JG, Arias-Vasquez A, Buitelaar JK, Franke B (2008) Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Mol Psychiatry. doi: 10.1038/mp.2008.109
  56. Wang JC, Hinrichs AL, Stock H, Budde J, Allen R, Bertelsen S, Kwon JM, Wu W, Dick DM, Rice J, Jones K, Nurnberger J I Jr, Tischfield J, Porjesz B, Edenberg HJ, Hesselbrock V, Crowe R, Schuckit M, Begleiter H, Reich T, Goate AM, Bierut LJ (2004) Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet 13(17):1903–1911CrossRefPubMedGoogle Scholar
  57. Wragg M, Hutton M, Talbot C (1996) Genetic association between intronic polymorphism in presenilin-1 gene and late-onset Alzheimer’s disease. Alzheimer’s Disease Collaborative Group. Lancet 347(9000):509–512CrossRefPubMedGoogle Scholar
  58. Wray NR, Birley AJ, Sullivan PF, Visscher PM, Martin NG (2007) Genetic and phenotypic stability of measures of neuroticism over 22 years. Twin Res Hum Genet 10(5):695–702CrossRefPubMedGoogle Scholar
  59. Wray NR, James MR, Dumenil T, Handoko HY, Lind PA, Montgomery GW, Martin NG (2008) Association study of candidate variants of COMT with neuroticism, anxiety and depression. Am J Med Genet B Neuropsychiatr Genet 147B(7):1314–1318CrossRefPubMedGoogle Scholar
  60. Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6):361–370CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michelle Luciano
    • 1
    • 2
  • Lorna M. Houlihan
    • 1
    • 2
  • Sarah E. Harris
    • 1
    • 3
  • Alan J. Gow
    • 1
    • 2
  • Caroline Hayward
    • 4
  • John M. Starr
    • 1
    • 5
  • Ian J. Deary
    • 1
    • 2
  1. 1.Centre for Cognitive Ageing and Cognitive EpidemiologyUniversity of EdinburghEdinburghScotland, UK
  2. 2.Department of PsychologyUniversity of EdinburghEdinburghScotland, UK
  3. 3.Medical Genetics SectionUniversity of EdinburghEdinburghUK
  4. 4.Institute of Genetics and Molecular Medicine, MRC Human Genetics UnitWestern General HospitalEdinburghUK
  5. 5.Department of Geriatric MedicineUniversity of Edinburgh, Royal Victoria HospitalEdinburghUK

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