Stress reactivity after traumatic brain injury: implications for comorbid post-traumatic stress disorder

Abstract

Most people have or will experience traumatic stress at some time over the lifespan, but only a subset of traumatized individuals develop post-traumatic stress disorder (PTSD). Clinical research supports high rates of traumatic brain injury (TBI)-PTSD comorbidity and demonstrates TBI as a significant predictor of the development of PTSD. Biological factors impacted following brain injury that may contribute to increased PTSD risk are unknown. Heightened stress reactivity and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function are common to both TBI and PTSD, and affect amygdalar structure and function, which is implicated in PTSD. In this review, we summarize a growing body of literature that shows HPA axis dysregulation, as well as enhanced fear and amygdalar function after TBI. We present the hypothesis that altered stress reactivity as a result of brain injury impacts the amygdala and defense systems to be vulnerable to increased fear and PTSD development from traumatic stress. Identifying biological mechanisms that underlie this vulnerability, such as dysregulated HPA axis function, may lead to better targeted treatments and preventive measures to support psychological health after TBI.

Figures

Figure 1.

Effect of mild and moderate CCI and sham injury on HPA responsiveness to 30-min restraint stress on days 7, 34, and 70 post-injury. On days 7 and 34, tail vein samples were collected for plasma corticosterone (mean ± SEM) at baseline (time=0) and at 30, 60 and 90 min after stress onset. On day 70, trunk blood was obtained at the end of the 30-min stress period. a, p