Hostname: page-component-5d59c44645-lfgmx Total loading time: 0 Render date: 2024-03-01T02:32:48.774Z Has data issue: false hasContentIssue false

Posttraumatic stress disorder: from gene discovery to disease biology

Published online by Cambridge University Press:  15 February 2021

Renato Polimanti*
Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA Veterans Administration Connecticut Healthcare System, West Haven, CT, USA
Frank R. Wendt
Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA Veterans Administration Connecticut Healthcare System, West Haven, CT, USA
Author for correspondence: Renato Polimanti, E-mail:


Posttraumatic stress disorder (PTSD) is a complex mental disorder afflicting approximately 7% of the population. The diverse number of traumatic events and the wide array of symptom combinations leading to PTSD diagnosis contribute substantial heterogeneity to studies of the disorder. Genomic and complimentary-omic investigations have rapidly increased our understanding of the heritable risk for PTSD. In this review, we emphasize the contributions of genome-wide association, epigenome-wide association, transcriptomic, and neuroimaging studies to our understanding of PTSD etiology. We also discuss the shared risk between PTSD and other complex traits derived from studies of causal inference, co-expression, and brain morphological similarities. The investigations completed so far converge on stark contrasts in PTSD risk between sexes, partially attributed to sex-specific prevalence of traumatic experiences with high conditional risk of PTSD. To further understand PTSD biology, future studies should focus on detecting risk for PTSD while accounting for substantial cohort-level heterogeneity (e.g. civilian v. combat-exposed PTSD cases or PTSD risk among cases exposed to specific traumas), expanding ancestral diversity among study cohorts, and remaining cognizant of how these data influence social stigma associated with certain traumatic events among underrepresented minorities and/or high-risk populations.

Invited Review
Copyright © The Author(s), 2021. Published by Cambridge University Press

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.)


Afifi, T. O., Asmundson, G. J., Taylor, S., & Jang, K. L. (2010). The role of genes and environment on trauma exposure and posttraumatic stress disorder symptoms: A review of twin studies. Clinical Psychology Review, 30(1), 101112. doi:10.1016/j.cpr.2009.10.002.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013). Trauma- and stressor-related disorders diagnostic and statistical manual of mental disorders (Fifth ed.). American Psychiatric Association Publishing.Google Scholar
Atkinson, E. G., Maihofer, A. X., Kanai, M., Martin, A. R., Karczewski, K. J., Santoro, M. L., … Neale, B. M. (2020). “Tractor”: A framework allowing for improved inclusion of admixed individuals in large-scale association studies. bioRxiv, 2020.2005.2017.100727. doi: 10.1101/2020.05.17.100727.CrossRefGoogle Scholar
Ball, T. M., & Stein, M. B. (2012). Classification of Posttraumatic Stress Disorder. In Beck, J. G., & Sloan, D. M. (Eds.), The Oxford handbook of traumatic stress disorders (1st ed.). Oxford, England: Oxford Handbooks Online.Google Scholar
Benjet, C., Bromet, E., Karam, E. G., Kessler, R. C., McLaughlin, K. A., Ruscio, A. M., … Koenen, K. C. (2016). The epidemiology of traumatic event exposure worldwide: Results from the World Mental Health Survey Consortium. Psychological Medicine, 46(2), 327343. doi:10.1017/S0033291715001981.CrossRefGoogle ScholarPubMed
Bhatt, S., Hillmer, A. T., Girgenti, M. J., Rusowicz, A., Kapinos, M., Nabulsi, N., … Cosgrove, K. P. (2020). PTSD Is associated with neuroimmune suppression: Evidence from PET imaging and postmortem transcriptomic studies. Nature Communications, 11(1), 2360. doi:10.1038/s41467-020-15930-5.CrossRefGoogle ScholarPubMed
Border, R., Johnson, E. C., Evans, L. M., Smolen, A., Berley, N., Sullivan, P. F., & Keller, M. C. (2019). No support for historical candidate gene or candidate gene-by-interaction hypotheses for Major depression across multiple large samples. American Journal of Psychiatry, 176(5), 376387. doi:10.1176/appi.ajp.2018.18070881.CrossRefGoogle ScholarPubMed
Boscarino, J. A. (2004). Posttraumatic stress disorder and physical illness: Results from clinical and epidemiologic studies. Annals of the New York Academy of Sciences, 1032, 141153. doi:10.1196/annals.1314.011.CrossRefGoogle ScholarPubMed
Breen, M. S., Tylee, D. S., Maihofer, A. X., Neylan, T. C., Mehta, D., Binder, E. B., … Glatt, S. J. (2018). PTSD Blood transcriptome mega-analysis: Shared inflammatory pathways across biological Sex and modes of trauma. Neuropsychopharmacology, 43(3), 469481. doi:10.1038/npp.2017.220.CrossRefGoogle ScholarPubMed
Bulik-Sullivan, B., Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P. R., … Neale, B. M. (2015). An atlas of genetic correlations across human diseases and traits. Nature Genetics, 47(11), 12361241. doi:10.1038/ng.3406.CrossRefGoogle ScholarPubMed
Burns, J. G., Svetec, N., Rowe, L., Mery, F., Dolan, M. J., Boyce, W. T., & Sokolowski, M. B. (2012). Gene-environment interplay in Drosophila melanogaster: Chronic food deprivation in early life affects adult exploratory and fitness traits. Proceedings of the National Academy of Sciences of the United States of America, 109(Suppl 2), 1723917244. doi:10.1073/pnas.1121265109.CrossRefGoogle ScholarPubMed
Carvalho, C. M., Wendt, F. R., Stein, D. J., Stein, M. B., Gelernter, J., Belangero, S. I., & Polimanti, R. (2020). Investigating causality between blood metabolites and emotional and behavioral responses to traumatic stress: A mendelian randomization study. Molecular Neurobiology, 57(3), 15421552. doi: 10.1007/s12035-019-01823-2.CrossRefGoogle ScholarPubMed
Chakraborty, N., Meyerhoff, J., Jett, M., & Hammamieh, R. (2017). Genome to phenome: A systems biology approach to PTSD using an animal model. Methods in Molecular Biology, 1598, 117154. doi:10.1007/978-1-4939-6952-4_6.CrossRefGoogle ScholarPubMed
Chivers-Wilson, K. A. (2006). Sexual assault and posttraumatic stress disorder: A review of the biological, psychological and sociological factors and treatments. McGill Journal of Medicine, 9(2), 111118.Google ScholarPubMed
Coleman, J. R. I., Peyrot, W. J., Purves, K. L., Davis, K. A. S., Rayner, C., Choi, S. W., … Breen, G. (2020). Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK biobank. Molecular Psychiatry, 25(7), 14301446. doi:10.1038/s41380-019-0546-6.CrossRefGoogle ScholarPubMed
Comings, D. E., Muhleman, D., & Gysin, R. (1996). Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: A study and replication. Biological Psychiatry, 40(5), 368372. doi:10.1016/0006-3223(95)00519-6.CrossRefGoogle ScholarPubMed
Cox, R. C., Taylor, S., Strachan, E., & Olatunji, B. O. (2020). Insomnia and posttraumatic stress symptoms: Evidence of shared etiology. Psychiatry Research Search, 286, 112548. doi:10.1016/j.psychres.2019.112548.CrossRefGoogle ScholarPubMed
Dalvie, S., Maihofer, A. X., Coleman, J. R. I., Bradley, B., Breen, G., Brick, L. A., … Nievergelt, C. M. (2020). Genomic influences on self-reported childhood maltreatment. Translational Psychiatry, 10(1), 38. doi:10.1038/s41398-020-0706-0.CrossRefGoogle ScholarPubMed
Duncan, L. E., Cooper, B. N., & Shen, H. (2018). Robust findings from 25 years of PTSD genetics research. Current Psychiatry Reports, 20(12), 115. doi:10.1007/s11920-018-0980-1.CrossRefGoogle ScholarPubMed
Duncan, L. E., Ratanatharathorn, A., Aiello, A. E., Almli, L. M., Amstadter, A. B., Ashley-Koc-h, A. E., … Koenen, K. C. (2018). Largest GWAS of PTSD (N = 20 070) yields genetic overlap with schizophrenia and sex differences in heritability. Molecular Psychiatry, 23(3), 666673. doi:10.1038/mp.2017.77.CrossRefGoogle ScholarPubMed
Dunn, E. C., Nishimi, K., Powers, A., & Bradley, B. (2017). Is developmental timing of trauma exposure associated with depressive and post-traumatic stress disorder symptoms in adulthood? Journal of Psychiatric Research, 84, 119127. doi:10.1016/j.jpsychires.2016.09.004.CrossRefGoogle ScholarPubMed
Frueh, B. C., Elhai, J. D., & Acierno, R. (2010). The future of posttraumatic stress disorder in the DSM. Psychological Injury and Law, 3(4), 260270. doi:10.1007/s12207-010-9088-6.CrossRefGoogle Scholar
Gelernter, J., Sun, N., Polimanti, R., Pietrzak, R., Levey, D. F., Bryois, J., … Million Veteran, P. (2019). Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165000 US veterans. Nature Neuroscience, 22(9), 13941401. doi:10.1038/s41593-019-0447-7.CrossRefGoogle ScholarPubMed
Girgenti, M. J., Wang, J., Ji, D., Cruz, D. A., Traumatic Stress Brain Research, G., Stein, M. B., … Duman, R. S. (2021). Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience, 24(1), 2433. doi:10.1038/s41593-020-00748-7.CrossRefGoogle ScholarPubMed
Grotzinger, A. D., Rhemtulla, M., de Vlaming, R., Ritchie, S. J., Mallard, T. T., Hill, W. D., … Tucker-Drob, E. M. (2019). Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits. Nature Human Behaviour, 3(5), 513525. doi:10.1038/s41562-019-0566-x.CrossRefGoogle ScholarPubMed
Guffanti, G., Galea, S., Yan, L., Roberts, A. L., Solovieff, N., Aiello, A. E., … Koenen, K. C. (2013). Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women. Psychoneuroendocrinology, 38(12), 30293038. doi:10.1016/j.psyneuen.2013.08.014.CrossRefGoogle ScholarPubMed
Gupta, M. A. (2013). Review of somatic symptoms in post-traumatic stress disorder. International Review of Psychiatry, 25(1), 8699. doi:10.3109/09540261.2012.736367.CrossRefGoogle ScholarPubMed
Hammamieh, R., Chakraborty, N., Gautam, A., Muhie, S., Yang, R., Donohue, D., … Jett, M. (2017). Whole-genome DNA methylation status associated with clinical PTSD measures of OIF/OEF veterans. Translational Psychiatry, 7(7), e1169. doi:10.1038/tp.2017.129.CrossRefGoogle ScholarPubMed
Hasin, Y., Seldin, M., & Lusis, A. (2017). Multi-omics approaches to disease. Genome Biolology, 18(1), 83. doi:10.1186/s13059-017-1215-1.CrossRefGoogle ScholarPubMed
Heck, A., Milnik, A., Vukojevic, V., Petrovska, J., Egli, T., Singer, J., … Papassotiropoulos, A. (2017). Exome sequencing of healthy phenotypic extremes links TROVE2 to emotional memory and PTSD. Nature Human Behaviour, 1(4), 0081. doi:10.1038/s41562-017-0081.CrossRefGoogle Scholar
Holland, D., Frei, O., Desikan, R., Fan, C. C., Shadrin, A. A., Smeland, O. B., … Dale, A. M. (2020). Beyond SNP heritability: Polygenicity and discoverability of phenotypes estimated with a univariate Gaussian mixture model. PLOS Genetics, 16(5), e1008612. doi:10.1371/journal.pgen.1008612.CrossRefGoogle ScholarPubMed
Huckins, L. M., Chatzinakos, C., Breen, M. S., Hartmann, J., Klengel, T., da Silva Almeida, A. C., … Daskalakis, N. P. (2020). Analysis of genetically regulated gene expression identifies a prefrontal PTSD gene, SNRNP35, specific to military cohorts. Cell Reports, 31(9), 107716. doi:10.1016/j.celrep.2020.107716.CrossRefGoogle ScholarPubMed
Jin, M. J., Jeon, H., Hyun, M. H., & Lee, S. H. (2019). Influence of childhood trauma and brain-derived neurotrophic factor Val66Met polymorphism on posttraumatic stress symptoms and cortical thickness. Scientific Reports, 9(1), 6028. doi:10.1038/s41598-019-42563-6.CrossRefGoogle ScholarPubMed
Kennedy, A. C., & Prock, K. A. (2018). “I still feel like I am not normal”: A review of the role of stigma and stigmatization Among female survivors of child sexual abuse, sexual assault, and intimate partner violence. Trauma, Violence & Abuse, 19(5), 512527. doi:10.1177/1524838016673601.CrossRefGoogle ScholarPubMed
Kessler, R. C., Aguilar-Gaxiola, S., Alonso, J., Benjet, C., Bromet, E. J., Cardoso, G., … Koenen, K. C. (2017). Trauma and PTSD in the WHO World Mental Health Surveys. European Journal of Psychotraumatology, 8(sup5), 1353383. doi:10.1080/20008198.2017.1353383.CrossRefGoogle ScholarPubMed
Kilpatrick, D. G., Koenen, K. C., Ruggiero, K. J., Acierno, R., Galea, S., Resnick, H. S., … 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(11), 16931699. doi:10.1176/appi.ajp.2007.06122007.CrossRefGoogle ScholarPubMed
Koenen, K. C., Ratanatharathorn, A., Ng, L., McLaughlin, K. A., Bromet, E. J., Stein, D. J., … Kessler, R. C. (2017a). Posttraumatic stress disorder in the World Mental Health Surveys. Psychological Medicine, 47(13), 22602274. doi:10.1017/S0033291717000708.CrossRefGoogle Scholar
Koenen, K. C., Sumner, J. A., Gilsanz, P., Glymour, M. M., Ratanatharathorn, A., Rimm, E. B., … Kubzansky, L. D. (2017b). Post-traumatic stress disorder and cardiometabolic disease: Improving causal inference to inform practice. Psychological Medicine, 47(2), 209225. doi:10.1017/S0033291716002294.CrossRefGoogle Scholar
Kolassa, I. T., Kolassa, S., Ertl, V., Papassotiropoulos, A., & De Quervain, D. J. (2010). The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. Biological Psychiatry, 67(4), 304308. doi:10.1016/j.biopsych.2009.10.009.CrossRefGoogle ScholarPubMed
Kuan, P. F., Waszczuk, M. A., Kotov, R., Clouston, S., Yang, X., Singh, P. K., … Luft, B. J. (2017a). Gene expression associated with PTSD in World Trade Center responders: An RNA sequencing study. Translational Psychiatry, 7(12), 1297. doi:10.1038/s41398-017-0050-1.CrossRefGoogle Scholar
Kuan, P. F., Waszczuk, M. A., Kotov, R., Marsit, C. J., Guffanti, G., Gonzalez, A., … Luft, B. J. (2017b). An epigenome-wide DNA methylation study of PTSD and depression in World Trade Center responders. Translational Psychiatry, 7(6), e1158. doi:10.1038/tp.2017.130.CrossRefGoogle Scholar
Kuan, P. F., Yang, X., Clouston, S., Ren, X., Kotov, R., Waszczuk, M., … Luft, B. J. (2019). Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders. Translational Psychiatry, 9(1), 1. doi:10.1038/s41398-018-0355-8.CrossRefGoogle ScholarPubMed
Lind, M. J., Brick, L. A., Gehrman, P. R., Duncan, L. E., Gelaye, B., & Maihofer, A. X., … Psychiatric Genomics Consortium Posttraumatic Stress, D. (2020). Molecular genetic overlap between posttraumatic stress disorder and sleep phenotypes. Sleep, 43(4), zsz257. doi:10.1093/sleep/zsz257.CrossRefGoogle ScholarPubMed
Logue, M. W., Baldwin, C., Guffanti, G., Melista, E., Wolf, E. J., Reardon, A. F., … Miller, M. W. (2013). A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus. Molecular Psychiatry, 18(8), 937942. doi:10.1038/mp.2012.113.CrossRefGoogle ScholarPubMed
Logue, M. W., Miller, M. W., Wolf, E. J., Huber, B. R., Morrison, F. G., Zhou, Z., … Traumatic Stress Brain Study, G. (2020). An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci. Clininical Epigenetics, 12(1), 46. doi:10.1186/s13148-020-0820-0.CrossRefGoogle ScholarPubMed
Lohr, J. B., Palmer, B. W., Eidt, C. A., Aailaboyina, S., Mausbach, B. T., Wolkowitz, O. M., … Jeste, D. V. (2015). Is post-traumatic stress disorder associated with premature senescence? A review of the literature. American Journal of Geriatric Psychiatry, 23(7), 709725. doi:10.1016/j.jagp.2015.04.001.CrossRefGoogle ScholarPubMed
Lutz, M. W., Luo, S., Williamson, D. E., & Chiba-Falek, O. (2020). Shared genetic etiology underlying late-onset alzheimer's disease and posttraumatic stress syndrome. Alzheimer's & Dementia, 16(9), 12801292. doi:10.1002/alz.12128.CrossRefGoogle ScholarPubMed
McCall, C. A., Turkheimer, E., Tsang, S., Avery, A., Duncan, G. E., & Watson, N. F. (2019). Sleep duration and post-traumatic stress disorder symptoms: A twin study. Sleep, 42(12), zsz179. doi:10.1093/sleep/zsz179.CrossRefGoogle ScholarPubMed
Mehta, D., Klengel, T., Conneely, K. N., Smith, A. K., Altmann, A., Pace, T. W., … Binder, E. B. (2013). Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America, 110(20), 83028307. doi: 10.1073/pnas.1217750110.CrossRefGoogle ScholarPubMed
Morey, R. A., Davis, S. L., Garrett, M. E., Haswell, C. C., Mid-Atlantic, M. W., Marx, C. E., … Ashley-Koch, A. E. (2017). Genome-wide association study of subcortical brain volume in PTSD cases and trauma-exposed controls. Translational Psychiatry, 7(11), 1265. doi:10.1038/s41398-017-0021-6.CrossRefGoogle ScholarPubMed
Muniz Carvalho, C., Wendt, F. R., Maihofer, A. X., Stein, D. J., Stein, M. B., Sumner, J. A., … Polimanti, R. (2020). Dissecting the genetic association of C-reactive protein with PTSD, traumatic events, and social support. Neuropsychopharmacology. doi:10.1038/s41386-020-0655-6.Google ScholarPubMed
Ng, L. C., Stevenson, A., Kalapurakkel, S. S., Hanlon, C., Seedat, S., Harerimana, B., … Koenen, K. C. (2020). National and regional prevalence of posttraumatic stress disorder in sub-Saharan Africa: A systematic review and meta-analysis. PLoS Medicine, 17(5), e1003090. doi:10.1371/journal.pmed.1003090.CrossRefGoogle ScholarPubMed
Nievergelt, C. M., Ashley-Koch, A. E., Dalvie, S., Hauser, M. A., Morey, R. A., Smith, A. K., & Uddin, M. (2018). Genomic approaches to posttraumatic stress disorder: The psychiatric genomic consortium initiative. Biological Psychiatry, 83(10), 831839. doi:10.1016/j.biopsych.2018.01.020.CrossRefGoogle ScholarPubMed
Nievergelt, C. M., Maihofer, A. X., Klengel, T., Atkinson, E. G., Chen, C. Y., Choi, K. W., … Koenen, K. C. (2019). International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nature Communications, 10(1), 4558. doi:10.1038/s41467-019-12576-w.CrossRefGoogle ScholarPubMed
Nievergelt, C. M., Maihofer, A. X., Mustapic, M., Yurgil, K. A., Schork, N. J., Miller, M. W., … Baker, D. G. (2015). Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene. Psychoneuroendocrinology, 51, 459471. doi:10.1016/j.psyneuen.2014.10.017.CrossRefGoogle ScholarPubMed
Olbert, C. M., Gala, G. J., & Tupler, L. A. (2014). Quantifying heterogeneity attributable to polythetic diagnostic criteria: Theoretical framework and empirical application. Journal of Abnormal Psychology, 123(2), 452462. doi:10.1037/a0036068.CrossRefGoogle ScholarPubMed
Palmer, C., & Pe'er, I. (2017). Statistical correction of the Winner's Curse explains replication variability in quantitative trait genome-wide association studies. PLoS Genetics, 13(7), e1006916. doi:10.1371/journal.pgen.1006916.CrossRefGoogle ScholarPubMed
Papa, A., Neria, Y., & Litz, B. (2008). Traumatic bereavement in war veterans. Psychiatric Annals, 38(10), 686691. doi:10.3928/00485713-20081001-07.CrossRefGoogle Scholar
Polimanti, R., Amstadter, A. B., Stein, M. B., Almli, L. M., Baker, D. G., & Bierut, L. J., … Psychiatric Genomics Consortium Posttraumatic Stress Disorder, W. (2017). A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder. Genome Medicine, 9(1), 99. doi:10.1186/s13073-017-0491-4.CrossRefGoogle ScholarPubMed
Polimanti, R., Kaufman, J., Zhao, H., Kranzler, H. R., Ursano, R. J., Kessler, R. C., … Gelernter, J. (2018a). Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers. Acta Psychiatrica Scandinavica, 137(2), 148156. doi:10.1111/acps.12843.CrossRefGoogle Scholar
Polimanti, R., Kaufman, J., Zhao, H., Kranzler, H. R., Ursano, R. J., Kessler, R. C., … Stein, M. B. (2018b). A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus. Molecular Psychiatry, 23(1), 154160. doi:10.1038/mp.2017.24.CrossRefGoogle Scholar
Polimanti, R., Ratanatharathorn, A., Maihofer, A. X., Choi, K. W., Stein, M. B., Morey, R. A., … Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working, G. (2019). Association of economic Status and educational attainment with posttraumatic stress disorder: A mendelian randomization study. JAMA Network Open, 2(5), e193447. doi:10.1001/jamanetworkopen.2019.3447.CrossRefGoogle ScholarPubMed
Ratanatharathorn, A., Boks, M. P., Maihofer, A. X., Aiello, A. E., Amstadter, A. B., Ashley-Koch, A. E., … Smith, A. K. (2017). Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 174(6), 619630. doi:10.1002/ajmg.b.32568.CrossRefGoogle ScholarPubMed
Ressler, K. J., Mercer, K. B., Bradley, B., Jovanovic, T., Mahan, A., Kerley, K., … May, V. (2011). Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature, 470(7335), 492497. doi:10.1038/nature09856.CrossRefGoogle ScholarPubMed
Rivollier, F., Peyre, H., Hoertel, N., Blanco, C., Limosin, F., & Delorme, R. (2015). Sex differences in DSM-IV posttraumatic stress disorder symptoms expression using item response theory: A population-based study. Journal of Affective Disorders, 187, 211217. doi:10.1016/j.jad.2015.07.047.CrossRefGoogle ScholarPubMed
Roberts, A. L., Huang, T., Koenen, K. C., Kim, Y., Kubzansky, L. D., & Tworoger, S. S. (2019). Posttraumatic stress disorder Is associated with increased risk of ovarian cancer: A prospective and retrospective longitudinal cohort study. Cancer Research, 79(19), 51135120. doi:10.1158/0008-5472.CAN-19-1222.CrossRefGoogle ScholarPubMed
Roberts, N. P., Roberts, P. A., Jones, N., & Bisson, J. I. (2015). Psychological interventions for post-traumatic stress disorder and comorbid substance use disorder: A systematic review and meta-analysis. Clinical Psychology Review, 38, 2538. doi:10.1016/j.cpr.2015.02.007.CrossRefGoogle ScholarPubMed
Sack, W. H., Clarke, G. N., & Seeley, J. (1995). Posttraumatic stress disorder across two generations of Cambodian refugees. Journal of the American Academy of Child and Adolescent Psychiatry, 34(9), 11601166. doi:10.1097/00004583-199509000-00013.CrossRefGoogle ScholarPubMed
Salminen, L. E., Sämann, P. G., Zheng, Y., Dennis, E. L., Clarke-Rubright, E. K., Jahanshad, N., … Logue, M. W. (2019). Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD working group. bioRxiv, doi: 739094. doi: 10.1101/739094.CrossRefGoogle Scholar
Sareen, J. (2020). Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis. Retrieved September 1, 2020, from Scholar
Sartor, C. E., Grant, J. D., Lynskey, M. T., McCutcheon, V. V., Waldron, M., Statham, D. J., … Nelson, E. C. (2012). Common heritable contributions to low-risk trauma, high-risk trauma, posttraumatic stress disorder, and major depression. Archives of General Psychiatry, 69(3), 293299. doi:10.1001/archgenpsychiatry.2011.1385.CrossRefGoogle ScholarPubMed
Savas, L. S., White, D. L., Wieman, M., Daci, K., Fitzgerald, S., Laday Smith, S., … El-Serag, H. B. (2009). Irritable bowel syndrome and dyspepsia among women veterans: Prevalence and association with psychological distress. Alimentary Pharmacology & Therapeutics, 29(1), 115125. doi:10.1111/j.1365-2036.2008.03847.x.CrossRefGoogle ScholarPubMed
Schijven, D., Geuze, E., Vinkers, C. H., Pulit, S. L., Schur, R. R., Malgaz, M., … Luykx, J. J. (2019). Multivariate genome-wide analysis of stress-related quantitative phenotypes. European Neuropsychopharmacology, 29(12), 13541364. doi:10.1016/j.euroneuro.2019.09.012.CrossRefGoogle ScholarPubMed
Segman, R. H., Cooper-Kazaz, R., Macciardi, F., Goltser, T., Halfon, Y., Dobroborski, T., & Shalev, A. Y. (2002). Association between the dopamine transporter gene and posttraumatic stress disorder. Molecular Psychiatry, 7(8), 903907. doi:10.1038/ ScholarPubMed
Shand, L. K., Cowlishaw, S., Brooker, J. E., Burney, S., & Ricciardelli, L. A. (2015). Correlates of post-traumatic stress symptoms and growth in cancer patients: A systematic review and meta-analysis. Psycho-oncology, 24(6), 624634. doi:10.1002/pon.3719.CrossRefGoogle ScholarPubMed
Sheerin, C. M., Lind, M. J., Bountress, K. E., Marraccini, M. E., Amstadter, A. B., Bacanu, S. A., … Nugent, N. R. (2020). Meta-analysis of associations between hypothalamic-pituitary-adrenal axis genes and risk of posttraumatic stress disorder. Journal of Traumatic Stress, 33(5), 688698. doi:10.1002/jts.22484.CrossRefGoogle ScholarPubMed
Sirugo, G., Williams, S. M., & Tishkoff, S. A. (2019). The missing diversity in human genetic studies. Cell, 177(1), 2631. doi:10.1016/j.cell.2019.02.048.CrossRefGoogle ScholarPubMed
Skelton, K., Ressler, K. J., Norrholm, S. D., Jovanovic, T., & Bradley-Davino, B. (2012). PTSD And gene variants: New pathways and new thinking. Neuropharmacology, 62(2), 628637. doi:10.1016/j.neuropharm.2011.02.013.CrossRefGoogle ScholarPubMed
Smith, G. D., & Ebrahim, S. (2003). ‘Mendelian randomization’: Can genetic epidemiology contribute to understanding environmental determinants of disease? International Journal of Epidemiology, 32(1), 122. doi:10.1093/ije/dyg070.CrossRefGoogle ScholarPubMed
Smith, A. K., Ratanatharathorn, A., Maihofer, A. X., Naviaux, R. K., Aiello, A. E., Amstadter, A. B., … Nievergelt, C. M. (2020). Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies novel methylation loci. Nature Communications, 11(1), 5965. doi:10.1038/s41467-020-19615-x.CrossRefGoogle Scholar
Smoller, J. W. (2016). The genetics of stress-related disorders: PTSD, depression, and anxiety disorders. Neuropsychopharmacology, 41(1), 297319. doi:10.1038/npp.2015.266.CrossRefGoogle ScholarPubMed
Snijders, C., Maihofer, A. X., Ratanatharathorn, A., Baker, D. G., Boks, M. P., Geuze, E., … Nievergelt, C. M. (2020). Longitudinal epigenome-wide association studies of three male military cohorts reveal multiple CpG sites associated with post-traumatic stress disorder. Clininical Epigenetics, 12(1), 11. doi:10.1186/s13148-019-0798-7.CrossRefGoogle ScholarPubMed
Stein, M. B., Chen, C. Y., Ursano, R. J., Cai, T., Gelernter, J., Heeringa, S. G., … Resilience in Servicemembers, C. (2016). Genome-wide association studies of posttraumatic stress disorder in 2 cohorts of US army soldiers. JAMA Psychiatry, 73(7), 695704. doi:10.1001/jamapsychiatry.2016.0350.CrossRefGoogle ScholarPubMed
Stein, M. B., Jang, K. L., Taylor, S., Vernon, P. A., & Livesley, W. J. (2002). Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: A twin study. American Journal of Psychiatry, 159(10), 16751681. doi:10.1176/appi.ajp.159.10.1675.CrossRefGoogle ScholarPubMed
Stein, M. B., Levey, D. F., Cheng, Z., Wendt, F. R., Harrington, K., Cho, K., … Gelernter, J. (2019). Genomic characterization of posttraumatic stress disorder in a large US military veteran sample. bioRxiv, doi: 764001. doi: 10.1101/764001.CrossRefGoogle Scholar
Sul, J. H., Martin, L. S., & Eskin, E. (2018). Population structure in genetic studies: Confounding factors and mixed models. PLoS Genetics, 14(12), e1007309. doi:10.1371/journal.pgen.1007309.CrossRefGoogle ScholarPubMed
Sullivan, P. F., Agrawal, A., Bulik, C. M., Andreassen, O. A., Borglum, A. D., Breen, G., … Psychiatric Genomics, C. (2018). Psychiatric genomics: An update and an agenda. American Journal of Psychiatry, 175(1), 1527. doi:10.1176/appi.ajp.2017.17030283.CrossRefGoogle Scholar
Tamman, A. J. F., Wendt, F. R., Pathak, G. A., Krystal, J. H., Montalvo-Ortiz, J. L., Southwick, S. M., … Pietrzak, R. H. (2020). Attachment style moderates polygenic risk for posttraumatic stress in United States Military Veterans: Results from the national health and resilience in veterans study. Biological Psychiatry. doi:10.1016/j.biopsych.2020.09.018.Google ScholarPubMed
Thakur, G. S., Daigle, B. J. Jr., Dean, K. R., Zhang, Y., Rodriguez-Fernandez, M., Hammamieh, R., … Doyle, F. J. 3rd. (2015). Systems biology approach to understanding post-traumatic stress disorder. Molecular BioSystems, 11(4), 980993. doi: 10.1039/c4mb00404c.CrossRefGoogle ScholarPubMed
Uddin, M., Ratanatharathorn, A., Armstrong, D., Kuan, P. F., Aiello, A. E., Bromet, E. J., … Smith, A. (2018). Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder. Epigenomics, 10(12), 15851601. doi:10.2217/epi-2018-0049.CrossRefGoogle ScholarPubMed
van der Merwe, C., Jahanshad, N., Cheung, J. W., Mufford, M., Groenewold, N. A., Koen, N., … Stein, D. J. (2019). Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry. Journal of Affective Disorders, 245, 885896. doi:10.1016/j.jad.2018.11.082.CrossRefGoogle ScholarPubMed
van Rooij, S. J., Stevens, J. S., Ely, T. D., Fani, N., Smith, A. K., Kerley, K. A., … Jovanovic, T. (2016). Childhood trauma and COMT genotype interact to increase hippocampal activation in resilient individuals. Frontiers in Psychiatry, 7, 156. doi:10.3389/fpsyt.2016.00156.CrossRefGoogle ScholarPubMed
Victor, S. E., & Klonsky, E. D. (2014). Correlates of suicide attempts among self-injurers: A meta-analysis. Clinical Psychology Review, 34(4), 282297. doi:10.1016/j.cpr.2014.03.005.CrossRefGoogle ScholarPubMed
Wainschtein, P., Jain, D. P., Yengo, L., Zheng, Z., Cupples, L. A., Shadyab, A. H., … Visscher, P. M. (2019). Recovery of trait heritability from whole genome sequence data. bioRxiv, doi: 588020. doi: 10.1101/588020.CrossRefGoogle Scholar
Wang, Q., Shelton, R. C., & Dwivedi, Y. (2018). Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis. Journal of Affective Disorders, 225, 422428. doi:10.1016/j.jad.2017.08.066.CrossRefGoogle ScholarPubMed
Wendt, F. R., Pathak, G. A., Levey, D. F., Nunez, Y. Z., Overstreet, C., Tyrrell, C., … Polimanti, R. (2020a). Trauma and posttraumatic stress interact with sex-specific risk loci for suicidality and converge on brain extracellular matrix biology and synaptic plasticity. medRxiv, doi: 2020.2005.2018.20105734. doi: 10.1101/2020.05.18.20105734.CrossRefGoogle Scholar
Wendt, F. R., Pathak, G. A., Overstreet, C., Tylee, D. S., Gelernter, J., Atkinson, E. G., & Polimanti, R. (2020b). Characterizing the effect of background selection on the polygenicity of brain-related traits. Genomics, 113(1 Pt 1), 111119. doi:10.1016/j.ygeno.2020.11.032.CrossRefGoogle Scholar
Wild, J., Smith, K. V., Thompson, E., Bear, F., Lommen, M. J., & Ehlers, A. (2016). A prospective study of pre-trauma risk factors for post-traumatic stress disorder and depression. Psychological Medicine, 46(12), 25712582. doi:10.1017/S0033291716000532.CrossRefGoogle ScholarPubMed
Wolf, E. J., Logue, M. W., Morrison, F. G., Wilcox, E. S., Stone, A., Schichman, S. A., … Miller, M. W. (2019). Posttraumatic psychopathology and the pace of the epigenetic clock: A longitudinal investigation. Psychological Medicine, 49(5), 791800. doi:10.1017/S0033291718001411.CrossRefGoogle ScholarPubMed
Wolf, E. J., Logue, M. W., Stoop, T. B., Schichman, S. A., Stone, A., Sadeh, N., … Miller, M. W. (2018a). Accelerated DNA methylation age: Associations with posttraumatic stress disorder and mortality. Psychosomatic Medicine, 80(1), 4248. doi:10.1097/PSY.0000000000000506.CrossRefGoogle Scholar
Wolf, E. J., Maniates, H., Nugent, N., Maihofer, A. X., Armstrong, D., Ratanatharathorn, A., … Logue, M. W. (2018b). Traumatic stress and accelerated DNA methylation age: A meta-analysis. Psychoneuroendocrinology, 92, 123134. doi:10.1016/j.psyneuen.2017.12.007.CrossRefGoogle Scholar
Wolf, E. J., Miller, M. W., Sullivan, D. R., Amstadter, A. B., Mitchell, K. S., Goldberg, J., & Magruder, K. M. (2018c). A classical twin study of PTSD symptoms and resilience: Evidence for a single spectrum of vulnerability to traumatic stress. Depression and Anxiety, 35(2), 132139. doi:10.1002/da.22712.CrossRefGoogle Scholar
Wu, G., Feder, A., Cohen, H., Kim, J. J., Calderon, S., Charney, D. S., & Mathe, A. A. (2013). Understanding resilience. Frontiers in Behavioral Neuroscience, 7, 10. doi:10.3389/fnbeh.2013.00010.CrossRefGoogle ScholarPubMed
Xie, P., Kranzler, H. R., Yang, C., Zhao, H., Farrer, L. A., & Gelernter, J. (2013). Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder. Biological Psychiatry, 74(9), 656663. doi: 10.1016/j.biopsych.2013.04.013.CrossRefGoogle ScholarPubMed
Yang, B. Z., Zhang, H., Ge, W., Weder, N., Douglas-Palumberi, H., Perepletchikova, F., … Kaufman, J. (2013). Child abuse and epigenetic mechanisms of disease risk. American Journal of Preventive Medicine, 44(2), 101107. doi:10.1016/j.amepre.2012.10.012.CrossRefGoogle ScholarPubMed
Yehuda, R., Halligan, S. L., & Bierer, L. M. (2001). Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring. Journal of Psychiatric Research, 35(5), 261270. doi:10.1016/s0022-3956(01)00032-2.CrossRefGoogle ScholarPubMed
Yeshurun, S., & Hannan, A. J. (2019). Transgenerational epigenetic influences of paternal environmental exposures on brain function and predisposition to psychiatric disorders. Molecular Psychiatry, 24(4), 536548. doi:10.1038/s41380-018-0039-z.CrossRefGoogle ScholarPubMed
Zang, Y., Gallagher, T., McLean, C. P., Tannahill, H. S., Yarvis, J. S., Foa, E. B., & Consortium, S. S. (2017). The impact of social support, unit cohesion, and trait resilience on PTSD in treatment-seeking military personnel with PTSD: The role of posttraumatic cognitions. Journal of Psychiatric Research, 86, 1825. doi:10.1016/j.jpsychires.2016.11.005.CrossRefGoogle ScholarPubMed
Zannas, A. S., Provencal, N., & Binder, E. B. (2015). Epigenetics of posttraumatic stress disorder: Current evidence, challenges, and future directions. Biological Psychiatry, 78(5), 327335. doi:10.1016/j.biopsych.2015.04.003.CrossRefGoogle ScholarPubMed
Zhang, L., Hu, X. Z., Yu, T., Chen, Z., Dohl, J., Li, X., … Ursano, R. J. (2020). Genetic association of FKBP5 with PTSD in US service members deployed to Iraq and Afghanistan. Journal of Psychiatric Research, 122, 4853. doi:10.1016/j.jpsychires.2019.12.014.CrossRefGoogle ScholarPubMed
Zhang, H., Ozbay, F., Lappalainen, J., Kranzler, H. R., van Dyck, C. H., Charney, D. S., … Gelernter, J. (2006). Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer's disease, affective disorders, posttraumatic stress disorder, schizophrenia, and substance dependence. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 141B(4), 387393. doi:10.1002/ajmg.b.30332.CrossRefGoogle ScholarPubMed