An epigenome-wide DNA methylation study of PTSD and depression in World Trade Center responders

Translational Psychiatry

Volumn 7, Issue 6, 2017, Pages

  Kuan, P F ^a   Waszczuk, M A ^b   Kotov, R ^b   Marsit, C J ^c   Guffanti, G ^d   Gonzalez, A ^b   Yang, X ^b   Koenen, K ^e   Bromet, E ^b   Luft, B J ^b  

^a Stony Brook University   (United States)

^b STONY BROOK UNIVERSITY   (United States)

^c EMORY UNIVERSITY   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CPG ISLAND; DNA METHYLATION; EPIGENETICS; GENETIC EPIGENESIS; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HUMAN; MAJOR DEPRESSION; MALE; MIDDLE AGED; POSTTRAUMATIC STRESS DISORDER; RESCUE PERSONNEL; SIGNAL TRANSDUCTION; TERRORISM;

CPG ISLANDS; DEPRESSIVE DISORDER, MAJOR; DNA METHYLATION; EMERGENCY RESPONDERS; EPIGENESIS, GENETIC; EPIGENOMICS; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MALE; MIDDLE AGED; SEPTEMBER 11 TERRORIST ATTACKS; SIGNAL TRANSDUCTION; STRESS DISORDERS, POST-TRAUMATIC;

EID: 85038372305     PISSN: None     EISSN: 21583188     Source Type: Journal    
DOI: 10.1038/TP.2017.130     Document Type: Article

References (78)

1. Smith TC, Ryan MA, Wingard DL, Slymen DJ, Sallis JF, Kritz-Silverstein D et al. New onset and persistent symptoms of post-traumatic stress disorder self reported after deployment and combat exposures: prospective population based US military cohort study. BMJ 2008; 336: 366–371.
2. Wells TS, LeardMann CA, Fortuna SO, Smith B, Smith TC, Ryan MA et al. A prospective study of depression following combat deployment in support of the wars in Iraq and Afghanistan. Am J Public Health. 2010; 100: 90–99.
3. Wisnivesky JP, Teitelbaum SL, Todd AC, Boffetta P, Crane M, Crowley L et al. Persistence of multiple illnesses in World Trade Center rescue and recovery workers: a cohort study. Lancet 2011; 378: 888–897.
4. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62: 593–602.
5. O'Donnell ML, Creamer M, Pattison P. Posttraumatic stress disorder and depression following trauma: understanding comorbidity. Am J Psychiatry. 2004; 161: 1390–1396.
6. Heinzelmann M, Gill J. Epigenetic mechanisms shape the biological response to trauma and risk for PTSD: a critical review. Nurs Res Pract 2013; 2013: 417010.
7. Schmidt U, Kaltwasser SF, Wotjak CT. Biomarkers in posttraumatic stress disorder: Overview and implications for future research. Dis Markers 2013; 35: 43–54.
8. Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S, Seckl JR et al. Epigenetic programming by maternal behavior. Nat Neurosci 2004; 7: 847–854.
9. 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.
10. McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonté B, Szyf M et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 2009; 12: 342–348.
11. Yehuda R, Flory JD, Bierer LM, Henn-Haase C, Lehrner A, Desarnaud F et al. Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry 2015; 77: 356–364.
12. Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008; 299: 1291–1305.
13. Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 2013; 16: 33–41.
14. Chang S-C, Koenen KC, Galea S, Aiello AE, Soliven R, Wildman DE et al. Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit Neighborhood Health Study. PLoS ONE 2012; 7: e39184.
15. Koenen KC, Uddin M, Chang SC, Aiello AE, Wildman DE, Goldmann E et al. SLC6A4 methylation modifies the effect of the number of traumatic events on risk for posttraumatic stress disorder. Depress Anxiety 2011; 28: 639–647.
16. Roth TL, Lubin FD, Funk AJ, Sweatt JD. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry 2009; 65: 760–769.
17. Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 2011; 470: 492–497.
18. Na K-S, Chang HS, Won E, Han K-M, Choi S, Tae WS et al. Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PLoS ONE 2014; 9: e85425.
19. Oberlander TF, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin AM. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 2008; 3: 97–106.
20. Olsson C, Foley D, Parkinson-Bates M, Byrnes G, McKenzie M, Patton G 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.
21. 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 B Neuropsychiatr Genet 2008; 147: 543–549.
22. Smart C, Strathdee G, Watson S, Murgatroyd C, McAllister-Williams R. Early life trauma, depression and the glucocorticoid receptor gene–an epigenetic per-spective. Psychol Med 2015; 45: 3393–3410.
23. Koenen KC, Duncan LE, Liberzon I, Ressler KJ. From candidate genes to genome-wide association: The challenges and promise of posttraumatic stress disorder genetic studies. Biol Psychiatry 2013; 74: 634.
24. Rakyan VK, Down TA, Balding DJ, Beck S. Epigenome-wide association studies for common human diseases. Nat Rev Genet 2011; 12: 529–541.
25. Uddin M, Aiello AE, Wildman DE, Koenen KC, Pawelec G, de Los Santos R et al. Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proc Natl Acad Sci USA 2010; 107: 9470–9475.
26. Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, Bradley B et al. Differential immune system DNA methylation and cytokine regulation in post‐traumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet 2011; 156: 700–708.
27. 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.
28. Vinkers CH, Kalafateli AL, Rutten BP, Kas MJ, Kaminsky Z, Turner JD et al. Traumatic stress and human DNA methylation: a critical review. Epigenomics 2015; 7: 593–608.
29. Zannas AS, Provençal N, Binder EB. Epigenetics of posttraumatic stress disorder: current evidence, challenges, and future directions. Biol Psychiatry 2015; 78: 327–335.
30. Januar V, Saffery R, Ryan J. Epigenetics and depressive disorders: a review of current progress and future directions. Int J Epidemiol 2015; 44: 1364–1387, dyu273.
31. Nagy C, Suderman M, Yang J, Szyf M, Mechawar N, Ernst C et al. Astrocytic abnormalities and global DNA methylation patterns in depression and suicide. Mol Psychiatry 2015; 20: 320–328.
32. Weder N, Zhang H, Jensen K, Yang BZ, Simen A, Jackowski A et al. Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. J Am Acad Child Adolesc Psychiatry 2014; 53: 417–424, e5.
33. Davies MN, Krause L, Bell JT, Gao F, Ward KJ, Wu H et al. Hypermethylation in the ZBTB20 gene is associated with major depressive disorder. Genome Biol 2014; 15: 1.
34. Dempster EL, Wong CC, Lester KJ, Burrage J, Gregory AM, Mill J et al. Genome-wide methylomic analysis of monozygotic twins discordant for adolescent depression. Biol Psychiatry 2014; 76: 977–983.
35. Sabunciyan S, Aryee MJ, Irizarry RA, Rongione M, Webster MJ, Kaufman WE et al. Genome-wide DNA methylation scan in major depressive disorder. PLoS ONE 2012; 7: e34451.
36. Byrne E, Carrillo-Roa T, Henders A, Bowdler L, McRae A, Heath A et al. Monozygotic twins affected with major depressive disorder have greater variance in methy-lation than their unaffected co-twin. Transl Psychiatry 2013; 3: e269.
37. Uddin M, Koenen K, Aiello AE, Wildman D, de Los Santos R, Galea S. Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample. Psychol Med 2011; 41: 997–1007.
38. Hammen C. Stress and depression. Annu Rev Clin Psychol. 2005; 1: 293–319.
39. Monroe SM, Simons AD. Diathesis-stress theories in the context of life stress research: implications for the depressive disorders. Psychol Bull 1991; 110: 406–425.
40. Houseman EA, Accomando WP, Koestler DC, Christensen BC, Marsit CJ, Nelson HH et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics 2012; 13: 1.
41. Reinius LE, Acevedo N, Joerink M, Pershagen G, Dahlén S-E, Greco D et al. Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility. PLoS ONE 2012; 7: e41361.
42. Herbert R, Moline J, Skloot G, Metzger K, Baron S, Luft B et al. The World Trade Center disaster and the health of workers: five-year assessment of a unique medical screening program. Environ Health Perspect 2006; 1853–1858.
43. First MB, Spitzer RL, Gibbon M, Williams JB. Structured Clinical Interview for DSM-IV Axis I Disorders: Patient Edition (February 1996 Final), SCID-I/P: Biometrics Research Department. New York State Psychiatric Institute: New York, NY, 1998.
44. Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D et al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics 2013; 29: 189–196.
45. Chen Y-a, Lemire M, Choufani S, Butcher DT, Grafodatskaya D, Zanke BW et al. Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray. Epigenetics 2013; 8: 203–209.
46. Price EM, Cotton AM, Lam LL, Farré P, Emberly E, Brown CJ et al. Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array. Epigenet Chromatin 2013; 6: 1.
47. Houseman EA, Kim S, Kelsey KT, Wiencke JK. DNA methylation in whole blood: uses and challenges. Curr Environ Health Rep 2015; 2: 145–154.
48. Barfield RT, Almli LM, Kilaru V, Smith AK, Mercer KB, Duncan R et al. Accounting for population stratification in DNA methylation studies. Genet Epidemiol 2014; 38: 231–241.
49. Du P, Zhang X, Huang CC, Jafari N, Kibbe WA, Hou L et al. Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinformatics 2010; 11: 587.
50. Kuan PF, Wang S, Zhou X, Chu H. A statistical framework for Illumina DNA methylation arrays. Bioinformatics 2010; 26: 2849–2855.
51. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 1995; 51: 289–300.
52. Phipson B, Maksimovic J, Oshlack A. missMethyl: an R package for analyzing data from Illumina's HumanMethylation450 platform. Bioinformatics 2016; 32:286–288.
53. Geeleher P, Hartnett L, Egan LJ, Golden A, Raja Ali RA, Seoighe C. Gene-set analysis is severely biased when applied to genome-wide methylation data. Bioinformatics 2013; 29: 1851–1857.
54. Young MD, Wakefield MJ, Smyth GK, Oshlack A. Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol. 2010; 11: R14.
55. 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. Progress Neuropsychopharmacol Biol Psychiatry 2013; 44: 23–28.
56. Perroud N, Paoloni-Giacobino A, Prada P, Olié E, Salzmann A, Nicastro R et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry 2011; 1: e59.
57. Uddin M, Sipahi L, Li J, Koenen KC. Sex differences in DNA methylation may contribute to risk of PTSD and depression: a review of existing evidence. Depress Anxiety 2013; 30: 1151–1160.
58. Harald B, Gordon P. Meta-review of depressive subtyping models. J Affect Disord 2012; 139: 126–140.
59. Heim C, Mletzko T, Purselle D, Musselman DL, Nemeroff CB. The dexamethasone/ corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biol Psychiatry. 2008; 63: 398–405.
60. Heim C, Newport DJ, Mletzko T, Miller AH, Nemeroff CB. The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology 2008; 33: 693–710.
61. Ota KT, Pierre VJ, Ploski JE, Queen K, Schafe GE. The NO-cGMP-PKG signaling pathway regulates synaptic plasticity and fear memory consolidation in the lateral amygdala via activation of ERK/MAP kinase. Learn Mem 2008; 15: 792–805.
62. Neumann ID, Slattery DA. Oxytocin in general anxiety and social fear: a translational approach. Biol Psychiatry. 2016; 79: 213–221.
63. Eidelman-Rothman M, Goldstein A, Levy J, Weisman O, Schneiderman I, Mankuta D et al. Oxytocin affects spontaneous neural oscillations in trauma-exposed war veterans. Front Behav Neurosci 2015; 9: 165.
64. Seng JS. Posttraumatic oxytocin dysregulation: is it a link among posttraumatic self disorders, posttraumatic stress disorder, and pelvic visceral dysregulation conditions in women? J Trauma Dissoc 2010; 11: 387–406.
65. Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in fear-and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsycho-pharmacology 2017; 42: 254–270.
66. Passos IC, Vasconcelos-Moreno MP, Costa LG, Kunz M, Brietzke E, Quevedo J et al. Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry 2015; 2: 1002–1012.
67. Rosen RL, Levy-Carrick N, Reibman J, Xu N, Shao Y, Liu M et al. Elevated C-reactive protein and posttraumatic stress pathology among survivors of the 9/11 World Trade Center attacks. J Psychiatr Res. 2017; 89: 14–21.
68. Mahon PB, Zandi PP, Potash JB, Nestadt G, Wand GS. Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults. Psychopharmacology (Berl) 2013; 227: 231–241.
69. Yehuda R, Cai G, Golier JA, Sarapas C, Galea S, Ising M et al. Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks. Biol Psychiatry 2009; 66: 708–711.
70. Scott KM, Lim C, Al-Hamzawi A, Alonso J, Bruffaerts R, Caldas-de-Almeida JM et al. Association of mental disorders with subsequent chronic physical conditions: world mental health surveys from 17 countries. JAMA Psychiatry 2016; 73: 150–158.
71. Swartzman S, Booth JN, Munro A, Sani F. Posttraumatic stress disorder after cancer diagnosis in adults: a meta-analysis. Depress Anxiety. 2016; 34: 327–339.
72. Ahmadi N, Arora R, Vaidya N, Yehuda R, Ebrahimi R. Post-traumatic stress disorder is associated with increased incidence of insulin resistance and metabolic syn-drome. J Am Coll Cardiol 2013; 61: E1347.
73. Donati RJ, Rasenick MM. G protein signaling and the molecular basis of antidepressant action. Life Sci. 2003; 73: 1–17.
74. Harwood AJ. Lithium and bipolar mood disorder: the inositol-depletion hypoth-esis revisited. Mol Psychiatry. 2005; 10: 117–126.
75. Racagni G, Popoli M. Cellular and molecular mechanisms in the long-term action of antidepressants. Dialogues Clin Neurosci 2008; 10: 385–400.
76. Xu X, Muller-Taubenberger A, Adley KE, Pawolleck N, Lee VW, Wiedemann C et al. Attenuation of phospholipid signaling provides a novel mechanism for the action of valproic acid. Eukaryot Cell. 2007; 6: 899–906.
77. Aberg KA, McClay JL, Nerella S, Clark S, Kumar G, Chen W et al. Methylome-wide association study of schizophrenia: identifying blood biomarker signatures of environmental insults. JAMA Psychiatry 2014; 71: 255–264.
78. Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol 2013; 31: 142–147.