The general objectives of this application (ADAMHA, RSDA, Level II) are to evaluate serotonin (5-HT) activity in aggressive conduct-disordered children. This will be accomplished by diagnostically identifying 3 groups ('aggressive conduct disorder,' 'other diagnoses,' 'normals'), employing well-standardized instruments to measure (1) aggression, (ii) impulsivity, (iii) factors of psychopathology and (iv) biochemical methods for markers of serotonergic activity in blood elements.
Some specific aims are: (1) To investigate whether aggressive conduct-disordered children demonstrate abnormalities in platelet markers of serotonergic function associated with presynaptic or postsynaptic activity, (2) To relate the platelet 5-HT data to experimental paradigms/rating scale/test batteries which quantify (a) different types of aggressive responses, (b) variables of impulsivity, (c) factors of psychopathology, (d) observations of prosocial behavior, (e) neurological soft signs and (f) cognitive functioning, (3) To determine if developmental differences exist in platelet markers of serotonergic activity in aggressive and normal children, (4) To determine if there is a correlation between platelet and central serotonergic activity in animals and humans, (5) To extend the studies on platelet markers of 5-HT biochemistry to adolescent aggression/suicide (adding measurement of CSF monoamine metabolites) and to a double blind lithium trial of aggressive conduct disorder. These studies will shed light on the role of 5HT as a contributing factor to some types of aggressive behavior, which are also probably influenced by genetic and psychosocial factors. Measurements of platelet biochemical markers of serotonergic activity should permit cogent theorizing about specific aspects of 5-HT physiology involved in the aggression of children, suggesting drug trials and/or dietary manipulations by treatments influencing serotonergic neurotransmission. Professional growth and research development involves acquisition of knowledge and skill in """"""""state of the art"""""""" clinical, quantitative, analytic methods and concepts. This includes construction and standardization of better measures of aggression and response disinhibition in children, diagnostic issues separating out the components of Externalizing behavior disorders, receptor methodology and other analytical techniques for characterizing novel 5-HT related binding sites and its second messenger transducing system in platelets. It is anticipated that this award could provide the support for development of a research career, dedicated towards obtaining a better understanding of the biological roots of disturbed human behavior, enabling the opportunity to make significant contributions to the biochemistry of aggression and other impulse related problems in children and adolescents.
