Effects of genetic and early environmental risk factors for depression on serotonin transporter expression and methylation profiles

Translational Psychiatry

Volumn 4, Issue , 2014, Pages

  Wankerl, M ^a   Miller, R ^a   Kirschbaum, C ^a   Hennig, J ^b   Stalder, T ^a   Alexander, N ^a  

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b JUSTUS LIEBIG UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; SEROTONIN TRANSPORTER; SLC6A4 PROTEIN, HUMAN;

ADULT; ALLELE; ARTICLE; CPG ISLAND; DEPRESSION; DISEASE PREDISPOSITION; DNA METHYLATION; EPIGENETICS; FEMALE; GENE EXPRESSION PROFILING; GENOTYPE ENVIRONMENT INTERACTION; HEREDITY; HUMAN; LIFE STRESS; LIFESPAN; MAJOR CLINICAL STUDY; MALE; PILOT STUDY; PRENATAL STRESS; PYROSEQUENCING; RISK FACTOR; SELF REPORT; SEROTONINERGIC SYSTEM; CHILD; CHILD ABUSE; COMPLICATION; DNA SEQUENCE; GENETIC PREDISPOSITION; GENETICS; MENTAL STRESS; METABOLISM; PATHOPHYSIOLOGY; PREGNANCY; PREGNANCY COMPLICATION; PRENATAL EXPOSURE; PROCEDURES; PSYCHOLOGY; YOUNG ADULT; CHILDHOOD TRAUMA QUESTIONNAIRE; CONTROLLED STUDY; DNA MODIFICATION; IN VIVO STUDY; POLYMORPHIC LOCUS; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN METHYLATION;

ADULT; CHILD; CHILD ABUSE; CPG ISLANDS; DEPRESSION; DNA METHYLATION; FEMALE; GENE-ENVIRONMENT INTERACTION; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; PREGNANCY; PREGNANCY COMPLICATIONS; PRENATAL EXPOSURE DELAYED EFFECTS; RISK FACTORS; RNA, MESSENGER; SEQUENCE ANALYSIS, DNA; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; STRESS, PSYCHOLOGICAL; YOUNG ADULT;

EID: 84902774378     PISSN: None     EISSN: 21583188     Source Type: Journal    
DOI: 10.1038/tp.2014.37     Document Type: Article

References (80)

1. Klengel T, Binder EB. Gene-environment interactions in major depressive disorder. Can J Psychiatry 2013; 58: 76-83.
2. Lesch K-PP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527-1531. (Pubitemid 26403928)
3. Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003; 301: 386-389. (Pubitemid 36877077)
4. Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 2010; 167: 509-527.
5. Wankerl M, Wüst S, Otte C. Current developments and controversies: does the serotonin transporter gene-linked polymorphic region (5-HTTLPR) modulate the association between stress and depression? Curr Opin Psychiatry 2010; 23: 582-587.
6. Uher R, McGuffin P. The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Mol Psychiatry 2010; 15: 18-22.
7. Risch N, Herrell R, Lehner T, Liang K-Y, Eaves L, Hoh J et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 2009; 301: 2462-2471.
8. Karg K, Burmeister M, Shedden K, Sen S. The Serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry 2011; 68: 444-454.
9. Northoff G. Gene, brains, and environment-genetic neuroimaging of depression. Curr Opin Neurobiol 2013; 23: 133-142.
10. Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002; 297: 400-403. (Pubitemid 34790769)
11. Murphy SE, Norbury R, Godlewska BR, Cowen PJ, Mannie ZM, Harmer CJ et al. The effect of the serotonin transporter polymorphism (5-HTTLPR) on amygdala function: a meta-analysis. Mol Psychiatry 2013; 18: 512-520.
12. Gotlib IH, Joormann J, Minor KL, Hallmayer J. HPA axis reactivity: a mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biol Psychiatry 2008; 63: 847-851. (Pubitemid 351458452)
13. Miller R, Wankerl M, Stalder T, Kirschbaum C, Alexander N. The serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cortisol stress reactivity: a meta-analysis. Mol Psychiatry 2013; 9: 1018-1024.
14. Iga J-I, Ueno S-I, Yamauchi K, Motoki I, Tayoshi S, Ohta K et al. Serotonin transporter mRNA expression in peripheral leukocytes of patients with major depression before and after treatment with paroxetine. Neurosci Lett 2005; 389: 12-16. (Pubitemid 41219425)
15. Mehta D, Menke A, Binder EB. Gene expression studies in major depression. Curr Psychiatry Rep 2010; 12: 135-144.
16. Lima L, Mata S, Urbina M. Allelic isoforms and decrease in serotonin transporter mRNA in lymphocytes of patients with major depression. Neuroimmunomodulation 2005; 12: 299-306. (Pubitemid 41318213)
17. Bethea CL, Streicher JM, Mirkes SJ, Sanchez RL, Reddy AP, Cameron JL. Serotoninrelated gene expression in female monkeys with individual sensitivity to stress. Neuroscience 2005; 132: 151-166. (Pubitemid 40380722)
18. Bethea CL, Phu K, Reddy AP, Cameron JL. The effect of short-term stress on serotonin gene expression in high and low resilient macaques. Prog Neuropsychopharmacol Biol Psychiatry 2013; 44: 143-153.
19. Hu X-Z, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD et al. Serotonin transporter promoter gain-of-function genotypes are linked to obsessivecompulsive disorder. Am J Hum Genet 2006; 78: 815-826.
20. Greenberg BD, Tolliver TJ, Huang S-J, Li Q, Bengel D, Murphy DL. Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. Am J Med Genet 1999; 88: 83-87. (Pubitemid 29075327)
21. Stoltenberg SF, Twitchell GR, Hanna GL, Cook EH, Fitzgerald HE, Zucker RA et al. Serotonin transporter promoter polymorphism, peripheral indexes of serotonin function, and personality measures in families with alcoholism. Am J Med Genet 2002; 114: 230-234. (Pubitemid 34160477)
22. Singh YS, Altieri SC, Gilman TL, Michael HM, Tomlinson ID, Rosenthal SJ et al. Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells. Transl Psychiatry 2012; 2: e77.
23. Vijayendran M, Beach SRH, Plume JM, Brody GH, Philibert RA. Effects of genotype and child abuse on DNA methylation and gene expression at the serotonin transporter. Front Psychiatry 2012; 3: 55.
24. van Dyck CH, Malison RT, Staley JK, Jacobsen LK, Seibyl JP, Laruelle M et al. Central serotonin transporter availability measured with [123I]beta-CIT SPECT in relation to serotonin transporter genotype. Am J Psychiatry 2004; 161: 525-531. (Pubitemid 38326108)
25. Praschak-Rieder N, Kennedy J, Wilson AA, Hussey D, Boovariwala A, Willeit M et al. Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen: A [11C] DASB positron emission tomography study. Biol Psychiatry 2007; 62: 327-331. (Pubitemid 47444277)
26. Murthy N, Selvaraj S, Cowen P, Bhagwagar Z. Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [ 11 C] DASB binding in the living brain. NeuroImage 2010; 52: 50-54.
27. Kalbitzer J, Erritzoe D, Holst KK, Nielsen F, Marner L, Lehel S et al. Seasonal changes in brain serotonin transporter binding in short serotonin transporter linked polymorphic region-allele carriers but not in long-allele homozygotes. BPS 2010; 67: 1033-1039.
28. Own LS, Iqbal R, Patel PD. Maternal separation alters serotonergic and HPA axis gene expression independent of separation duration in c57bl/6 mice. Brain Res 2013; 1515: 29-38.
29. Lee J-H, Kim HJ, Kim JG, Ryu V, Kim B-T, Kang D-W et al. Depressive behaviors and decreased expression of serotonin reuptake transporter in rats that experienced neonatal maternal separation. Neurosci Res 2007; 58: 32-39. (Pubitemid 46678488)
30. Gardner KL, Hale MW, Lightman SL, Plotsky PM, Lowry CA. Adverse early life experience and social stress during adulthood interact to increase serotonin transporter mRNA expression. Brain Res 2009; 1305: 47-63.
31. Kinnally EL, Tarara ER, Mason WA, Mendoza SP, Abel K, Lyons LA et al. Serotonin transporter expression is predicted by early life stress and is associated with disinhibited behavior in infant rhesus macaques. Genes Brain Behav 2010; 9: 45-52.
32. Meaney MJ. Epigenetics and the biological definition of gene x environment interactions. Child Dev 2010; 81: 41-79.
33. Philibert RA, Sandhu H, Hollenbeck N, Gunter T, Adams W, Madan A. The relationship of 5HTT( SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am J Med Genet 2008; 147B: 543-549. (Pubitemid 351961655)
34. Olsson CA, Foley DL, Parkinson-Bates M, Byrnes G, McKenzie M, Patton GC et al. Prospects for epigenetic research within cohort studies of psychological disorder: a pilot investigation of a peripheral cell marker of epigenetic risk for depression. Biol Psychol 2010; 83: 159-165.
35. Kinnally EL, Capitanio JP, Leibel R, Deng L, LeDuc C, Haghighi F et al. Epigenetic regulation of serotonin transporter expression and behavior in infant Rhesus macaques. Genes Brain Behav 2010; 9: 575-582.
36. Beach SRH, Brody GH, Todorov AA, Gunter TD, Philibert RA. Methylation at SLC6A4 is linked to family history of child abuse: an examination of the Iowa Adoptee sample. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 710-713.
37. Beach SRH, Brody GH, Todorov AA, Gunter TD, Philibert RA. Methylation at 5HTT mediates the impact of child sex abuse on women's antisocial behavior: an examination of the Iowa adoptee sample. Psychosom Med 2011; 73: 83-87.
38. Ouellet-Morin I, Wong CCY, Danese A, Pariante CM, Papadopoulos AS, Mill J et al. Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins. Psychol Med 2013; 9: 1813-1823.
39. Kang H-J, Kim J-M, Stewart R, Kim S-Y, Bae K-Y, Kim S-W et al. Association of SLC6A4 methylation with early adversity, characteristics and outcomes in depression. Prog Neuropsychopharmacol Biol Psychiatry 2013; 44: 23-28.
40. Philibert R, Madan A, Andersen A. Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island-Philibert-2006- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics-Wiley Online Library. Am J Med Genet Part B 2007; 144B: 101-105.
41. Klengel T, Pape J, Binder EB, Mehta D. The role of DNA methylation in stressrelated psychiatric disorders. Neuropharmacology 2014; 80C: 115-132.
42. Mehta D, Klengel T, Conneely KN, Smith AK, Altmann A, Pace TW et al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc Natl Acad Sci USA 2013; 110: 8302-8307.
43. Mehta D, Newport DJ, Frishman G, Kraus L, Rex-Haffner M, Ritchie JC et al. Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling. Psychol Med 2014; 5: 1-14.
44. Lee RS, Tamashiro KLK, Yang X, Purcell RH, Harvey A, Willour VL et al. Chronic corticosterone exposure increases expression and decreases deoxyribonucleic acid methylation of Fkbp5 in mice. Endocrinology 2010; 151: 4332-4343.
45. Szyf M, Bick J. DNA methylation: a mechanism for embedding early life experiences in the genome. Child Dev 2013; 84: 49-57.
46. De Boever P, Wens B, Forcheh AC, Reynders H, Nelen V, Kleinjans J et al. Characterization of the peripheral blood transcriptome in a repeated measures design using a panel of healthy individuals. Genomics 2014; 103: 31-39.
47. Eady JJ, Wortley GM, Wormstone YM, Hughes JC, Astley SB, Foxall RJ et al. Variation in gene expression profiles of peripheral blood mononuclear cells from healthy volunteers. Physiol Genomics 2005; 22: 402-411. (Pubitemid 41356372)
48. Margraf J. Entstehung und Handhabung des Mini-DIPS. Springer: Berlin Heidelberg, 1994.
49. Hellhammer D, Hero T, Gerhards F, Hellhammer J. Neuropattern: a new translational tool to detect and treat stress pathology I. Strategical consideration. Stress 2012; 15: 479-487.
50. Hero T, Gerhards F, Thiart H, Hellhammer DH, Linden M. Neuropattern: a new translational tool to detect and treat stress pathology. II. The Teltow study. Stress 2012; 15: 488-494.
51. Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T et al. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl 2003; 27: 169-190. (Pubitemid 36293325)
52. Wingenfeld K, Spitzer C, Mensebach C, Grabe HJ, Hill A, Gast U et al. [The German version of the Childhood Trauma Questionnaire (CTQ): preliminary psychometric properties]. Psychother Psychosom Med Psychol 2010; 60: 442-450.
53. Wolfe J, Kimerling R. Gender issues in the assessment of posttraumatic stress disorder. In Wilson J, Keane TM (eds). Assessing Psychological Trauma and PTSD, Guilford: New York, NY, USA, 1997, pp 192-238.
54. Ungerer O, Deter H-C, Fikentscher E, Konzag TA. Verbesserte diagnostik von traumafolgestörungen durch den einsatz der life-stressor checklist. Psychother Psych Med 2010; 60: 434-441.
55. Alexander N, Kuepper Y, Schmitz A, Osinsky R, Kozyra E, Hennig J. Gene-environment interactions predict cortisol responses after acute stress: Implications for the etiology of depression. Psychoneuroendocrinology 2009; 34: 1294-1303.
56. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-CT method. Methods 2001; 25: 402-408. (Pubitemid 34164012)
57. Pinheiro J, Bates DM. Mixed Effects Models in S and S-Plus. Springer: New York, NY, USA, 2000.
58. Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 2003; 28: 916-931. (Pubitemid 36936799)
59. Preacher KJ, Kelley K. Effect size measures for mediation models: quantitative strategies for communicating indirect effects. Psychol Methods 2011; 16: 93-115.
60. Ulrich CM, Toriola AT, Koepl LM, Sandifer T, Poole EM, Duggan C et al. Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women. Epigenetics 2012; 7: 1020-1028.
61. McQueen JK, Wilson H, Sumner BE, Fink G. Serotonin transporter (SERT) mRNA and binding site densities in male rat brain affected by sex steroids. Brain Res Mol Brain Res 1999; 63: 241-247. (Pubitemid 29036974)
62. Willeit M, Praschak-Rieder N. Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: a review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry. NeuroImage 2010; 53: 878-892.
63. Baudry A, Mouillet-Richard S, Schneider B, Launay J-M, Kellermann O. miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science 2010; 329: 1537-1541.
64. Millan MJ. MicroRNA in the regulation and expression of serotonergic transmission in the brain and other tissues. Curr Opin Pharmacol 2011; 11: 11-22.
65. Moya PR, Wendland JR, Salemme J, Fried RL, Murphy DL. miR-15a and miR-16 regulate serotonin transporter expression in human placental and rat brain raphe cells. Int J Neuropsychopharm 2013; 16: 621-629.
66. Ichise M. Effects of early life stress on [11C]DASB positron emission tomography imaging of serotonin transporters in adolescent peer-and mother-reared Rhesus monkeys. J Neurosci 2006; 26: 4638-4643. (Pubitemid 44315364)
67. Heim C, Binder EB. Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Exp Neurol 2012; 233: 102-111.
68. Booij L, Wang D, Levesque ML, Tremblay RE, Szyf M. Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress-diathesis model of depression. Phil Trans R Soc B Biol Sci 2013; 368: 20120251-20120251.
69. Devlin AM, Brain U, Austin J, Oberlander TF. Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth. PLoS ONE 2010; 5: e12201.
70. van Eijk KR, De Jong S, Boks MP, Langeveld T, Colas F, Veldink JH et al. Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects. BMC Genomics 2012; 13: 1-1.
71. Sullivan PF, Fan C, Perou CM. Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 261-268.
72. Byun H, Siegmund K, Pan F. Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue-and individual-specific DNA methylation patterns. Hum Mol Genet 2009; 18: 4808-4817.
73. Wang D, Szyf M, Benkelfat C, Provençal N, Turecki G, Caramaschi D et al. Peripheral SLC6A4 DNA methylation is associated with in vivo measures of human brain serotonin synthesis and childhood physical aggression. PLoS ONE 2012; 7: e39501.
74. Åberg K, van den Oord EJCG. Epstein-Barr virus transformed DNA as a source of false positive findings in methylation studies of psychiatric conditions. Biol Psychiatry 2011; 70: e25-e26.
75. Parsey RV, Hastings RS, Oquendo MA, Hu X, Goldman D, Huang Y-Y et al. 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 2006; 163: 48-51. (Pubitemid 43050102)
76. Tsao C-W, Lin Y-S, Chen C-C, Bai C-H, Wu S-R. Cytokines and serotonin transporter in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 899-905. (Pubitemid 43795377)
77. Cannon DM, Ichise M, Rollis D, Klaver JM, Gandhi SK, Charney DS et al. Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder. Biol Psychiatry 2007; 62: 870-877. (Pubitemid 47488222)
78. Miller JM, Oquendo MA, Ogden RT, Mann JJ, Parsey RV. Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder. J Psychiatr Res 2008; 42: 1137-1144.
79. Belzeaux R, Formisano-Tréziny C, Loundou A, Boyer L, Gabert J, Samuelian J-C et al. Clinical variations modulate patterns of gene expression and define blood biomarkers in major depression. J Psychiatr Res 2010; 44: 1205-1213.
80. Kessler RC, Birnbaum H, Bromet E, Hwang I, Sampson N, Shahly V. Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychol Med 2010; 40: 225-237.