Hostname: page-component-745bb68f8f-l4dxg Total loading time: 0 Render date: 2025-01-11T02:51:51.084Z Has data issue: false hasContentIssue false
  • English
  • Français

Combat exposure severity as a moderator of genetic and environmental liability to post-traumatic stress disorder

Published online by Cambridge University Press:  04 September 2013

E. J. Wolf ,
K. S. Mitchell ,
K. C. Koenen  and
M. W. Miller
E. J. Wolf*
Affiliation:
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA
K. S. Mitchell
Affiliation:
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA
K. C. Koenen
Affiliation:
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA
M. W. Miller
Affiliation:
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA
*
* Address for correspondence: E. J. Wolf, Ph.D., National Center for PTSD, VA Boston Healthcare System (116B-2), 150 South Huntington Avenue, Boston, MA 02130, USA. (Email: Erika.Wolf@va.gov)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Twin studies of veterans and adults suggest that approximately 30–46% of the variance in post-traumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to determine whether the effects of genetic and environmental factors that contribute to the etiology of PTSD are dependent on the level of combat exposure.

Method

The sample was drawn from the Vietnam Era Twin Registry (VETR) and included 620 male–male twin pairs who served in the US Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure.

Results

Biometric modeling revealed that the effects of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure.

Conclusions

Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations.

Keywords

Combat exposureG × Egeneticpost-traumatic stress disordertwins
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 7 , May 2014 , pp. 1499 - 1509
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akaike, H (1987). Factor analysis and the AIC. Psychometrika 52, 317–332.Google Scholar
Amstadter, AB, Koenen, KC, Ruggiero, KJ, Acierno, R, Galea, S, Kilpatrick, DG, Gelernter, J (2009). Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure. Journal of Anxiety Disorders 23, 369–373.Google Scholar
APA (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn, revised. American Psychiatric Association: Washington, DC.Google Scholar
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Bagout, RC, Meaney, MJ (2010). Epigenetics and the biological basis of gene × environment interactions. Journal of the American Academy of Child and Adolescent Psychiatry 49, 752–771.Google Scholar
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. Journal of the American Medical Association 299, 1291–1305.Google Scholar
Breslau, N, Chilcoat, HD, Kessler, RD, Davis, GC (1999). Previous exposure to trauma and PTSD effects of subsequent trauma: results from the Detroit area survey of trauma. American Journal of Psychiatry 156, 902–907.CrossRefGoogle ScholarPubMed
Breslau, N, Peterson, EL, Schultz, LR (2008). A second look at prior trauma and the posttraumatic stress disorder effects of subsequent trauma. Archives of General Psychiatry 65, 431–437.Google Scholar
Chang, S-C, Koenen, KC, Galea, S, Aiello, AE, Soliven, R, Wildman, DE, Uddin, M (2012). Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit Neighborhood Health Study. PLoS One 7, e39184.CrossRefGoogle ScholarPubMed
Distel, MA, Middeldorp, CM, Trull, TJ, Derom, CA, Willemsen, G, Boomsma, DI (2011). Life events and borderline personality features: the influence of gene-environment interaction and gene-environment correlation. Psychological Medicine 41, 849–860.Google Scholar
Dubois, L, Kyvik, KO, Girard, M, Tatone-Tokuda, F, Perusse, D, Hjelmborg, J, Skytthe, A, Rasmussen, F, Wright, MJ, Lichtenstein, P, Martin, NG (2012). Genetic and environmental contributions to weight, height, and BMI from birth to 19 years of age: an international study of over 12,000 twin pairs. PLoS One 7, e30153.Google Scholar
Eisen, S, Neuman, R, Goldberg, J, Rice, J, True, W (1989). Determining zygosity in the Vietnam Era Twin Registry: an approach using questionnaires. Clinical Genetics 35, 423–432.CrossRefGoogle ScholarPubMed
Gilbertson, MW, McFarlane, AC, Weathers, FW, Keane, TM, Yehuda, R, Shalev, AY, Lasko, NB, Goetz, JM, Pitman, RK (2010). Is trauma a causal agent of psychopathologic symptoms in posttraumatic stress disorder? Findings from identical twins discordant for combat exposure. Journal of Clinical Psychiatry 71, 1324–1330.CrossRefGoogle ScholarPubMed
Goldberg, J, True, WR, Eisen, SA, Henderson, WG (1990). A twin study of the effects of the Vietnam War on posttraumatic stress disorder. Journal of the American Medical Association 263, 1227–1232.Google Scholar
Hammen, C, Henry, R, Daley, SE (2000). Depression and sensitization to stressors among young women as a function of childhood adversity. Journal of Consulting and Clinical Psychology 68, 782–787.Google Scholar
Hicks, BM, South, SC, Dirago, AC, Iacono, WG, McGue, M (2009). Environmental adversity and increasing genetic risk for externalizing disorders. Archives of General Psychiatry 66, 640–648.Google Scholar
Janes, GR, Goldberg, J, Eisen, SA, True, WR (1991). Reliability and validity of a combat exposure index for Vietnam era veterans. Journal of Clinical Psychology 47, 80–86.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Jang, KL, Stein, MB, Taylor, S, Asmundson, GJ, Livesley, WJ (2003). Exposure to traumatic events and experiences: aetiological relationships with personality function. Psychiatry Research 120, 61–69.Google Scholar
Jang, KL, Taylor, S, Stein, MB, Yamagata, S (2007). Trauma exposure and stress response: exploration of mechanisms of cause and effect. Twin Research and Human Genetics 10, 564–572.Google Scholar
Kilpatrick, DG, Koenen, KC, Ruggiero, KJ, Acierno, R, Galea, S, Resnick, HS, Roitzsch, J, Boyle, J, Gelernter, J (2007). The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. American Journal of Psychiatry 164, 1693–1699.Google Scholar
Koenen, KC, Harley, R, Lyons, MJ, Wolfe, J, Simpson, JC, Goldberg, J, Eisen, S, Tsuang, M (2002). A twin registry study of familial and individual risk factors for trauma exposure and posttraumatic stress disorder. Journal of Nervous and Mental Disease 190, 209–218.Google Scholar
Koenen, KC, Lyons, MJ, Goldberg, J, Simpson, J, Williams, WM, Toorney, R, Eisen, SA, True, WR, Cloitre, M, Wolfe, J, Tsuang, MT (2003). A high risk twin study of combat-related PTSD comorbidity. Twin Research 6, 218–226.Google Scholar
Koenen, KC, Uddin, M, Chang, S-C, Aiello, AE, Wildman, DE, Goldmann, E, Galea, S (2011). SLC6A4 methylation modifies the effect of the number of traumatic events on risk for posttraumatic stress disorder. Depression and Anxiety 28, 639–647.Google Scholar
Kolassa, I-T, Kolassa, S, Ertl, V, Papassotiropoulos, A, De Quervain, DJ-F (2010). The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-O-methyltransferase Val158Met polymorphism. Biological Psychiatry 67, 304–308.CrossRefGoogle Scholar
Lyons, MJ, Eisen, SA, Goldberg, J, True, W, Lin, N, Meyer, JM, Toomey, R, Faraone, SV, Merla-Ramos, M, Tsuang, MT (1998). A registry-based twin study of depression in men. Archives of General Psychiatry 55, 468–472.CrossRefGoogle ScholarPubMed
MacCallum, RC, Widaman, KF, Zhang, S, Hong, S (1999). Sample size in factor analysis. Psychological Methods 4, 84–99.Google Scholar
McLaughlin, KA, Conron, KJ, Koenen, KC, Gilman, SE (2010). 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. Psychological Medicine 40, 1647–1658.CrossRefGoogle Scholar
McLeod, DS, Koenen, KC, Meyer, JM, Lyons, MJ, Eisen, S, True, W, Goldberg, J (2001). Genetic and environmental influences on the relationship among combat exposure, posttraumatic stress disorder symptoms, and alcohol use. Journal of Traumatic Stress 14, 259–275.CrossRefGoogle ScholarPubMed
Moffitt, TE, Caspi, A, Rutter, M (2005). Strategy for investigating interactions between measured genes and measured environments. Archives of General Psychiatry 62, 473–481.Google Scholar
Muthén, LK, Muthén, BO (2012). Mplus User's Guide. Seventh Edition. Muthén & Muthén: Los Angeles, CA.Google Scholar
Nelson, EC, Agrawal, A, Pergadia, ML, Lynskey, MT, Todorov, AA, Wang, JC, Todd, RD, Martin, NG, Heath, AC, Goate, AM, Montgomery, GW, Madden, PAF (2009). Association of childhood trauma exposure and GABRA2 polymorphisms with risk of posttraumatic stress disorder in adults. Molecular Psychiatry 14, 234–235.CrossRefGoogle ScholarPubMed
Plomin, R, DeFries, JC, Loehlin, JC (1977). Genotype-environment interaction and correlation in the analysis of human behavior. Psychological Bulletin 84, 309–322.Google Scholar
Purcell, S (2002). Variance components models for gene-environment interaction in twin analysis. Twin Research 5, 554–571.Google Scholar
Rathouz, PJ, van Hulle, CA, Rodgers, JL, Waldman, ID, Lahey, BB (2008). Specification, testing, and interpretation of gene-by-measured-environment interaction models in the presence of gene-environment correlation. Behavior Genetics 38, 301–315.Google Scholar
Robins, LN, Helzer, JE, Cottler, L, Golding, E (1998). National Institute of Mental Health Diagnostic Interview Schedule, Version III – Revised. Department of Psychiatry, Washington University in St Louis: St Louis, MO.Google Scholar
Roy-Byrne, P, Arguelles, L, Vitek, ME, Goldberg, J, Keane, TM, True, WR, Pitman, RK (2004). Persistence and change of PTSD symptomatology – a longitudinal co-twin control analysis of the Vietnam Era Twin Registry. Social Psychiatry and Psychiatric Epidemiology 39, 681–685.CrossRefGoogle ScholarPubMed
Sartor, CE, Grant, JD, Lynskey, MT, McCutcheon, VV, Waldron, M, Statham, DJ, Bucholz, KK, Madden, PAF, Heath, AC, Martin, NG, Nelson, EC (2012). Common heritable contributions to low-risk trauma, high-risk trauma, posttraumatic stress disorder, and major depression. Archives of General Psychiatry 69, 293–299.Google Scholar
Sartor, CE, McCutcheon, VV, Pommer, NE, Nelson, EC, Grant, JD, Duncan, AE, Waldron, M, Bucholz, KK, Madden, PAF, Heath, AC (2011). Common genetic and environmental contributions to post-traumatic stress disorder and alcohol dependence in young women. Psychological Medicine 41, 1497–1505.Google Scholar
Scherrer, JF, Xian, H, Lyons, MJ, Goldberg, J, Eisen, SA, True, WR, Tsuang, MT, Bucholz, KK, Koenen, KC (2008). Posttraumatic stress disorder; combat exposure; and nicotine dependence, alcohol dependence, and major depression in male twins. Comprehensive Psychiatry 49, 297–304.CrossRefGoogle ScholarPubMed
Schwartz, G (1978). Estimating the dimension of a model. Annals of Statistics 6, 461–464.Google Scholar
Silventoinen, K (2003). Determinants of variation in adult body height. Journal of Biosocial Science 35, 263–285.Google Scholar
Smith, AK, Conneely, KN, Kilaru, V, Mercer, KB, Weiss, TE, Bradley, B, Tang, Y, Gillespie, CF, Cubells, JF, Ressler, KJ (2011). Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 156, 700–708.Google Scholar
South, SC, Krueger, RF (2011). Genetic and environmental influences on internalizing psychopathology vary as a function of economic status. Psychological Medicine 41, 107–117.CrossRefGoogle ScholarPubMed
Stein, MB, Jang, KJ, Taylor, S, Vernon, PA, Livesley, WJ (2002). Genetic and environmental influences on trauma exposure and posttraumatic stress disorder: a twin study. American Journal of Psychiatry 159, 1675–1681.Google Scholar
True, WJ, Rice, J, Eisen, SA, Heath, AC, Goldberg, J, Lyons, MJ, Nowak, J (1993). A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Archives of General Psychiatry 50, 257–264.Google Scholar
Tsai, M, Mori, AM, Forsberg, CW, Waiss, N, Sporleder, JL, Smith, NL, Goldberg, J (2012). The Vietnam Era Twin Registry: a quarter century of progress. Twin Research and Human Genetics 16, 429–436.Google Scholar
Tsuang, MT, Lyons, MJ, Eisen, SA, Goldberg, J, True, WR, Lin, N, Meyer, JM, Toomey, R, Faraone, SV, Eaves, L (1996). Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 67, 473–477.Google Scholar
Turkheimer, E, Haley, A, Waldron, M, D'Onorio, B, Gottesman, II (2003). Socioeconomic status modifies heritability of IQ in young children. Psychological Science 14, 623–628.CrossRefGoogle ScholarPubMed
Uddin, M, Aiello, AE, Wildman, DE, Koenen, KC, Pawelec, G, de los Santos, R, Goldmann, E, Galea, S (2010). Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proceedings of the National Academy of Sciences USA 107, 9470–9475.Google Scholar
Uddin, M, Galea, S, Chang, S-C, Aiello, AE, Wildman, DE, de los Santos, R, Koenen, KC (2011). Gene expression and methylation signatures of MAN2C1 are associated with PTSD. Disease Markers 30, 111–121.Google Scholar
van der Sluis, S, Posthuma, D, Dolan, CV (2012). A note on false positives and power in G × E modelling of twin data. Behavior Genetics 42, 170–86.CrossRefGoogle Scholar
van Hulle, CA, Lahey, BB, Rathouz, PJ (2012). Operating characteristics of alternative statistical methods for detecting gene-by-measured environment interaction in the presence of gene-environment correlation in twin and sibling studies. Behavior Genetics 43, 71–84.CrossRefGoogle ScholarPubMed
Xian, H, Chantarujikapong, SI, Scherrer, JF, Eisen, SA, Lyons, MJ, Goldberg, J, Tsuang, M, True, WR (2000). Genetic and environmental influences on posttraumatic stress disorder, alcohol and drug dependence in twin pairs. Drug and Alcohol Dependence 61, 95–102.Google Scholar
Xie, P, Kranzler, HR, Poling, J, Stein, MB, Anton, RF, Brady, K, Weiss, RD, Farrer, L, Gelernter, J (2009). Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. Archives of General Psychiatry 66, 1201–1209.Google Scholar
Xie, P, Kranzler, HR, Poling, J, Stein, MB, Anton, RF, Farrer, LA, Gelernter, J (2010). Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology 35, 1684–1692.Google Scholar