THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OF AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEAD ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE APPLICATION BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. Although trauma can have profound psychological and physiological effects on the developing child, there have been no double-blind placebo- controlled pharmacologic trials for the treatment of posttraumatic stress disorder in children. The present proposal is a double-blind, placebo- controlled trial of clonidine for the treatment of PTSD in children. Clonidine is an alpha2-adrenergic agonist that acts by decreasing noradrenergic transmission. Numerous preclinical and clinical descriptive, psychophysiologic, neuroendocrine and pharmacologic challenge studies point to an increased responsivity of the sympathetic nervous system that is detectable under conditions of """"""""stress"""""""" in adults and children with PTSD. Increased sensitivity of the noradrenergic system appears to leave the individual in a hyperaroused, vigilant, sleep- deprived and at times agitated state that may worsen over time. It is hypothesized that traumatized children treated with clonidine will have a greater reduction in PTSD symptoms than children treated with placebo. Further, it is hypothesized that baseline pre-treatment levels of catecholamines, acoustic startle and cardiovascular measurements will be significantly correlated with treatment outcome. Finally, it is predicted that decreases in catecholamine activity over time will be associated with decreased PTSD symptomatology, acoustic startle and cardiovascular measures. These hypotheses will be tested in a trial of 30 traumatized children with PTSD in each of the two treatment groups (active and placebo). It is hoped that early pharmacologic intervention in children with PTSD will help to prevent the long-term consequences of disordered arousal.
