Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-25T12:29:23.001Z Has data issue: false hasContentIssue false

Chapter 8 - How the Spitak Earthquake Contributed to our Understanding of the Genetics of PTSD and Associated Disorders

Published online by Cambridge University Press:  20 May 2022

By
Julia Bailey  and
Armen Goenjian
Edited by
Armen Goenjian ,
Alan Steinberg  and
Robert Pynoos
Armen Goenjian
Affiliation:
David Geffen School of Medicine; UCLA/Duke University National Center for Child Traumatic Stress
Alan Steinberg
Affiliation:
UCLA/Duke University National Center for Child Traumatic Stress
Robert Pynoos
Affiliation:
UCLA/Duke University National Center for Child Traumatic Stress
Get access

Summary

The Spitak earthquake offered a unique opportunity to conduct family studies of the genetics of post-traumatic stress disorder (PTSD) and related conditions, including depression and anxiety. The multigenerational families that participated in the Spitak Earthquake Genetic Study (SEGS) were recruited from the devastated city of Gumri. The participants (3 to 5 generations) were exposed to horrific earthquake-related traumatic experiences contemporaneously. After adjusting for sex, age, and multiple environmental risk factors, the heritability of vulnerability of PTSD (42%) was significant. Additionally, vulnerabilities for depression and anxiety were also significantly heritable. These three phenotypes were genetically correlated, indicating pleiotropy, i.e., they shared genes. Using complex co-variate analyses, we found an association of specific serotonergic genes (THP2 and THP1) and a dopaminergic gene (COMT) with PTSD and a serotonergic gene (5HTTLRP) with depression. These findings suggest that carriers of variants of these genes are at risk for PTSD and depression, respectively. Whole genome sequencing found another interesting gene, OR4C3, among those with PTSD. The gene codes for an olfactory receptor that shares a domain structure with many neurotransmitters. The chapter also discusses recent advances and challenges in genetic research.

Keywords

HeritabilitygeneticsPTSDdepressionanxietylinkagegenome-wide association studiespleiotropy
Type
Chapter
Information
Lessons Learned in Disaster Mental Health
The Earthquake in Armenia and Beyond
 , pp. 137 - 151
Publisher: Cambridge University Press
Print publication year: 2022

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

Almasy, L. A., Williams, J. T., Dyer, T. D., & Blangero, J. (1999). Quantitative trait locus detection using combined linkage/disequilibrium analysis. Genetic Epidemiology, 17 (Suppl. 1), S31–S36.CrossRefGoogle ScholarPubMed
Almli, L. M., Stevens, J. S., Smith, A. K., Kilaru, V., Meng, Q., Flory, J., Abu-Amara, D., … & Ressler, K. J. (2015). A genome-wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces. American Journal of Medical Genetics B Neuropsychiatric Genetics, 168B (5), 327–336.Google Scholar
Ashley-Koch, A. E., Garrett, M. E., Gibson, J., Liu, Y., Dennis, M. F., Kimbrel, N. A., … & Hauser, M. A. (2015). Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. Journal of Affective Disorder, 15 (184), 225–234.Google Scholar
Bailey, J. N., & Almasy, L. A. (1995). A brute force dichotomization approach to quantitative trait linkage analyses. Genetic Epidemiology, 12, 719–722.Google Scholar
Bailey, J. N., Goenjian, A. K., Noble, E. P. , Walling, D. P., Ritchie, T., & Goenjian, H. A. (2010). PTSD and dopaminergic genes, DRD2 and DAT, in multigenerational families exposed to the Spitak earthquake. Psychiatry Research, 178 (3), 507–510.CrossRefGoogle Scholar
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), 368–372.CrossRefGoogle ScholarPubMed
Daley, J. (2019). Gene therapy arrives. Nature, 576, S12–S13.CrossRefGoogle Scholar
Davidson, J., Swartz, M., Storck, M., Krishnan, R. R., & Hammett, E. (1985). A diagnostic and family study of posttraumatic stress disorder. American Journal of Psychiatry, 142 (1), 90–93.Google ScholarPubMed
Davidson, J., Smith, R., & Kudler, H. (1989). Familial psychiatric illness in chronic posttraumatic stress disorder. Comprehensive Psychiatry, 30 (4), 339–345.Google Scholar
Dierker, L. C., & Merikangas, K. R. (2001). Familial psychiatric illness and posttraumatic stress disorder: findings from a family study of substance abuse and anxiety disorders. Journal of Clinical Psychiatry, 62 (9): 715–720.Google Scholar
Dileo, J. F., Brewer, W. J., Hopwood, M., Anderson, V., Creamer, M. (2008). Olfactory identification dysfunction, aggression and impulsivity in war veterans with posttraumatic stress disorder. Psychological Medicine, 38, 523–531.Google Scholar
Duncan, L. E., Ratanatharathorn, A., Aiello, A. E., Almli, L. M., Amstadter, A. B., Ashley-Koch, 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), 666–673.Google Scholar
Garriock, H. A., Kraft, J. B., Shyn, S. I., Peters, E. J., Yokoyama, J. S., Jenkins, G. D., … & Hamilton, S. P. (2010). A genome-wide association study of citalopram response in major depressive disorder. Biological Psychiatry, 67 (2), 133–138.Google Scholar
Gelernter, J., Southwick, S., Goodson, S., Morgan, A., Nagy, L., Charney, D. S. (1999). No association between D2 dopamine receptor (DRD2) “A” system alleles, or DRD2 haplotypes, and posttraumatic stress disorder. Biological Psychiatry, 45, 620–625.CrossRefGoogle ScholarPubMed
Gelernter, J., Sun, N., Polimanti, R., Robert, P., Levey, D. F., Bryois, J., … & Stein, M. B. (2019). Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nature Neuroscience, 22 (9), 1394–1401.CrossRefGoogle Scholar
Goenjian, A., Najarian, M., Pynoos, R. S., Steinberg, A. M., Manoukian, G., Tavosian, A., & Fairbanks, L. (1994a). Posttraumatic stress disorder in adults and elderly after the 1988 earthquake in Armenia. American Journal of Psychiatry, 151, 895–901.Google Scholar
Goenjian, A., Najarian, L. M., Pynoos, R. S., Steinberg, A. M., Petrosian, P., Setrakyan, S., & Fairbanks, L. A. (1994b). Posttraumatic stress reactions after single and double trauma. Acta Psychiatrica Scandinavia, 90, 214–221.Google Scholar
Goenjian, A. K., Pynoos, R. S., Steinberg, A. M., Najarian, L. M., Asarnow, J. R., Karayan, I. … & Fairbanks, L. A. (1995). Psychiatric co-morbidity in children after the 1988 earthquake in Armenia. Journal of the American Academy of Child and Adolescent Psychiatry, 34, 1174–1184.Google Scholar
Goenjian, A. K., Karayan, I., Pynoos, R. S., Minassian, D., Najarian, L. M., Steinberg, A. M., & Fairbanks, L. A. (1997). Outcome of psychotherapy among early adolescents after trauma. American Journal of Psychiatry, 154(4), 536–542.Google ScholarPubMed
Goenjian, A. K, Najarian, L. M., Steinberg, A. M., Fairbanks, L. A., Tashjian, M., & Pynoos, R. S. (2000). A prospective study of post-traumatic stress, anxiety, and depressive reactions after earthquake and violence. American Journal of Psychiatry, 157, 911–916.CrossRefGoogle Scholar
Goenjian, A. K., Molina, L., Steinberg, A. M., Fairbanks, L. A., Alvarez, M. L., Goenjian, H. A., & Pynoos, R. S. (2001). Post-traumatic stress and depressive reactions among Nicaraguan adolescents after Hurricane Mitch. American Journal of Psychiatry, 158, 788–794.CrossRefGoogle ScholarPubMed
Goenjian, A. K., Noble, E. P., Walling, D. P., Goenjian, H. A., Karayan, I. S., Ritchie, T., & Bailey, J. N. (2008). Heritabilities of symptoms of posttraumatic stress disorder, anxiety and depression in earthquake-exposed Armenian families. Psychiatric Genetics, 18, 261–266.Google Scholar
Goenjian, A. K., Bailey, J. N., Walling, D. P., Steinberg, A. S., Schmidt, D., Dandekar, U., & Noble, E. P. (2012) Association of TPH1, TPH2, and 5HTTLPR with PTSD and depression. Journal of Affective Disorders, 140, 244–252.Google Scholar
Goenjian, A. K., Noble, E. P., Steinberg, A. M., Walling, D. P., Stepanyan, S. T., Dandekar, S., & Bailey, J. N. (2015). Association of COMT and TPH-2 genes with DSM-5-based PTSD symptoms. Journal of Affective Disorders, 172, 472–478.CrossRefGoogle ScholarPubMed
Goenjian, A. K., Steinberg, A., Walling, D., Bishop, S., Karayan, I., & Pynoos, R. S. (2020). 25-year follow-up of treated and not-treated adolescents after the Spitak earthquake: course and predictors of PTSD and depression. Psychological Medicine, 14, 1–13. Advance online publication. https://doi.org/10.1017/S0033291719003891.Google Scholar
Grabe, H. J., Spitzer, C., Schwahn, C., Marcinek, A., Frahnow, A., Barnow, S. , ….& Rosskopf, D. (2009) Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. American Journal of Psychiatry, 166, 926–933.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), 3029–3038.Google Scholar
Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5HTTLPR), stress, and depression meta-analysis revisited. Archives of General Psychiatry, 68, 444–454.Google Scholar
Koenen, K. C., Lyons, M. J., Goldberg, J., Simpson, J., Williams, W. M., Toomey, R., … & Tsuang, M. T. (2003). A high-risk twin study of combat-related PTSD comorbidity. Twin Research, 6 (3), 218–226. https://doi.org/10.1375/136905203765693870.Google Scholar
Koenen, K. C. , Fu, Q. J. , Ertel, K., Lyons, M. J., Eisen, S. A., True, W. R., Goldberg, J., & Tsuang, M. T. (2008). Common genetic liability of major depression and posttraumatic stress disorder in men. Journal of Affective Disorders, 105, 109–115.CrossRefGoogle ScholarPubMed
Lange, K., & Boehnke, M. (1983). Extensions to pedigree analysis. IV. Covariance components models for multivariate traits. American Journal of Medical Genetics, 14 (3), 513–524.CrossRefGoogle ScholarPubMed
Li, G., Wang, L., Cao, C. , Fang, R. , Hall, B. J. , Elhai, J. D. , & Liberzon, I. (2021). Post-traumatic stress symptoms of children and adolescents exposed to the 2008 Wenchuan earthquake: a longitudinal study of 5-HTTLPR genotype main effects and gene-environment interactions. International Journal of Psychology, 56 (1), 22–29.Google Scholar
Logue, M. W., Baldwin, C., Guffanti, G., Melista, E., Wolf, E. J., Reardon, A. F., … & Koenen, K. (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), 937–942.Google Scholar
Logue, M. W., Miller, E. J., Wolf, E.J., et al. (2020). Traumatic Stress Brain Study Group. An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci. Clinical Epigenetics, 12 (1), 46.Google Scholar
Lyons, M. J., Goldberg, S. A., Eisen, S. A, et al. (1993). Do genes influence exposure to trauma? A twin study of combat. American Journal of Medical Genetics, 48 (1), 22–27.Google Scholar
Mellman, T., Alim, D. D., Brown, E., Gorodetsky, B., et al. (2009). Serotonin polymorphisms and posttraumatic stress disorder in a trauma-exposed African American population. Depression and Anxiety, 26, 993–997.CrossRefGoogle Scholar
Nguyen, A., Rauch, T. A., Pfeifer, G. P., et al. (2010). Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. The Journal of the Federation of American Societies for Experimental Biology, 24 (8), 3036–3051.CrossRefGoogle Scholar
Nievergelt, C. M., Maihofer, A. X., Klengel, T., et al. (2019). International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nature Communications, 10 (1), 4558.CrossRefGoogle ScholarPubMed
Noble, E. P., Blum, K., Khalsa, M. E. (1991). Allelic association of the D2 dopamine receptor gene with receptor binding characteristics in alcoholism. Archives of General Psychiatry, 48, 648–654.CrossRefGoogle ScholarPubMed
Ruskin, J., Rasul, R., Schneider, S., et al. (2018). Lack of access to medical care during hurricane Sandy and mental health symptoms. Preventive Medicine Reports, 10, 363–369. https://doi.org/10.1016/j.pmedr.2018.04.014.CrossRefGoogle ScholarPubMed
Segman, R. H., Cooper-Kazaz, F., Macciardi, F., et al. (2002). Association between the dopamine transporter gene and posttraumatic stress disorder. Molecular Psychiatry, 7 (8), 903–907.CrossRefGoogle ScholarPubMed
Sharma, A., & Kar, N. (2019). Posttraumatic stress, depression, and coping following the 2015 Nepal earthquake: a study on adolescents. Disaster Medicine and Public Health Preparedness, 13, 236–242.Google Scholar
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, 2002; 159 (10): 1675–1681.Google Scholar
Steinberg, A. M, Brymer, M. J., Kim, S., Ghosh, C., Ostrowski, S. A., Gulley, K., Briggs, E. C., & Pynoos, R. S. (2013). Psychometric properties of the UCLA PTSD Reaction Index: Part 1. Journal of Traumatic Stress, 26, 1–9.Google Scholar
Terwilliger, J. D., & Göring, H. H. (2000). Gene mapping in the 20th and 21st centuries: statistical methods, data analysis, and experimental design. Human Biology, 72 (1), 63–132.Google ScholarPubMed
Thakur, G. A., Joober, R., & Brunet, A. (2009). Development and persistence of posttraumatic stress disorder and the 5-HTTLPR polymorphism. Journal of Traumatic Stress, 22, 240–243.CrossRefGoogle ScholarPubMed
True, W. J., Rice, J., Eisen, S. A., Heath, A. C., Goldberg, J., & Lyons, M. J. (1993). A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Archives of General Psychiatry, 50, 257–264.CrossRefGoogle ScholarPubMed
Van Den Bogaert, A., Sleegers, K., De Zutter, S., Heyrman, L., Norrback, K. F., Adolfsson, R., Van Broeckhoven, C., & Del-Favero, J. (2006) Association of brain-specific tryptophan hydroxylase, TPH2 with unipolar and bipolar disorder in a northern Swedish, isolated population. Archives of General Psychiatry, 63, 1103–1110.Google Scholar
Vermetten, E., Schmahl, S., Southwick, S. M., & Bremner, J. D. (2007). A positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder. Psychopharmacology Bulletin, 40 (1), 8–30.Google ScholarPubMed
Wurtman, R. J. (2005). Genes, stress, and depression. Metabolism, 54 (5 Suppl. 1), 16–19.Google Scholar
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), 656–663.Google Scholar
Young, R. M., Lawford, B. R., Noble, E. P., Kann, B., Wilkie, A., Ritchie, T., Arnold, L., & Shadforth, S. (2002). Harmful drinking in military veterans with post-traumatic stress disorder: association with the D2 dopamine receptor A1 allele. Alcohol and Alcoholism, 37 (5), 451–454.CrossRefGoogle ScholarPubMed
Zill, P., Baghai, T. C., Zwanzger, P., Schüle, C., Eser, D., Rupprecht, R., Möller, H. J., Bondy, B., & Ackenheil, M. (2004). SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression. Molecular Psychiatry, 9, 1030–1036.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×