Despite the wealth of data supporting the hypothesis that central pre- synaptic serotonin (5-HT) function is reduced in male patients with suicidal and/or impulsive aggressive behaviors, little is conclusively known concerning the relationship between these behaviors and indices of post-synaptic or overall (""""""""integrated"""""""" or """"""""net"""""""") 5-HT function. Moreover, since little is known regarding the relationships among different putative indices of 5-HT function, our understanding of how to best interpret these data is limited. Finally, since few studies of central 5-HT activity and impulsive aggressive behavior in female subjects have been performed, little is known regarding these issues in women and the possibility of a gender difference in these relationships remains to be tested. In order to address these issues we propose to conduct three parallel studies which assess the relationship between central 5-HT function and suicidal and impulsive aggressive behavior in a psychiatric and in a normal control population. We propose to examine three indices of central 5-HT function in male and female patients with DSM-III-R personality disorder (PD) and in age and sex matched normal controls. These indices include: a) lumbar CSF concentrations of 5-HIAA as an index of """"""""pre-synaptic"""""""" 5-HT activity; b) PRL responses to the direct post-synaptic 5-HT agonist m- chlorophenylpiperazine (m-CPP) as an index of """"""""post-synaptic"""""""" receptor function; and c) PRL responses to the 5-HT releasing/uptake-inhibiting agent d-fenfluramine (d-FEN) as an index of integrated """"""""pre-/post-synaptic"""""""" function). We have chosen to study personality disorder patients as the experimental group because suicidal and impulsive aggressive behaviors exist across a wide continuum in this group and because of previous data which indicate that PD patients consistently demonstrate inverse relationships between indices of central 5-HT function and both suicidal and impulsive aggressive behavior. Based upon previous work, we hypothesize that: a) the proposed indices of central 5-HT function will be intercorrelated; b) CSF 5-HIAA concentrations (5-HT """"""""pre-synaptic"""""""") and PRL responses to both m-CPP (5-HT """"""""post- synaptic"""""""") and d-FEN (5-HT """"""""integrated pre-/post-synaptic"""""""") will be inversely related to suicidal and impulsive aggressive in behaviors in both male and female PD patients; and c) relationships between the PRL response to d-FEN, as an index of """"""""integrated pre-/post-synaptic"""""""" index of 5-HT function, and those observed between the above behavioral variables will be stronger than those observed with either CSF 5-HIAA 95-HT """"""""pre-synaptic"""""""") or the PRL response to m-CPP (""""""""post-synaptic"""""""").
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