Psychotherapy and Neuroscience

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.


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