Traumatic Stress Studies Division

Research Studies and Findings

Many of our programs are funded by national agencies such as the National Institute of Mental Health and the Department of Veterans Affairs. Our programs are designed to gain a better scientific understanding of the biology of stress reactions, and how to treat them better. Through this funded research we have been able to gain a better understanding of posttraumatic stress disorder (PTSD) and stress responses.

The Stress Response

When confronted with extreme stress, the body initiates many chemical reactions to facilitate a quick escape from stress. The amygdala is the brain region that alerts the body to danger and activates hormonal systems. Activation of the hormones noradrenaline and adrenaline results in accelerated breathing, pulse, and heart rate, and increased release of energy to muscles and other organs, which literally helps people run faster from stress or mobilize a response that requires coping with the stressor head-on. Once the immediate danger has passed, other hormones, particularly the hormone cortisol, help terminate stress-activated reactions. Usually, the more stress there is, the more cortisol is needed to contain the stress response. Our work has demonstrated that trauma survivors with PTSD have higher levels of noradrenaline^1,2 and lower levels of the hormone cortisol.^3,4,5

Hormonal Studies of Trauma Survivors

Since cortisol ultimately reduces the body’s stress responses, having diminished levels of this hormone during stress may interfere with the body’s ability to restore itself fully in the aftermath of a trauma. Indeed, a major problem for trauma survivors is that they continue to experience the world as if it is still dangerous. Many continue to react to fairly non-dangerous signals in the environment in an exaggerated way that would be far more appropriate if there were a life threat. The exaggerated physical reactions to stress in the aftermath of a traumatic event appear to be related to this altered hormonal balance that is in part a result of the traumatic event.

It has been particularly interesting to us that cortisol levels are low in PTSD, since levels of this hormone are elevated in major depressive disorder, a condition that shares many symptoms with PTSD. Because of this phenomenon, we believe it may be possible to distinguish between people with a posttraumatic stress reaction and those with major depression on the basis of hormone levels. More importantly, we believe that the specific hormonal alterations in PTSD support the theory that this condition requires specialized treatments.

Recent Observations

• We have observed low urinary or plasma cortisol levels in Persian Gulf War veterans,⁶ Vietnam veterans,^3,4 Korean War and World War II veterans, Holocaust survivors,⁵ adolescents exposed to earthquake,⁷ and adult survivors of childhood sexual abuse⁸ with PTSD compared to levels in similarly-exposed trauma survivors without PTSD and nonexposed comparison subjects. We have also observed that cortisol is low in rape victims⁹ and motor vehicle accident victims¹⁰ in the immediate aftermath of these events. In contrast, we and others have observed high levels of cortisol in persons with major depression.³
• Although cortisol levels appear to remain lower in trauma survivors with PTSD, there are also subtle changes in the pattern of hormone release over a 24-hour period.¹¹ Furthermore, there are important age-related changes in the pattern of cortisol release in PTSD.
• Cortisol levels appear to be lower in trauma survivors who are at risk or who develop PTSD compared to in those who will not develop PTSD following exposure to a traumatic event.^9,10 In the future, it may be possible to determine who is at risk for developing PTSD based on the biological changes at the time of the traumatic event.
• While cortisol levels are lower in trauma survivors with PTSD, cortisol receptors, which confer biological activity to cortisol, appear to be more sensitive. Trauma survivors with PTSD show more sensitive responses following administration of low doses of the synthetic cortisol, dexamethasone,^12,13,14 and the cortisol synthesis inhibitor, metyrapone.¹⁵
• Low cortisol levels may be related to risk for PTSD. In one study, rape victims with a prior history of trauma had lower cortisol levels in the immediate aftermath of trauma (i.e., within hours after the event) than those without such a history.^9,16 We have also observed low cortisol in children of Holocaust survivors, particularly those with the risk factor of parental PTSD.¹⁷
• There are important immune changes that may be associated with low cortisol and particularly, to the more sensitive cortisol receptors. These immune changes, in turn, may be related to the increased rate of physical illness in trauma survivors.¹⁸

Trauma survivors describe a wide range of memory problems. These problems range from having distressing and unwanted recollections of past traumatic events to being unable to remember important details about significant life experiences to experiencing difficulties in concentration and attention.

Studies of Memory

We initially observed that trauma survivors with PTSD performed differently on some tests of memory function compared to those who had not experienced trauma.¹⁹ These findings seemed important to us because they suggested that there might be changes in the brain regions that are involved in memory processing in PTSD.

We have continued our studies of memory performance in trauma survivors to learn more about how the brain processes information related to traumatization. It is becoming clear that people who have undergone traumatic experiences process information differently than those who have not experienced traumatic stress. By also evaluating brain structure using magnetic resonance imaging (MRI) and brain function using positron emission tomography (PET) we are able to evaluate the brain areas, such as the hippocampus, that may be involved in these memory changes. By simultaneously studying memory functioning and brain imaging we hope to understand better the biologic basis of the memory problems experienced by trauma survivors and to find improved ways of treating these symptoms.

Studies of Intergenerational Effects of Trauma and Risk for the Development of PTSD

We began our research on the intergenerational effects of trauma after hearing poignant descriptions from children of Holocaust survivors in our clinical program about their childhood experiences. Many offspring described feeling "traumatized" because of the Holocaust. Some adult children described the loneliness and isolation they felt growing up in households that were haunted by memories of murdered relatives. Some described the burden of feeling the need to compensate their parents for past losses. Some felt vulnerable, feeling that they were taught to fear the environment and react to it with inappropriate hypervigilance and distrust. Some talked about how their own life experiences felt diminished in contrast to their parents’ experiences in the Holocaust. Some reported feeling overwhelmed by the responsibility of caring for their impaired or distraught parent from a young age. Some adult children were reeling from what amounted to emotional or physical neglect. Many described experiencing symptoms that were comparable to those of their parents, and reported feeling quite distressed by their own stressful events.

We felt these descriptions warranted systematic investigation into the effects of the Holocaust on the adult children of survivors and began to evaluate their psychological and biological status. We felt it important to study not only the offspring who presented for treatment to our program, but also individuals from the community at large, some of whom had never sought mental health treatments, in order to obtain a representative sample. We believe that our findings apply not only to children of Holocaust survivors, but also to children of any trauma survivor, and are performing research studies to determine intergenerational effects in other groups.

Recent Observations

• Adult children of Holocaust survivors do not experience more traumatic life events than demographically-comparable Jewish adults, but they do report a greater number of non-traumatic but stressful life events and a greater degree of distress to these events.²⁶
• Adult children seem to have a greater prevalence of mood and anxiety disorders, including PTSD, than appropriate comparison subjects.²⁶
• There appears to be a greater prevalence of PTSD among offspring with two biological parents who were Holocaust survivors compared to those with only one Holocaust survivor parent.²⁷
• Offspring who have had PTSD are significantly more likely to have had parents with PTSD.²⁸ This suggests the possibility of a familial "transmission" of PTSD. It is not known how this transmission occurs; however, we are currently exploring the mechanisms by which it could occur.
• Adult children of Holocaust survivors, regardless of whether they themselves ever had PTSD, seem to demonstrate similar biological alterations to trauma survivors with PTSD. This provocative finding suggests that what may have been "transmitted" to the children of Holocaust survivors is a vulnerability to PTSD or stressful life events.¹⁷

References

1. Yehuda R, Southwick SM, Ma X, et al: Urinary catecholamine excretion and severity of symptoms in PTSD. J Nerv Men Dis, 180:321-325, 1992.
2. Yehuda R, Siever L, Teicher MH, et al. Plasma norepinephrine and MHPG concentrations and severity of depression in combat PTSD and major depressive disorder. Biol Psych, 44:56-63, 1998.
3. Yehuda R, Southwick SM, Nussbaum G, et al: Low urinary cortisol excretion in patients with PTSD. J Nerv Ment Dis, 178:366-309, 1990.
4. Yehuda R, Boisoneau D, Mason JW, Giller EL: Relationship between lymphocyte glucocorticoid receptor number and urinary-cortisol excretion in mood, anxiety, and psychotic disorder. Biol Psych, 34:18-25, 1993.
5. Yehuda R, Kahana B, Binder-Brynes K, et al: Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am J Psychiatry, 152:982-986, 1995.
6. Kellner M, Baker D, Yehuda R: Salivary cortisol in Desert Storm returnees. Biol Psych, 41: 849-850, 1997.
7. Goenjian AK, Yehuda R, Pynoos RS, et al. Basal cortisol and dexamethasone suppression of cortisol among adolescents after the 1988 earthquake in Armenia. Am J Psychiatry, 153: 929-934, 1996.
8. Stein MB, Yehuda R, Koverola C, Hanna C: HPA Axis functioning in adult Women who report experiencing severe childhood sexual abuse, Biol Psychiatry, 42:680-686, 1997.
9. Resnick HS, Yehuda R, Foy DW, Pitman R: Effect of prior trauma on acute hormonal response to rape. Am J Psychiatry, 152:1675-1677, 1995.
10. Yehuda R, Shalev AY, McFarlane AC. Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event. Biol Psych, 44:1305-1313, 1998.
11. Yehuda R, Teicher MH, Levengood R, et al: Cortisol regulation in posttraumatic stress disorder and major depression: A chronobiological analysis. Biol Psych, 40:79-88, 1996.
12. Yehuda R, Southwick SM, Krystal JM, et al: Enhanced suppression of cortisol following dexamethasone administration in combat veterans with PTSD and major depressive disorder. Am J Psychiatry, 150:83-86, 1993
13. Yehuda R, Boisoneau D, Lowy MT, Giller EL: Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without PTSD. Arch of Gen Psych, 52:583-593, 1995.
14. Goenjian AK, Yehuda R, Pynoos RS, et al. Basal cortisol and dexamethasone suppression of cortisol among adolescents after the 1988 earthquake in Armenia. Am J Psychiatry, 153: 929-934, 1996
15. Yehuda R, Levengood RA, Schmeidler RA, et al: Increased pituitary activation following metyrapone administration in PTSD. Psychoneuroendocrinology, 21: 1-16, 1996
16. Yehuda R, Resnick HS, Schmiedler H, et al. Predictors of cortisol and MHPG responses in the acute aftermath of rape. Biol Psych , 43:855-859, 1998
17. Yehuda R. Parental PTSD as a Risk Factor for PTSD, in Yehuda (Ed Risk Factors for Posttraumatic Stress Disorder. Progress in Psychiatry Series, American Psychiatric Association, Inc., 1999.
18. Yehuda R, Wong C, Rappaport MH. Hypothalamic-Pituitary-Adrenal Axis regulation of the immune system in Posttraumatic Stress Disorder. American College of Neuropsychopharmacology, 1999 Annual Meeting..
19. Yehuda R, Keefe RSE, Harvey P, et al: Learning and memory in combat veterans with posttraumatic stress disorder. Am J Psychiatry, 152: 137-139, 1995.
20. Yehuda R, Golier J, Harvey PD. Explicit and Implicit Memory in Holocaust Survivors with and without PTSD. Presentation at the 1999 meeting of the ACNP.
21. Golier J, Yehuda R, Cornblatt B, et al. Sustained attention in combat-related posttraumatic stress disorder. J Integr Psychophys, 32:52-61, 1997.
22. Golier J, Harvey P, Steiner A, Yehuda R: Source Monitoring in PTSD: In: Yehuda R, McFarlane AC (eds). Psychobiology of Posttraumatic Stress Disorder, Ann NY Acad Sci, Vol. 821472-475, 1997
23. Yehuda R, Elkin A, Schmeidler J, et al: Dissociation in aging survivors. Am J Psychiatry, 153:935-940, 1996.
24. Golier J, Yehuda R. Neuroendocrine alterations and memory related impairments in PTSD. Devel Psychopath, 1998;10:857-869
25. Yehuda R, Schmeidler J, Siever LJ, et al. Individual differences in PTSD symptom profiles in Holocaust survivors who were in concentration camps vs. hiding. J Traum Stress, 10: 453-465, 1997.
26. Yehuda R, Schmeidler J, Wainberg M, et al: Increased vulnerability to PTSD in adult offspring of Holocaust survivors. Am J Psychiatry, 155:1163-1172, 1998
27. Yehuda R, Schmeidler J, Giller E et al: Relationship between PTSD characteristics of Holocaust survivors and their adult offspring. Am J Psychiatry, 155:841-843, 1998.
28. Yehuda R, Schmeidler J, Aferiat DH, Breslau IG, Bierer LM, Dolan S: Low cortisol and risk for PTSD in adult offspring of Holocaust Survivors. Am J Psychiatry, submitted.