Trauma during early childhood is a major risk factor for the adult development of anxiety disorders such as post-traumatic stress disorder (PTSD). Determining the underlying causes of this relationship has remained extraordinarily challenging. In particular, determining how the functional state of the brain at the time of trauma contributes to PTSD and its neural underpinnings remains an elusive goal. Prior efforts, using animal models have mainly focused on maternal-separation procedures as early life stressors. We propose the use of painful foot shocks as a trauma procedure given that it is a major component of child abuse. This procedure when presented at different post-natal ages has yielded important insights into the ontogeny of fear learning. Our laboratory has substantial experience in adult fear conditioning, with the above procedure in the mature animal resulting in a life-long memory of the trauma that depends on the amygdala (AMY), hippocampus (HIPP) and prefrontal cortex (PFC). Importantly, if this fear experience is strong enough it results in a sustained vulnerability to over-exaggerate fear responses even to mild reminders of the original trauma. This sensitized fear response is a central characteristic of PTSD. Our approach identifies 3 key hypotheses based on the timing of early life trauma (figure A): 1) Early Post-natal trauma during Stage 1: Prior to the functional maturation of AMY, fear learning systems cannot be sufficiently activated. 2) Middle Post-natal trauma during Stage 2: After the functional maturation of the AMY, but prior to the maturation of hippocampal context processing pathways, associative fear responses cannot be established, yet non-associative sensitization of fear and neuroendocrine responses persist. 3) Late Post-natal trauma during Stage 3: With the maturation of both systems both appropriate conditional responses can be acquired as well as a sustained adult enhancement of amygdala-based fear learning. To test these hypothesize we propose to identify the functional status of the fear neural circuits to early life trauma and how this contributes to development of adult PTSD related symptomology. This will be accomplished by using a neuroanatomical approach in which we are capable of characterizing the expression of immediately early genes within the amygdala and its associated afferent and efferent brain regions in response to repeated footshock trauma during early (P8), middle (P19) and late (P35) post-natal development. Next we address the long-lasting impact of trauma at these developmental time points on adult fear and neuroendocrine function. By understanding the how the maturing brain is susceptible to early-life trauma, this could provide great insight into mechanisms underlying a debilitating anxiety disorders such as PTSD.

Public Health Relevance

Child abuse or early trauma is a major risk factor for the adult development of numerous health problems including post-traumatic stress disorder (PTSD). The strong relationship between childhood trauma and PTSD is of particular interest. This disabling disorder afflicts several million people around the world and has a prevalence rate of at least 8 % in the U.S. Our goal is to use an animal model to identify early developmental periods of greatest susceptibility and identify behavioral and brain markers of PTSD; which could provide future means of developing cognitive-behavioral and pharmacological treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
7R03MH093781-03
Application #
8792291
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Vicentic, Aleksandra
Project Start
2012-04-01
Project End
2015-03-31
Budget Start
2014-01-21
Budget End
2015-03-31
Support Year
Fiscal Year
2014
Total Cost
$54,861
Indirect Cost
$19,004
Name
State University of New York at Albany
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
152652822
City
Albany
State
NY
Country
United States
Zip Code
12222