Mechanisms of Vulnerability to PTSD: The Role of Early Life Stressors

Apr 08, 2015

It is understandable that a trauma experienced early in life could leave psychological scars, making it more difficult for the same individual to recover from a subsequent trauma later in life. In fact, scientific studies have shown an association between early life events and later susceptibility to posttraumatic stress disorder.

But can traumatic events in our childhood leave more than psychological scars? Could they also leave physical “scars,” perhaps by altering the expression of one or more of our genes, creating a biological reason why one individual might be more susceptible to PTSD than another? And if that is the case, could a drug therapy be developed to counter or reverse that biological disturbance? Could that therapy then be used to help prevent or treat PTSD?

These are questions being posed by Randy Strong, PhD and his collaborators, David Morilak, PhD, and Alan Frazer, PhD, of the University of Texas Health Science Center at San Antonio as they conduct a STRONG STAR preclinical investigation on the role of early life stressors and mechanisms of vulnerability to PTSD.

The hypothesis

Although every person who suffers from PTSD has experienced a traumatic stress, the majority of trauma-exposed persons do not develop PTSD, leading researchers to question what unique characteristics of PTSD patients impair the normal recovery process. This study is investigating one possibility, testing the hypothesis that early life stressors cause alterations in the expression of genes, specifically genes that regulate hypothalamic pituitary adrenal (HPA) axis activity, and that these changes increase a person’s susceptibility to PTSD following another traumatic event later in life. The HPA axis is an important component of the neuroendocrine system that regulates several bodily functions, including response to stress.

The hypothesis being tested by this study is based on findings from preclinical studies in which a chemical process called DNA methylation was used in rats to program the activity of genes regulating HPA activity in response to early life events, such as differences in maternal care or in pre- and perinatal exposure to a type of steroids called glucocorticoids. Observations reveal that these experimental animal models mimic processes observed in humans in whom early life events are associated with the development of PTSD. Moreover, the programming of changes in the HPA axis in experimental models is strikingly similar to the effects on the HPA axis described in PTSD. Thus, these studies may provide a molecular link between early environment and gene expression. Most importantly, preclinical studies suggest that these epigenetic changes may be reversed or prevented by pharmacological treatment with serotonergic drugs such as SSRIs, histone deacetylase inhibitors, and methyl donors.

The experiment

In a preclinical study for STRONG STAR, Drs. Strong, Morilak and Frazer are looking at the impact of pre- and perinatal stressors in Sprague-Dawley rats when paired with a second experimental stressor in adulthood. In particular, they are observing physiological and neurochemical changes and various aspects of behavior, such as whether the animals show an active or passive coping behavior when presented with a challenge or mildly stressful situation. Other behavioral measures correspond with the types of behaviors seen in humans with PTSD, such as the tendency to withdraw from social groups, hyper-arousal, and avoidance of certain situations. The research team is also observing the treatment effects of the SSRI sertraline in rats that exhibit symptomatic behaviors. From these investigations, they expect to learn more about how early life stress impacts one’s vulnerability to PTSD in adulthood and whether serotonegic drugs can be used to prevent or reverse epigenetic risk factors for the disorder.