The Root Cause of Post-Traumatic and Developmental Stress Disorder (Phase 1)
Abstract
Our overarching scientific hypothesis holds that serotonergic influences on brain development driven by genetics and early experience induce a variationof normal brain anatomy that makes the brain highly susceptible to the effects of severe stress. Previous findings from our lab support the existence of an anatomical phenotype related to the 5HTTLPR serotonin transporter genetic variant that confers susceptibility to depression, and the current work seeks to extend these findings to PTSD. Initial animal studies confirmed that this serotonin phenotype may affect fear-related behavior by alteringneurotransmission in subcortical circuits that include the amygdala. Low serotonin tone was associated with accentuated fear behavior, and we determined that glutamate neurotrtansmission in the basolateral amygdal was a critical element of this response. Preliminary studies support reduced serotonin fiberdensity in the human thalamus (upstream of the amygdala) in 5HTTLPR-s carriers, consitant with our animal study. In another important region immediately upstream from the amygdala, the medio-orbital prefrontal cortex, we have observed signs of accelerated aging in PTSD, and confimed that consistent with animal models, there is evidence for a reduction in dendritic spine density in PTSD. These findings are among the first post-mortemstudies of PTSD ever published. In addition to these scientific findings, our consortium is currently studying over 50 PTSD and similar numbers of MDD and control brains, including 40 brains collected with funding from this project. These brains are now linked with the National Center for PTSD Bank,which has great potential to contribute to future research efforts to understand the pathophysiology of PTSD and other stress-related disorders.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2015
- Accession Number
- AD1007711
Entities
People
- Keith A. Young
Organizations
- Texas A&M University