War, natural disasters, interpersonal violence, and other causes of trauma continue to plague our world. As a result, epidemiological studies have found worldwide lifetime prevalence rates for posttraumatic stress disorder as high as 20.4% for women and 8.2% for men.1 To help prevent and treat the negative consequences of trauma, psychiatry continues to not only study the consequences of trauma, but also the genetic and psychosocial influences on developing PTSD.
Armen K. Goenjian, MD, LDFAPA, FACGS, research psychiatrist at the David Geffen School of Medicine at University of California, Los Angeles, is doing just that. Goenjian and colleagues have been conducting ongoing research among survivors of the devastating 1988 6.9 earthquake in Armenia. Their work is one of the first long-term studies of survivors of a natural disaster who experienced posttraumatic stress disorder five or more years after the event. Psychiatric Times invited Dr Goenjian to discuss their latest findings.
Psychiatric Times: In this most recent study,2 you found a significant number of patients still had depressive and PTSD symptoms 25 years after the initial trauma. What else did you learn?
Armen Goenjian, MD: The study found that severe adversities following a catastrophic disaster with high morbidity, mortality, and destruction could result in chronic PTSD and depressive symptoms among a significant portion of the exposed population (9% to 22%). These findings represent an ongoing public health problem that requires strategies across service settings to better identify this vulnerable population and provide needed services.
We also learned that there was an enduring impact of trauma-grief focused intervention at 1.5 years post-earthquake; the school-based screening and treatment program that we initiated benefited a generation of adolescents as they transitioned to adulthood. Additionally, the findings suggested that alleviating post-disaster adversities, improving the social ecology, and monitoring chronic medical illnesses should be considered essential components of recovery programs.
With rampant gun violence in our communities, an increase of weather-related catastrophic disasters all over the globe, ongoing political violence, and victims of sexual and other abuse, these findings are important and relevant to future research and treatment programs.
PT: Based on your previous research, did these latest findings surprise you?
Goenjian: Our previous work included two follow-up studies among students (early adolescents). The first was a 1.5- and 3-year follow-up of another group of treated and untreated adolescents.3 The second study was a 1.5- and 5-year follow-up of participants (this patient population is included in our 25-year follow-up study).4 In the studies, participants received trauma/grief-focused group and individual psychotherapy for six weeks. Both studies found enduring benefits for treating PTSD and depressive symptoms.
There were a few striking findings, in addition to the fact that the treatment benefits were retained over the 25 years. What was really intriguing was the reversal of the depression pattern at 25-year follow-up. The level of depression among the untreated participants from Gumri city was significantly lower at 1.5 years, but at 25 years, the reverse occurred. The level of depression was lower among the untreated participants from Spitak city, in which there were more deaths and destruction at the time of the earthquake and the level of depression was significantly higher at 1.5 years. The higher level of post-earthquake adversities, lack of housing, higher unemployment, and poverty in Gumri explained the unexpected elevated levels of depression in Gumri.
PT: A few years ago, you explored the genetic factors that affect the risk of developing PTSD. Which genes were most closely linked to developing PTSD?
Goenjian: One of the consistent findings in the genetics of PTSD is the heritability of PTSD vulnerability,5 and we wanted to further explore this notion among Armenians in the earthquake zone. Unlike the veterans in the True et al. study,5 the population in northern Armenia is substantially less heterogeneous because they come from the same ethnic group. Additionally, the earthquake presented a unique opportunity—potentially confounding exposure variables were minimized because family members were exposed to the same type of trauma at the same time and with similar trauma severities.
Because of the availability of multi-generational (3 to 5) families who were exposed to traumatic events at the time of the earthquake, we used a family study design. Family studies reduce genetic heterogeneity, because there is an increased likelihood of affected family members having the same causal genetic variants compared to case-controlled studies, in which every case could potentially have a unique causal genetic variant. The heritability in our study was 42%.6
After determining the heritability, we looked for candidate genes. We found carriers of certain variants of tryptophan hydroxylase (TPH1 and TPH2) genes were at risk for PTSD. Similarly, we found carriers of an allele of catechol-O-methyltransferase (COMT) were also at risk for PTSD. TPH genes encode for TPH, the rate-limiting enzyme for the synthesis of serotonin. COMT has broad biological functions including regulation of catecholamines (e.g., dopamine) and enkephalins.
PT: Are the genes associated with PTSD risk also associated with other psychiatric disorders?
Goenjian: Indeed, we studied the genetic correlation of PTSD and depression and anxiety and found that they shared genetic disposition. We expect some genes also to be associated with other disorders. For example, in a study among Taiwanese women,7 Sun and colleagues found an association between major depression and the same TPH1 gene variant that we identified. And, in a Swedish study,8 Van Den Bogaert et al. found an association between the TPH2 gene and unipolar depression. A few other studies have found an association of variants of COMT gene with anxiety, depression, and PTSD.
1. Bryant RA. Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges. World Psychiatry. 2019;18(3):259-269.
2. Goenjian A, Steinberg A, Walling D, et al. 25-year follow-up of treated and not-treated adolescents after the Spitak earthquake: course and predictors of PTSD and depression. Psychol Med. 2020;14:1-13.
3. Goenjian AK, Karayan I, Pynoos RS, et al. Outcome of psychotherapy among early adolescents after trauma. Am J Psychiatry. 1997;154(4):536-42.
4. Goenjian AK, Walling D, Steinberg AM, et al. A prospective study of posttraumatic stress and depressive reactions among treated and untreated adolescents 5 years after a catastrophic disaster. Am J Psychiatry. 2005;162(12):2302-8.
5. True WJ, Rice J, Eisen SA, et al. A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Arch Gen Psychiatry. 1993;50(4):257-64.
6. Goenjian AK, Noble EP, Walling DP, et al. Heritabilities of symptoms of posttraumatic stress disorder, anxiety, and depression in earthquake exposed Armenian families. Psychiatr Genet. 2008;18(6):261-6.
7. Sun HS, Tsai HW, Ko HC, et al. Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese women. Genes Brain Behav. 2004;3(6):328-36.
8. Van Den Bogaert A, Sleegers K, De Zutter S, et al. Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated population. Arch Gen Psychiatry. 2006;63(10):1103-10.
9. Goenjian AK, Najarian LM, Pynoos RS, et al. Posttraumatic stress reactions after single and double trauma. Acta Psychiatr Scand. 1994;90(3):214-21.
10. Goenjian AK, Steinberg AM, Najarian LM, et al. Prospective study of posttraumatic stress, anxiety, and depressive reactions after earthquake and political violence. Am J Psychiatry. 2000 Jun;157(6):911-6.