Susceptible versus Resilient

Post-traumatic stress disorder (PTSD) is an example of the brain “gone wrong” after trauma. We once called it “shell shock,” but it afflicts more than just soldiers. Most people experience a traumatic event at some time during their life, an event perceived as life threatening (e.g., witnessing a deadly car crash or seeing a fellow soldier killed in battle). Most people experience temporary distress, like bad dreams or bouts of crying. They eventually “get over it,” and it never impairs their ability to carry on with life. Some, however, experience worse symptoms. We don’t know for sure, but from 8 to 18% of the population have sudden “flashbacks,” dissociating them from whatever is going on now; a car backfire and suddenly scares them; they freeze. They have frequent nightmares, are often moody and “distant,” even from loved ones. They have PTSD…and it lasts a lifetime.

We all respond to trauma in the same way. The brain goes into “alert mode,” our “stress response,” activating the hippocampal-pituitary-adrenal (HPA) axis. The hypothalamus releases corticotropin releasing hormone (CRH) and arginine vasopressin (AVP), which together cause the pituitary to release adrenalin (adrenocorticotropic hormone, ACTH). Having global effects, the hormones reach the amygdala, our “memory center.” Finally (in a matter of seconds, though), the adrenal cortex releases glucocorticoids, the most common being cortisol. That heightens the sympathetic nervous system, changes the senses needed to respond quickly to perceived threat. We’re ready for “flight or fight.” However, cortisol “loops back” and dampens the release of CRH, eventually returning the stress response system to its normal state (called “negative feedback”).

The stress response system is adaptive; that is, it evolved via natural selection, is “good for us.” We are resilient to stress. But if it’s good for us, why is bad for some people? That is, why are some people resilient to trauma, while others are susceptible to PTSD?

We don’t have a complete answer, but we can “see” differences in the brains of resilient versus susceptible people (“seeing” means post mortem assays, self-report diaries, brain scans, and animal studies). The HPA axis of PTSD sufferers is dysfunctional, producing too little of the hormones needed for “negative feedback” and a return to normal. Moreover, the amygdala and its memory functions are not normal, are less able to form new memories while being overwhelmed by memories of the trauma.

Going deeper in the brain, we find that most PTSD sufferers have single nucleotide polymorphisms (SNPs) in several genes key to HPA axis function: FKBP5, NR3C1, CRHR1, and CRHR2. Their genes (“alleles”) are different. However, some people have these SNPs but don’t suffer PTSD after trauma. Additionally, many with PTSD experienced childhood abuse. Thus, we have a strong case suggesting that PTSD represents a gene-by-environment (G x E) interaction. Early childhood abuse “triggers” those alleles, altering the HPA axis so it is dysfunctional when experiencing adult trauma.

Clarence A. “Sonny” Williams

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