期刊论文详细信息
Biology of Mood & Anxiety Disorders
Considering trauma exposure in the context of genetics studies of posttraumatic stress disorder: a systematic review
Julia DiGangi1  Guia Guffanti2  Katie A McLaughlin4  Karestan C Koenen3 
[1] DePaul University, Chicago, IL, USA
[2] Department of Psychiatry, Columbia University/New York State Psychiatric Institute, New York, NY, USA
[3] Department of Epidemiology, Mailman School of Public Health, New York, NY, USA
[4] Division of General Pediatrics, Department of Psychiatry, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
关键词: Gene–environment interaction;    Genome-wide association studies;    Genetics;    Trauma;    Posttraumatic stress disorder;   
Others  :  792034
DOI  :  10.1186/2045-5380-3-2
 received in 2012-08-09, accepted in 2012-10-22,  发布年份 2013
PDF
【 摘 要 】

Background

Posttraumatic stress disorder (PTSD) is a debilitating anxiety disorder. Surveys of the general population suggest that while 50-85% of Americans will experience a traumatic event in their lifetime, only 2-50% will develop PTSD. Why some individuals develop PTSD following trauma exposure while others remain resilient is a central question in the field of trauma research. For more than half a century, the role of genetic influences on PTSD has been considered as a potential vulnerability factor. However, despite the exponential growth of molecular genetic studies over the past decade, limited progress has been made in identifying true genetic variants for PTSD.

Methods

In an attempt to aid future genome wide association studies (GWAS), this paper presents a systematic review of 28 genetic association studies of PTSD. Inclusion criteria required that 1) all participants were exposed to Criterion A traumatic events, 2) polymorphisms of relevant genes were genotyped and assessed in relation to participants’ PTSD status, 3) quantitative methods were used, and 4) articles were published in English and in peer-reviewed journals. In the examination of these 28 studies, particular attention was given to variables related to trauma exposure (e.g. number of traumas, type of trauma).

Results

Results indicated that most articles did not report on the GxE interaction in the context of PTSD or present data on the main effects of E despite having data available. Furthermore, some studies that did consider the GxE interaction had significant findings, underscoring the importance of examining how genotypes can modify the effect of trauma on PTSD. Additionally, results indicated that only a small number of genes continue to be studied and that there were marked differences in methodologies across studies, which subsequently limited robust conclusions.

Conclusions

As trauma exposure is a necessary condition for the PTSD diagnosis, this paper identifies gaps in the current literature as well as provides recommendations for how future GWAS studies can most effectively incorporate trauma exposure data in both the design and analysis phases of studies.

【 授权许可】

   
2013 DiGangi et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140705023633314.pdf 355KB PDF download
Figure 3. 67KB Image download
Figure 2. 43KB Image download
Figure 1. 44KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】
  • [1]American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th edition. Washington, D.C: Author; 1994.
  • [2]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(6):593-602.
  • [3]Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB: Posttraumatic stress disorder in the national comorbidity survey. Arch Gen Psychiatry 1995, 52:1048-1060.
  • [4]Roberts AL, Gilman SE, Breslau J, Breslau N, Koenen KC: Race/ethnic differences in exposure to traumatic events, development of post-traumatic stress disorder, and treatment-seeking for post-traumatic stress disorder in the United States. Psychol Med 2011, 41(1):71-83.
  • [5]Roberts AL, Austin SB, Corliss HL, Vandermorris AK, Koenen KC: Pervasive trauma exposure among US sexual orientation minority adults and risk of posttraumatic stress disorder. Am J Public Health 2010, 100(12):2433-2441.
  • [6]Slater E, Slater P: A heuristic theory of neurosis, in Man, mind & heredity: selected papers of Eliot Slater on psychiatry and genetics. Edited by Sheilds J, Gottesman II. Baltimore: Johns Hopkins Press; 1944:216-227.
  • [7]Sartor CE, McCutcheon VV, Pommer NE, Nelson EC, Grant JD, Duncan AE, Waldron M, Bucholz KK, Madden PA, Heath AC: Common genetic and environmental contributions to post-traumatic stress disorder and alcohol dependence in young women. Psychol Med 2011, 41(7):1497-1505.
  • [8]Stein MB, Jang KJ, Livesley J: Heritability of anxiety sensitivity: a twin study. Am J Psychiatry 1999, 156:246-251.
  • [9]True WJ, Rice J, Eisen SA, Heath AC, Goldberg J, Lyons MJ, Nowak J: A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Arch Gen Psychiatry 1993, 50:257-264.
  • [10]Comings DE, Comings BG, Muhleman D, Dietz G, Shabbahrami B, Tast D: The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorder. JAMA 1991, 266:1793-1800.
  • [11]Cornelis MC, Nugent NR, Amstadter AB, Koenen KC: Genetics of post-traumatic stress disorder: review and recommendations for genome-wide association studies. Curr Psychiatry Rep 2010, 12(4):313-326.
  • [12]Mukherjee B, Ahn J, Gruber SB, Chatterjee N: Testing gene-environment interaction in large-scale case–control association studies: possible choices and comparisons. Am J Epidemiol 2012, 175(3):177-190.
  • [13]Deng WQ, Paré G: A fast algorithm to optimize SNP prioritization for gene-gene and gene-environment interactions. Genet Epidemiol 2011, 35(7):729-738.
  • [14]Thomas D: Gene–environment-wide association studies: emerging approaches. Nat Rev Genet 2010, 11(4):259-272.
  • [15]Muglia P, Tozzi F, Galwey NW, Francks C, Upmanyu R, Kong XQ, Antoniades A, Domenici E, Perry J, Rothen S, Vandeleur CL, Mooser V, Waeber G, Vollenweider P, Preisig M, Lucae S, Muller-Myhsok B, Holsboer F, Middleton LT, Roses AD: Genome-wide association study of recurrent major depressive disorder in two European case–control cohorts. Mol Psychiatry 2010, 15:589-601.
  • [16]Van den Oord EJ, Kuo PH, Hartmann AM, Webb BT, Moller HJ, Hettema JM, Giegling I, Bukszar J, Rujescu D: Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism. Arch Gen Psychiatry 2008, 65(9):1062-1071.
  • [17]Sullivan PF, de Geus EJC, Willemsen G, James MR, Smit JH, Zandbelt T, Arolt V, Baune BT, Blackwood D, Cichon S, Coventry WL, Domschke K, Farmer A, Fava M, Gordon SD, He Q, Heath AC, Heutink P, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hu Y, Kohli M, Lin D, Lucae S, MacIntyre DJ, Maier W, McGhee KA, McGuffin P, Montgomery GW, et al.: Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Mol Psychiatry 2008, 14(4):359-375.
  • [18]Shi J, Potash JB, Knowles JA, Weissman MM, Coryell W, Scheftner WA, Lawson WB, DePaulo JR Jr, Gejman PV, Sanders AR, Johnson JK, Adams P, Chaudhury S, Jancic D, Evgrafov O, Zvinyatskovskiy A, Ertman N, Gladis M, Neimanas K, Goodell M, Hale N, Ney N, Verma R, Mirel D, Holmans P, Levinson DF: Genome-wide association study of recurrent early-onset major depressive disorder. Mol Psychiatry 2011, 16(2):193-201.
  • [19]Shyn SI, Shi J, Kraft JB, Potash JB, Knowles JA, Weissman MM, Garriock HA, Yokoyama JS, McGrath PJ, Peters EJ, Scheftner WA, Coryell W, Lawson WB, Jancic D, Gejman PV, Sanders AR, Holmans P, Slager SL, Levinson DF, Hamilton SP: Novel loci for major depression identified by genome-wide association study of sequenced treatment alternatives to relieve depression and meta-analysis of three studies. Mol Psychiatry 2011, 16(2):202-215.
  • [20]Lewis CM, Ng MY, Butler AW, Cohen-Woods S, Uher R, Pirlo K, Weale ME, Schosser A, Paredes UM, Rivera M, Craddock N, Owen MJ, Jones L, Jones I, Korszun A, Aitchison KJ, Shi J, Quinn JP, MacKenzie A, Vollenweider P, Waeber G, Heath S, Lathrop M, Muglia P, Barnes MR, Whittaker JC, Tozzi F, Holsboer F, Preisig M, Farmer AE, et al.: Genome-wide association study of major recurrent depression in the U.K. population. Am J Psychiatry 2010, 167(8):949-957.
  • [21]Wray NR, Pergadia ML, Blackwood DHR, Penninx BWJH, Gordon SD, Nyholt DR, Ripke S, MacIntyre DJ, McGhee KA, Maclean AW, Smit JH, Hottenga JJ, Willemsen G, Middeldorp CM, de Geus EJC, Lewis CM, McGuffin P, Hickie IB, Van den Oord EJCG, Liu JZ, Macgregor S, McEvoy BP, Byrne EM, Medland SE, Statham DJ, Henders AK, Heath AC, Montgomery GW, Martin NG, Boomsma DI, et al.: Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned. Mol Psychiatry 2012, 17(1):36-48.
  • [22]Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR: Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 2009, 301(23):2462-2471.
  • [23]Consortium, M.D.D.W.G.o.t.P.G: A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry 2012.
  • [24]Breslau N, Kessler RC, Chilcoat HD, Schultz LR, Davis GC, Andreski P: Trauma and posttraumatic stress disorder in the community: the 1996 Detroit area survey of trauma. Arch Gen Psychiatry 1998, 55(7):626-632.
  • [25]McLaughlin KA, Conron KJ, Koenen KC, Gilman SE: Childhood adversity, adult stressful life events, and risk of past-year psychiatric disorder: a test of the stress sensitization hypothesis in a population-based sample of adults. Psychol Med 2009, 1-12.
  • [26]Keyes KM, McLaughlin KA, Koenen KC, Goldmann E, Uddin M, Galea S: Child maltreatment increases sensitivity to adverse social contexts: neighborhood physical disorder and incident binge drinking in Detroit. Drug Alcohol Depend 2011.
  • [27]Drury SS, Theall KP, Keats BJB, Scheeringa M: The role of the dopamine transporter (DAT) in the development of PTSD in preschool children. J Trauma Stress 2009, 22(6):534-539.
  • [28]Amstadter AB, Nugent NR, Yang B-Z, Miller A, Siburian R, Moorjani P, Haddad S, Basu A, Fagerness J, Saxe G, Smoller JW, Koenen KC: Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients. Dis Markers 2011, 30(2):89-99.
  • [29]Kilpatrick DG, Koenen KC, Ruggiero KJ, Acierno R, Galea S, Resnick HS, Roitzsch J, Boyle J, Gelernter J: The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. Am J Psychiatry 2007, 164(11):1693-1699.
  • [30]Amstadter AB, Koenen KC, Ruggiero KJ, Acierno R, Galea S, Kilpatrick DG, Gelernter J: Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure. J Anxiety Disord 2009, 23(3):369-373.
  • [31]Binder EB, Bradley RG, Liu W, Epstein M, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, Ressler KJ: Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008, 299(11):1291-1305.
  • [32]Xie P, Kranzler HR, Poling J, Stein MB, Anton RF, Farrer LA, Gelernter J: Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology 2010, 35(8):1684-1692.
  • [33]Sarapas C, Cai G, Bierer LM, Golier JA, Galea S, Ising M, Rein T, Schmeidler J, Müller-Myhsok B, Uhr M, Holsboer F, Buxbaum JD, Yehuda R: Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks. Dis Markers 2011, 30(2):101-110.
  • [34]Nugent NR, Amstadter AB, Koenen KC: Genetics of post-traumatic stress disorder: informing clinical conceptualizations and promoting future research. Am J Med Genet C Semin Med Genet 2008, 148C(2):127-132.
  • [35]Koenen KC, Nugent NR, Amstadter AB: Gene-environment interaction in posttraumatic stress disorder: review, strategy and new directions for future research. Eur Arch Psychiatry Clin Neurosci 2008, 258(2):82-96.
  • [36]Koenen KC, Amstadter AB, Nugent NR: Gene-environment interaction in posttraumatic stress disorder: an update. J Trauma Stress 2009, 22(5):416-426.
  • [37]Kremen WS, Koenen KC, Afari N, Lyons MJ: Twin studies of posttraumatic stress disorder: differentiating vulnerability factors from sequelae. Neuropharmacology 2012, 62(2):647-653.
  • [38]Broekman BF, Olff M, Boer F: The genetic background to PTSD. Neurosci Biobehav Rev 2007, 31(3):348-362.
  • [39]Segman RH, Shalev AY: Genetics of posttraumatic stress disorder. CNS Spectr 2003, 8(9):693-698.
  • [40]Thakur GA, Joober R, Brunet A: Development and persistence of posttraumatic stress disorder and the 5-HTTLPR polymorphism. J Trauma Stress 2009, 22(3):240-243.
  • [41]Bachmann AW, Sedgley TL, Jackson RV, Gibson JN, Young RM, Torpy DJ: Glucocorticoid receptor polymorphisms and post-traumatic stress disorder. Psychoneuroendocrinology 2005, 30(3):297-306.
  • [42]Comings DE, Muhleman D, Gysin R: Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: a study and replication. Biol Psychiatry 1996, 40(5):368-372.
  • [43]Gelernter J, Southwick S, Goodson S, Morgan A, Nagy L, Charney DS: No association between D2 dopamine receptor (DRD2) “A” system alleles, or DRD2 haplotypes, and posttraumatic stress disorder. Biol Psychiatry 1999, 45(5):620-625.
  • [44]Kolassa I-T: Association study of trauma load and SLC6A4 promoter polymorphism in posttraumatic stress disorder evidence from survivors of the Rwandan genocide. 2010.
  • [45]Segman RH, Cooper-Kazaz R, Macciardi F, Goltser T, Halfon Y, Dobroborski T, Shalev AY: Association between the dopamine transporter gene and posttraumatic stress disorder. Mol Psychiatry 2002, 7(8):903-907.
  • [46]Valente N, Vallada H, Cordeiro Q, Miguita K, Bressan R, Andreoli S, Mari J, Mello M: Candidate-gene approach in posttraumatic stress disorder after urban violence: association analysis of the genes encoding serotonin transporter, dopamine transporter, and BDNF. J Mol Neurosci 2011, 44(1):59-67.
  • [47]Hauer D, Weis F, Papassotiropoulos A, Schmoeckel M, Beiras-Fernandez A, Lieke J, Kaufmann I, Kirchhoff F, Vogeser M, Roozendaal B, Briegel J, de Quervain D, Schelling G: Relationship of a common polymorphism of the glucocorticoid receptor gene to traumatic memories and posttraumatic stress disorder in patients after intensive care therapy. Crit Care Med 2011, 39(4):643-650.
  • [48]Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, Norrholm SD, Kilaru V, Smith AK, Myers AJ, Ramirez M, Engel A, Hammack SE, Toufexis D, Braas KM, Binder EB, May V: Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 2011, 470(7335):492-497.
  • [49]Purcell SM, Wray R, Stone L, Visscher M, O'Donovan C, Sullivan F, Sklar P, Ruderfer M, McQuillin A, Morris W, O'Dushlaine T, Corvin A, Holmans A, Macgregor S, Gurling H, Blackwood R, Craddock J, Gill M, Hultman CM, Kirov K, Lichtenstein P, Muir J, Owen J, Pato N, Scolnick M, St Clair D, Williams M, Georgieva L, Nikolov I, Norton N, et al.: Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009, 460(7256):748-752.
  • [50]Califano A, Butte AJ, Friend S, Ideker T, Schadt E: Leveraging models of cell regulation and GWAS data in integrative network-based association studies. Nat Genet 2012, 44(8):841-847.
  • [51]Ozer EJ, Best SR, Lipsey TL, Weiss DS: Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. Psychol Bull 2003, 129(1):52-73.
  • [52]Dragan WL, Oniszczenko W: The association between dopamine D4 receptor exon III polymorphism and intensity of PTSD symptoms among flood survivors. Anxiety Stress Coping 2009, 22(5):483-495.
  • [53]Kolassa I-T, Kolassa S, Ertl V, Papassotiropoulos A, De Quervain DJF: The risk of posttraumatic stress disorder after trauma depends on traumatic load and the Catechol-O-Methyltransferase val158met polymorphism. Biol Psychiatry 2010, 67(4):304-308.
  • [54]Valente N, Vallada H, Cordeiro Q, Bressan R, Andreoli S, Mari J, Mello M: Catechol-O-methyltransferase (COMT) val158met polymorphism as a risk factor for PTSD after urban violence. J Mol Neurosci 2011, 43(3):516-523.
  • [55]Breslau N, Chilcoat HD, Kessler RC, Davis GC: Previous exposure to trauma and PTSD effects of subsequent trauma: results from the Detroit area survey of trauma. Am J Psychiatry 1999, 156(6):902-907.
  • [56]Nelson EC, Agrawal A, Pergadia ML, Lynskey MT, Todorov AA, Wang JC, Todd RD, Martin NG, Heath AC, Goate AM, Montgomery GW, Madden PAF: Association of childhood trauma exposure and GABRA2 polymorphisms with risk of posttraumatic stress disorder in adults. Mol Psychiatry 2009, 14(3):234-235.
  • [57]Xie P, Kranzler HR, Poling J, Stein MB, Anton RF, Brady K, Weiss RD, Farrer L, Gelernter J: Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. Arch Gen Psychiatry 2009, 66(11):1201-1209.
  • [58]Blanchard EB, Hickling EJ, Taylor AE, Loos WR, Gerardi RJ: Psychological morbidity associated with motor vehicle accidents. Behav Res Ther 1994, 32(3):283-290.
  • [59]Elhai JD, Frueh BC, Gold PB, Gold SN, Hamner MB: Clinical presentations of posttraumatic stress disorder across trauma populations: a comparison of MMPI-2 profiles of combat veterans and adult survivors of child sexual abuse. J Nerv Ment Dis 2000, 188(10):708-713.
  • [60]Bailey JN, Goenjian AK, Noble EP, Walling DP, Ritchie T, Goenjian HA: PTSD and dopaminergic genes, DRD2 and DAT, in multigenerational families exposed to the Spitak earthquake. Psychiatry Res 2010, 178(3):507-510.
  • [61]Hunter DJ: Gene-environment interactions in human diseases. Nat Rev Genet 2005, 6(4):287-298.
  • [62]Sayin A, Kucukyildirim S, Akar T, Bakkaloglu Z, Demircan A, Kurtoglu G, Demirel B, Candansayar S, Mergen H: A Prospective Study of Serotonin Transporter Gene Promoter (5-HTT Gene Linked Polymorphic Region) and Intron 2 (Variable Number of Tandem Repeats) Polymorphisms as Predictors of Trauma Response to Mild Physical Injury. DNA Cell Biol 2010, 29(2):71-77.
  • [63]Grabe HJ, Spitzer C, Schwahn C, Marcinek A, Frahnow A, Barnow S, Lucht M, Freyberger HJ, John U, Wallaschofski H, Völzke H, Rosskopf D: Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. Am J Psychiatry 2009, 166(8):926-933.
  • [64]Mellman TA, Alim T, Brown DD, Gorodetsky E, Buzas B, Lawson WB, Goldman D, Charney DS: Serotonin polymorphisms and posttraumatic stress disorder in a trauma exposed African American population. Depress Anxiety 2009, 26(11):993-997.
  • [65]Giles J: The trouble with replication. Nature 2006, 442(7101):344-347.
  文献评价指标  
  下载次数:41次 浏览次数:8次