Vulnerability to Traumatic Stress

Posttraumatic stress disorder, PTSD, is a logical place to start the discussion of human response to traumatic stress, since it is a condition that is a manifestation of prior stress. However PTSD has its own characteristic genetic predisposition and unique biological composite. Individuals with PTSD apparently share genetic markers that are predictive for the cluster of symptoms that characterize PTSD. There seems to be a role for the dopamine D2 receptor gene, DRD2 A1+ allele. This gene has been associated with reduced D2 mesolimbic dopamine receptor binding and increased somatic concerns, anxiety or insomnia, social dysfunction and harm avoidance, and depression (Lawford, Young, Noble, Kann, Arnold, Rowell, & Ritchie, 2003). Patients with PTSD also tend to have higher frequencies of the (serotonin-transporter-linked polymorphic region) SERTPR s/s genotype (Lee, Lee, Kang, Kim, Kim, Kee, et al. 2005). Early and chronic neurobiological alterations in synaptic neurotransmitter transporters in discrete regions of the brain involved in processing relational and contextual aspects of stressful experiences like traumatic memory along with concurrent stress and reactive neurohormonal cascade to prior stressful events may possibly underlie and allow for respective gene expression of the disorder (Meaney, 2001).

A genetic component for PTSD has also been supported in twin studies. Monozygotic twins are more likely to develop the PTSD cluster of symptoms of intrusive reexperiencing, avoidance, numbing anesthesia in response to traumatic stress than other related siblings (Stein, Jang, Taylor, Vernon, & Livesley 2002). Furthermore both PTSD symptomatic trauma exposed-unexposed twins have been found to have significantly smaller right hippocampal volumes when compared with asymptomatic trauma exposed-unexposed twins (Gilbertson, Shenton, Ciszewski, Kasai, Lasko, Orr, & Pitman, 2002). The unexposed PTSD twin might carry the genetic vulnerability for PTSD symptom expression. The condition remains unexpressed for lack of trauma exposure but is more apt to develop in response to traumatic stress (Segman & Shalev, 2003). This as a diasthesis model suggests a genetic component and vulnerability that reduces an individual’s resiliency and increased vulnerability for developing later PTSD and its cluster of symptoms in response to traumatic experience.

Unaffected siblings like their parents with PTSD present a trend for increased glucocorticoid sensitivity (Yehuda, Halligan, & Bierer, 2002). PTSD is accompanied by increased plasma (Yehuda, Lowy, Southwick, Shaffer, & Giller, 1991) and urinary (Yehuda, Boisoneau, Mason, & Giller, 1993) lymphocyte glucocorticoid receptor (GR) levels and lower serum and salivary cortisol levels in combat veterans (Boscarino, 1996) when compared with depressed and control populations. Both norepinephrine (NE) and stress activated hormone, corticotropin releasing hormone (CRH) cerebrospinal fluid (CSF) levels are elevated in combat vets with PTSD symptoms (Bremner, Licinio, Darnell, Krystal, Owens, Southwick, et al., 1997; Baker, West, Nicholson, Ekhator, Kasckow, Hill et al., 1999; Geracioti, Baker, Ekhator, West, Hill, Bruce et al., 2001) suggesting some degree of hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Women symptomatic for PTSD and with histories of childhood sexual abuse present altered afternoon plasma cortisol levels and in response to exogenous CRF challenge present blunted pituitary ACTH response when compared with asymptomatic abuse survivors (Bremner, Vythilingam, Anderson, Vermetten, McGlashan, Heninger et al., 2003). Exogenous steroid dexamethasone (DEX) challenge induces an exaggerated plasma super-suppression of the steroid in adult trauma survivors (e.g. combat veterans and Holocaust survivors) symptomatic for PTSD when compared with weaker suppression levels in PTSD survivors with comorbid major depression, asymptomatic survivors, and healthy controls (Grossman, Yehuda, New, Schmeidler, Silverman, Mitropoulou, et al., 2003; Yehuda, Southwick, Krystal, Bremner, Charney, & Mason, 1993; Yehuda, Boisoneau, Lowy, & Giller, 1995) again reflecting alterations in HPA reactivity. PTSD has a condition-specific neurohormonal response that characterizes it.

However not everyone one exposed to traumatic stress goes onto to later develop the condition. Most trauma victims (94%) within the first two weeks of traumatic exposure will develop one or more PTSD symptoms of unwanted reexperiencing of emotionally charged sensory aspects of the trauma, avoidance of trauma-related cues, and generalized hyperarousal (Rothbaum, Foa, Murdock, Riggs, & Walsh, 1992). Normally symptoms resolve expression after the first few months. Decreases in rated PTSD symptom expression from 65% to 47% (Rothbaum et al., 1992) and 34.4% to 23.58% (Ursano, Fullerton, Epstein, Crowley, Kao, Vance et al., 1999) have been reported at one and three months. Another report documented rated decreases from 29.9% to 19.0% at one and four months post trauma respectively (Shalev, Freedman, Peri, Brandes, Sahar, Orr et al., 1998). Moreover rates of PTSD symptom expression continue to decrease thereafter, from 18.2% to 14.0% at six to twelve months post trauma (Ursano et al., 1999). In contrast another study reported that 6.2% of survivors who did not meet PTSD diagnosis at three months met diagnostic criteria at one year post-trauma (Ehlers, Mayou, & Bryant, 1998). These findings generally suggest that early transient PTSD symptoms evolve and spontaneously resolve without intervention for most individuals exposed to various degrees of traumatic stress. Yet there are also some individuals noted earlier who will have a delayed response to trauma and will go on to develop the condition during the later post-trauma period.

Despite documented genetic predispositions, cumulative developmental trauma (emotional pain experienced in response to breached expectation from ontogenetically social motivational need fulfillment) and both early and later experienced trauma disrupts memory processing and sometimes produces post-traumatic stress disordered (PTSD) symptom expression in the genetically predisposed individual with genetically predisposed vulnerability for later developing the condition. Individuals who go onto to develop PTSD symptom expression typically seek trauma avoidance coping mechanisms due to the perceived intensity of emotional pain experienced with trauma retrieval. Despite the relief with trauma avoidance, the cup runs over so to say (i.e. a response threshold or response constraint is exceeded) and produces symptoms of sleep disturbance, nightmares, abreactions (reexperiencing uncontrollable painful sensory flashbacks of the trauma as if it were happening in the present), diffuse anxiety (reminiscent of constrained fear), and depression (reminiscent of the sense of loss of integrity in response to the trauma), and unintentional identification with the trauma. Freud called the warehouse and storage for avoided memory, the unconscious, and the process mediating its storage, repression. Recent neuroscience research suggests that this memory gets trapped in brain structures relating to encoding and storage and is awaiting retrieval. However, adaptive coping mechanisms of avoidance restrict neural components of the traumatic memory and get trapped within brain structures associated with storage. In order to facilitate symptom relief, the trauma survivor will need to retrieve the trauma and all the personally meaningful emotion and cognition associated with the trauma to facilitate the extinction of chronic traumatic physiological arousal associated with the trapped PTSD memory.

References

Baker, D.G., West, S.A., Nicholson, W.E., Ekhator, N.N., Kasckow, J.W., Hill, K.K., Bruce, A.B., Orth, D.N., & Geracioti, T.D. Jr. (1999). Serial CSF corticotropin-releasing hormone levels and adrenocortical activity in combat veterans with posttraumatic stress disorder. American Journal of Psychiatry, 156(4): 585-588.

Boscarino, J.A. (1996). Posttraumatic stress disorder, exposure to combat and lower plasma cortisol among Vietnam veterans: findings and clinical implications. Journal of Consulting and Clinical Psychology, 64(1): 191-201.

Bremner, J.D., Licinio, J., Darnell, A., Krystal, J.H., Owens, M.J., Southwick, S.M., Nemeroff, C.B., & Charney, D.S. (1997). Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder. American Journal of Psychiatry, 154(5): 624-629.

Bremner, J.D., Vythilingam, M., Anderson, G., Vermetten, E., McGlashan, T., Heninger, G., Rasmusson, A., Southwick, S.M., & Charney, D.S. (2003). Assessment of the hypothalamic-pituitary-adrenal axis over a 24 hour diurnal period and in response to neuroendocrine challenges in women with and without childhood sexual abuse and posttraumatic stress disorder. Biological Psychiatry, 54(7): 710-718.

Ehlers, A., Mayou, R.A., Bryant, B. (1998). Psychological predictors of chronic posttraumatic stress disorder after motor vehicle accidents. Journal of Abnormal Psychology, 107(3), 508-519.

Geracioti, T.D. Jr., Baker, D.G., Ekhator, N.N., West, S.A., Hill, K.K., Bruce, A.B., Schmidt, D., Rounds-Kugler, B., Yehuda, R., Keck, P.E. Jr., & Kasckow, J.W. (2001). CSF norepinephrine concentrations in posttraumatic stress disorder. American Journal of Psychiatry, 158(8): 1227-1230.

Gilbertson, M.W., Shenton, M.E., Ciszewski, A., Kasai, K., Lasko, N.B., Orr, S.P., & Pitman, R.K. (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature Neuroscience, 5(11), 1242-1247.

Grossman, R., Yehuda, R., New, A., Schmeidler, J., Silverman, J., Mitropoulou, Sta- Maria, N., Golier, J., & Siever, L. (2003). Dexamethasone suppression test findings in subjects with personality disorders: associations with posttraumatic stress disorder and major depression. American Journal of Psychiatry, 160: 1291-1298.

Lawford, B.R., McD Young, R., Noble, E.P., Kann, B., Arnold, L., Rowell, J., & Ritchie, T.L. (2003). D2 dopamine receptor gene polymorphism: paroxetine and social functioning in posttraumatic stress disorder. European Neuropsychopharmacology, 13(5), 313-320.

Lee, H.J., Lee, M.S., Kang, R.H., Kim, H., Kim, S.D., Kee, B.S., Kim, Y.H., Kim, Y.K., Kim, J.B., Yoon, B.K., Oh, K.S., Oh, B.H., Yoon, J.S., Lee, C., Jung, H.Y., Chee, I.S., & Paik, I.H. (2005). Influence of the serotonin transporter promoter gene polymorphism on susceptibility to posttraumatic stress disorder. Depression and Anxiety, 21(3), 135-139.

Meaney, M.J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review in Neuroscience, 24, 1161-1192.

Rothbaum, B.O., Foa, E.B., Murdock, T., Riggs, D., & Walsh, W. (1992). A prospective examination of post-traumatic stress disorder in rape victims. Journal of Traumatic Stress, 5, 455-475.

Segman, R.H., & Shalev, A.Y. (2003). Genetics of posttraumatic stress disorder. CNS Spectrum, 8(9), 693-698.

Shalev, A.Y., Freedman, S., Peri, T., Brandes, D., Sahar, T., Orr, S.P., & Pitman, R.K. (1998). Prospective study of posttraumatic stress disorder and depression following trauma. American Journal of Psychiatry, 155(5), 630-637.

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), 1675-1681.

Ursano, R.J., Fullerton, C.S., Epstein, R.S., Crowley, B., Kao, T.C., Vance, K., Craig, K.J., Dougall, A.L., & Baum, A. (1999). Acute and chronic posttraumatic stress disorder in motor vehicle accident victims. American Journal of Psychiatry, 156(4), 589-595.

Yehuda, R., Boisoneau, D., Mason, J.W., & Giller, E.L. (1993). Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders. Biological Psychiatry, 34(1-2): 18-25.

Yehuda, R., Boisoneau, D., Lowy, M.T., & Giller, E.L. Jr. (1995). Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder. Archives of General Psychiatry, 52(7): 583-93.

Yehuda, R., Halligan, S.L., & Bierer, L.M. (2002). Cortisol levels in adult offspring of Holocaust survivors: Relation to PTSD symptom severity in the parent and child. Psychoneuroendocrinology, 27, 171-180.

Yehuda, R., Lowy, M.T., Southwick, S.M., Shaffer, D., & Giller, E.L. Jr. (1991). Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder. American Journal of Psychiatry, 499-504.

Yehuda, R., Southwick, S.M., Krystal, J.H., Bremner, D., Charney, D.S., & Mason, J.W. (1993): Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder. American Journal of Psychiatry, 150(1): 83-86.