Abstract: Early life adversity (e.g., maltreatment, neglect, divorce, poverty, chronic illness, etc), whether in rodents, non-human primates, or humans, frequently impacts development and function of multiple systems across the life span. The severity and direction (i.e., negative or positive) of these effects is sensitive to numerous factors encompassing gender, developmental age, sensitive periods, gene polymorphisms, level of social support, and social context. Responding to these insults activates allostatic processes by which the organism actively attempts to reregulate key physiological systems to maintain stable functioning within a biologically appropriate dynamic range. In humans, early life adversity initiates the following cascade: (1) increases the physiological reaction to stress; (2) increases the degree to which one perceives events as stressful in ambiguous situations; (3) poorer stress coping skills due to reduced emotional control and worse social skills. The cumulative cost, or allostatic load, of this process may lead to serious pathophysiology. Depending upon environmental and other factors, the end result can extend from changes in regional gene methylation, structural changes in the brain, increased vulnerability to sympathetic nervous system and hypothalamic-pituitary-adrenal axis (HPA) hyper-reactivity, immune system dysfunction, metabolic and cardiovascular diseases, learning and memory deficits, to psychiatric disease. Alternatively, in the presence of certain gene polymorphisms that increase sensitivity to the environment and solid social support, early life adversity gives rise to an apparent resilience. While researchers have yet to establish why and how early adversity has such profound and long-lasting effects, any model attempting to predict and explain these observations must encompass molecular, biological, and social-cultural factors.
Bio: Paul M. Plotsky is Director of the Stress Neurobiology Laboratory and is the GSK Professor of Psychiatry. His research is focused on the interaction between genes and the perinatal environment in shaping the developing nervous system. Using rodent and nonhuman primate models in collaboration with clinical researchers, he has developed animal models of vulnerability to a variety of psychiatric and medical diseases. Extensive characterization of these models ranging from behavioral assessments to gene expression and epigenetic profiling, as well as neuromorphology have revealed fundamental changes in neurocircuits underlying perception and processing of environmental stimuli as well as the responsiveness to these events. These models permit a detailed analysis of behavioral, neuroendocrine, cognitive, structural, neurochemical, and molecular changes associated with these vulnerable states and provide avenues for development of new therapeutic interventions. Dr. Plotsky holds adjunct appointments in the Dept. of Psychology and at the Yerkes National Primate Research Center. He is also on the faculty of the Graduate Program in Neuroscience and the undergraduate Neurobiology and Behavior Program.