Early life stress, such as child maltreatment, is a major health concern in the United States due to both adverse physical and psychological consequences. Maltreatment not only results in physical harm to the victim, but puts the victim at higher risk for developing many psychopathologies including anxiety disorders, depression, conduct disorders, social incompetence and cognitive dysfunction. These outcomes are thought to be neurodevelopmental in nature, a consequence of repeated stress system activation in response to maltreatment experiences early in development. Prospective, longitudinal studies are necessary to address this hypothesis. Thus the goal of this proposal is to longitudinally examine the neurodevelopmental basis of psychopathologies associated with child maltreatment in a nonhuman primate model. This proposal will focus on the developmental alterations of prefrontal-amygdala circuits in a monkey model of maltreatment. Psychopathologies involving these circuits, such as fear, anxiety, behavioral inhibition and, in general, emotional regulation disorders are observed in victims of maltreatment. Evidence from cross-sectional studies does show alterations in these regions associated with maltreatment;however it is unknown whether altered development of these circuits underlies the alterations in associated behaviors and psychopathologies. Understanding how altered development of these circuits results in psychopathology would not only lead to treatment development, but also contribute to the identification of critical developmental periods for treatment, and possibly prevention, of adverse outcomes.
Aim 1 will examine the development of prefrontal-amygdala circuits using cutting-edge longitudinal neuroimaging techniques (structural MRI and diffusion tensor imaging - DTI-) and Aim 2 will investigate development of emotional behavior using a sensitive laboratory task. The data collected in these two aims will be examined for relationships between brain and behavior throughout early development in a nonhuman primate model of infant maltreatment. During the proposed research I will have the opportunity to learn state-of-the-art longitudinal neuroimaging, development of the primate brain and behavior and translational neuroscience from two researchers with strong experience in these domains. With the guidance of Drs. Sanchez and Bachevalier at the Yerkes National Primate Research Center (Emory Univ), as well as through our close collaboration with Dr. Martin Styner (UNC- Chapel Hill), I will have a unique opportunity to develop my strong potential and scientific passion into a productive and independent research career in developmental behavioral neuroscience with a focus on in vivo neuroimaging. The type of translational developmental work being conducted at Yerkes using socially housed nonhuman primates, and the strong collaborations of Drs. Sanchez and Bachevalier with child development researchers is absolutely unique, making this the ideal arena for me to jumpstart my long-term career goals.
The proposed studies will significantly impact our understanding of the developmental time course of maltreatment-associated alterations in the brain and how these alterations are related to behavioral alterations, providing both basic researchers and clinicians with critical information of the neurobiological mechanisms by which early life stress leads to such long-lasting debilitating consequences. The use of a unique nonhuman primate animal model of infant maltreatment and a prospective, longitudinal design will allow us to answer critical questions that are extremely difficult to address in human studies, informing the development of more efficacious prevention, intervention and treatment strategies for at risk human populations. The proposed research will also provide crucial longitudinal imaging data on normative brain development of socially housed macaques, greatly benefiting other research groups trying to understand the role of neurodevelopment in other conditions.
|Howell, Brittany R; Sanchez, Mar M (2011) Understanding behavioral effects of early life stress using the reactive scope and allostatic load models. Dev Psychopathol 23:1001-16|