Genetic variation in 5HTTLPR is associated with emotional resilience

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 150, Issue 7, 2009, Pages 900-906

  Stein, Murray B ^a,b   Campbell Sills, Laura ^a   Gelernter, Joel ^c,d  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d VA CONNECTICUT HEALTHCARE SYSTEM   (United States)

Author keywords

5HTTLPR; Depression; Emotional resilience; Gene; Serotonin; Stress

Indexed keywords

GENOMIC DNA; SEROTONIN TRANSPORTER;

ADULT; ALLELE; ARTICLE; BLOOD SALVAGE; EMOTIONAL STABILITY; FEMALE; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HUMAN; LIFE STRESS; MAJOR CLINICAL STUDY; MALE; MENTAL HEALTH; PHENOTYPE; PRIORITY JOURNAL; PSYCHOMETRY; SCORING SYSTEM; STRESS;

ADOLESCENT; ADULT; DEPRESSION; EMOTIONS; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HUMANS; MALE; MULTIVARIATE ANALYSIS; NEUROTIC DISORDERS; QUESTIONNAIRES; REGRESSION ANALYSIS; RESILIENCE, PSYCHOLOGICAL; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; YOUNG ADULT;

EID: 70349311864     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.30916     Document Type: Article

References (67)

1. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. 1961. An inventory for measuring depression. Arch Gen Psychiatry 4:561-571.
2. Bernstein DP, Fink L, Handelsman L, Lovejoy M, Wenzel K, Sapareto E, Ruggiero J. 1994. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry 151:1132-1136. (Pubitemid 24240954)
3. Bertolino A, Arciero G, Rubino V, Latorre V, De Candia M, Mazzola V, Blasi G, Caforio G, Hariri A, Kolachana B, Nardini M, Weinberger DR, Scarabino T. 2005. Variation of human amygdala response during threatening stimuli as a function of 5′HTTLPR genotype and personality style. Biol Psychiatry 57:1517-1525. (Pubitemid 40805381)
4. Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, Ressler KJ. 2008. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. J Am Med Assoc 299:1291-1305.
5. Bonanno GA. 2004. Loss, trauma, and human resilience - Have we underestimated the human capacity to thrive after extremely aversive events? Am Psychol 59:20-28.
6. Campbell-Sills L, Stein MB. 2007. Psychometric analysis and refinement of the Connor-Davidson resilience scale (CD-RISC): Validation of a 10-item measure of resilience. J Trauma Stress 20:1019-1028.
7. Campbell-Sills L, Cohan SL, Stein MB. 2006. Relationship of resilience to personality, coping, and psychiatric symptoms in young adults. Behav Res Ther 44:585-599. (Pubitemid 43220456)
8. Canli T, Lesch KP. 2007. Long story short: The serotonin transporter in emotion regulation and social cognition. Nat Neurosci 10:1103-1109. (Pubitemid 47339957)
9. Caspi A, Moffitt TE. 2006. Gene-environment interactions in psychiatry: Joining forces with neuroscience. Nat Rev Neurosci 7:583-590. (Pubitemid 43995433)
10. 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. (Pubitemid 36877077)
11. Charney DS. 2004. Psychobiological mechanisms of resilience and vulnerability: Implications for successful adaptation to extreme stress. Am J Psychiatry 161:195-216.
12. Chorbov VM, Lobos EA, Todorov AA, Heath AC, Botteron KN, Todd RD. 2007. Relationship of 5-HTTLPR genotypes and depression risk in the presence of trauma in a female twin sample. Am J Med Genet Part B 144B:830-833.
13. Connor KM, Davidson JR. 2003. Development of a new resilience scale: The Connor-Davidson Resilience Scale (CD-RISC). Depress Anxiety 18:76-82. (Pubitemid 37175584)
14. Costa PT Jr, McCrae RR. 1992. NEO PI-R professional manual. Odessa, FL:Psychological Assessment Resources, Inc.
15. Davidson J, Watkins L, Owens M, Krulewicz S, Connor K, Carpenter D, Krishnan R, Nemeroff C. 2005. Effects of paroxetine and venlafaxine XR on heart rate variability in depression. J Clin Psychopharmacol 25:480-484. (Pubitemid 41368373)
16. Dziedzicka-Wasylewska M, Faron-Gorecka A, Kusmider M, Drozdowska E, Rogoz Z, Siwanowicz J, Caron MG, Bonisch H. 2006. Effect of antidepressant drugs in mice lacking the norepinephrine transporter. Neuropsychopharmacology 31:2424-2432. (Pubitemid 44607060)
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. (Pubitemid 39381955)
18. Falush D, Stephens M, Pritchard JK. 2003. Inference of population structure using multilocus genotype data: Linked loci and correlated allele frequencies. Genetics 164:1567-1587. (Pubitemid 37102217)
19. Galea S, Vlahov D, Resnick H, Ahern J, Susser E, Gold J, Bucuvalas M, Kilpatrick D. 2003. Trends of probable post-traumatic stress disorder in New York City after the September 11 terrorist attacks. Am J Epidemiol 158:514-524. (Pubitemid 37093227)
20. Galea S, Brewin CR, Gruber M, Jones RT, King DW, King LA, McNally RJ, Ursano RJ, Petukhova M, Kessler RC. 2007. Exposure to hurricane-related stressors and mental illness after Hurricane Katrina. Arch Gen Psychiatry 64:1427-1434. (Pubitemid 350223561)
21. Gelernter J, Kranzler H, Cubells JF. 1997. Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects. Hum Genet 101:243-246. (Pubitemid 28014742)
22. Gillespie NA, Whitfield JB, Williams B, Heath AC, Martin NG. 2005. The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression. Psychol Med 35:101-111. (Pubitemid 40201920)
23. Grabe HJ, Lange M, Wolff B, Volzke H, Lucht M, Freyberger HJ, John U, Cascorbi I. 2005. Mental and physical distress is modulated by a polymorphism in the 5-HT transporter gene interacting with social stressors and chronic disease burden. Mol Psychiatry 10:220-224. (Pubitemid 40188517)
24. Gross JJ, John OP. 2003. Individual differences in two emotion regulation processes: Implications for affect, relationships, and well-being. J Pers Soc Psychol 85:348-362.
25. Gunthert KC, Conner TS, Armeli S, Tennen H, Covault J, Kranzler HR. 2007. Serotonin transporter gene polymorphism (5-HTTLPR) and anxiety reactivity in daily life: A daily process approach to gene-environment interaction. Psychosom Med 69:762-768. (Pubitemid 350287484)
26. Hare TA, Tottenham N, Davidson MC, Glover GH, Casey BJ. 2005. Contributions of amygdala and striatal activity in emotion regulation. Biol Psychiatry 57:624-632. (Pubitemid 40416706)
27. Hariri AR, Holmes A. 2006. Genetics of emotional regulation: The role of the serotonin transporter in neural function. Trends Cogn Sci 10:182-191.
28. Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, Weinberger DR. 2005. A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 62:146-152. (Pubitemid 40189130)
29. Heinz A, Smolka MN, Braus DF, Wrase J, Beck A, Flor H, Mann K, Schumann G, Buchel C, Hariri AR, Weinberger DR. 2007. Serotonin transporter genotype (5-HTTLPR): Effects of neutral and undefined conditions on amygdala activation. Biol Psychiatry 61:1011-1014. (Pubitemid 46482463)
30. Hettema JM, An SS, Bukszar J, van den Oord EJ, Neale MC, Kendler KS, Chen X. 2008a. Catechol-O-methyltransferase contributes to genetic susceptibility shared among anxiety spectrum phenotypes. Biol Psychiatry 64:302-310.
31. Hettema JM, An SS, van den Oord EJ, Neale MC, Kendler KS, Chen X. 2008b. Association study between the serotonin 1A receptor (HTR1A) gene and neuroticism, major depression, and anxiety disorders. Am J Med Genet Part B 147B:661-666.
32. Holmes A. 2008. Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neurosci Biobehav Rev 32:1293-1314.
33. Hu X, Oroszi G, Chun J, Smith TL, Goldman D, Schuckit MA. 2005. An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. Alcohol Clin Exp Res 29:8-16. (Pubitemid 40129206)
34. Jacobs N, Kenis G, Peeters F, Derom C, Vlietinck R, van Os J. 2006. Stress-related negative affectivity and genetically altered serotonin transporter function: Evidence of synergism in shaping risk of depression. Arch Gen Psychiatry 63:989-996. (Pubitemid 44330457)
35. Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH, Gelernter J. 2004. Social supports and serotonin transporter gene moderate depression in maltreated children. Proc Natl Acad Sci USA 101:17316-17321. (Pubitemid 39627817)
36. Kaufman J, Yang BZ, Douglas-Palumberi H, Grasso D, Lipschitz D, Houshyar S, Krystal JH, Gelernter J. 2006. Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biol Psychiatry 59:673-680.
37. Kaufman J, Yang BZ, Douglas-Palumberi H, Crouse-Artus M, Lipschitz D, Krystal JH, Gelernter J. 2007. Genetic and environmental predictors of early alcohol use. Biol Psychiatry 61:1228-1234. (Pubitemid 46726258)
38. Kendler KS. 2005. "A gene for. . .": The nature of gene action in psychiatric disorders. Am J Psychiatry 162:1243-1252.
39. 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. (Pubitemid 40628882)
40. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. 1995. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 52:1048-1060.
41. King DW, King LA, Foy DW, Keane TM, Fairbank JA. 1999. Posttraumatic stress disorder in a national sample of female and male Vietnam veterans: Risk factors, war-zone stressors, and resilience-recovery variables. J Abnorm Psychol 108:164-170.
42. Lesch K-P, Bengel D, Heils A, Sabol SA, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL. 1996. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527-1531. (Pubitemid 26403928)
43. Luthar SS, Cicchetti D, Becker B. 2000. The construct of resilience: A critical evaluation and guidelines for future work. Child Dev 71:543-562.
44. Middeldorp CM, Cath DC, Van Dyck R, Boomsma DI. 2005. The comorbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies. Psychol Med 35:611-624.
45. Otte C, McCaffery J, Ali S, Whooley MA. 2007. Association of a serotonin transporter polymorphism (5-HTTLPR) with depression, perceived stress, and norepinephrine in patients with coronary disease: The Heart and Soul Study. Am J Psychiatry 164:1379-1384. (Pubitemid 47461138)
46. Parsey RV, Hastings RS, Oquendo MA, Hu X, Goldman D, Huang YY, Simpson N, Arcement J, Huang Y, Ogden RT, Van Heertum RL, Arango V, Mann JJ. 2006. Effect of a triallelic functional polymorphism of the serotonin-transporter-linked promoter region on expression of serotonin transporter in the human brain. Am J Psychiatry 163:48-51. (Pubitemid 43050102)
47. Phan KL, Taylor SF, Welsh RC, Decker LR, Noll DC, Nichols TE, Britton JC, Liberzon I. 2003. Activation of the medial prefrontal cortex and extended amygdala by individual ratings of emotional arousal: A fMRI study. Biol Psychiatry 53:211-215. (Pubitemid 36135931)
48. Phan KL, Fitzgerald DA, Nathan PJ, Moore GJ, Uhde TW, Tancer ME. 2005. Neural substrates for voluntary suppression of negative affect: A functional magnetic resonance imaging study. Biol Psychiatry 57:210-219. (Pubitemid 40187364)
49. Pritchard JK, Rosenberg NA. 1999. Use of unlinked genetic markers to detect population stratification in association studies. Am J Hum Genet 65:220-228.
50. Pritchard JK, Stephens M, Rosenberg NA, Donnely P. 2000. Association mapping in structured populations. Am J Hum Genet 67:170-181.
51. Scher CD, Stein MB, Asmundson GJ, McCreary DR, Forde DR. 2001. The childhood trauma questionnaire in a community sample: Psychometric properties and normative data. J Traum Stress 14:843-857.
52. 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. (Pubitemid 38299534)
53. Schulze TG, Muller DJ, Krauss H, Scherk H, Ohlraun S, Syagailo YV, Windemuth C, Neidt H, Grassle M, Papassotiropoulos A, Heun R, Nothen MM, Maier W, Lesch KP, Rietschel M. 2000. Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder. Am J Med Genet 96:801-803.
54. 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. (Pubitemid 38542320)
55. Smolka MN, Schumann G, Wrase J, Grusser SM, Flor H, Mann K, Braus DF, Goldman D, Buchel C, Heinz A. 2005. Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. J Neurosci 25:836-842. (Pubitemid 40170998)
56. StataCorp. 2007. Stata Statistical Software [Release 10.0]. College Station, TX:Stata Corporation.
57. Stein MB, Seedat S, Gelernter J. 2006. Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder. Psychopharmacology 187:68-72. (Pubitemid 43876918)
58. Stein MB, Schork NJ, Gelernter J. 2008. Gene-by-environment (serotonin transporter and childhood maltreatment) interaction for anxiety sensitivity, an intermediate phenotype for anxiety disorders. Neuropsychopharmacology 33:312-319. (Pubitemid 350243362)
59. Surtees PG, Wainwright NW, Willis-Owen SA, Luben R, Day NE, Flint J. 2006. Social adversity, the serotonin transporter (5-HTTLPR) polymorphism and major depressive disorder. Biol Psychiatry 59:224-229. (Pubitemid 43208968)
60. Tsuang M. 2000. Genes, environment, and mental health wellness. Am J Psychiatry 157:489-491. (Pubitemid 30191185)
61. Tugade MM, Fredrickson BL. 2004. Resilient individuals use positive emotions to bounce back from negative emotional experiences. J Pers Soc Psychol 86:320-333.
62. Wellman CL, Izquierdo A, Garrett JE, Martin KP, Carroll J, Millstein R, Lesch KP, Murphy DL, Holmes A. 2007. Impaired stress-coping and fear extinction and abnormal corticolimbic morphology in serotonin transporter knock-out mice. J Neurosci 27:684-691. (Pubitemid 46143772)
63. Wendland JR, Martin BJ, Kruse MR, Lesch KP, Murphy DL. 2006. Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry 11:224-226.
64. Wilhelm K, Mitchell PB, Niven H, Finch A, Wedgwood L, Scimone A, Blair IP, Parker G, Schofield PR. 2006. Life events, first depression onset and the serotonin transporter gene. Br J Psychiatry 188:210-215. (Pubitemid 43341646)
65. Yang BZ, Zhao H, Kranzler HR, Gelernter J. 2005. Practical population group assignment with selected informative markers: Characteristics and properties of Bayesian clustering via STRUCTURE. Genet Epidemiol 28:302-312. (Pubitemid 40559543)
66. Zalsman G, Huang YY, Oquendo MA, Burke AK, Hu XZ, Brent DA, Ellis SP, Goldman D, Mann JJ. 2006. Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression. Am J Psychiatry 163:1588-1593. (Pubitemid 44465760)
67. Zhou Z, Zhu G, Hariri AR, Enoch MA, Scott D, Sinha R, Virkkunen M, Mash DC, Lipsky RH, Hu XZ, Hodgkinson CA, Xu K, Buzas B, Yuan Q, Shen PH, Ferrell RE, Manuck SB, Brown SM, Hauger RL, Stohler CS, Zubieta JK, Goldman D. 2008. Genetic variation in human NPY expression affects stress response and emotion. Nature 452:997-1001. (Pubitemid 351589618)