Disturbances in brain serotonin (5-HT) metabolism have been implicated in the pathogenesis of affective disorders. The objectives of this proposal are to test the hypothesis that suicide victims have increased numbers of serotonin receptors in frontal cortex, and that previous psychiatric history of major depression, violence or impulsive behavior is correlated with receptor binding.
The specific aims of this research are: 1) to extend the finding of elevated serotonin 2 (5-HT[2]) receptor binding in homogenates of frontal cortex of violent suicides as compared with nonviolent suicides and matched controls by using in vitro quantitative autoradiography to anatomically localize and quantitate receptor binding. 2. To use in vitro quantitative autoradiography to extend the finding of elevated 5-HT 1A receptor binding in homogenates of frontal cortex of nonviolent suicides as compared with matched controls. 3. To compile a psychological history of the suicide completers used in the receptor binding experiments to determine if previous psychiatric diagnoses are correlated with altered receptor binding. 4. To determine with in vitro quantitative autoradiography whether the high-affinity binding of {3H}paroxetine to the 5-HT transporter complex in sections of frontal cortex of violent and nonviolent suicide completers is different from that in matched controls and if it correlates with 5-HT, and/or 5-HT 1A receptor binding. 5. To study the role of serotonin and dopamine in frontal cortex of suicide completers and matched controls by measuring concentrations of serotonin, dopamine, 5-hydroxyindoleacetic acid, and, homovanillic acid. The studies proposed here to combine psychiatric histories collected from structured interviews with next-of-kin using the SADS-L and SIDP assessment instruments together with quantitative in vitro receptor autoradiography should provide a significant improvement over previous attempts to test the hypothesis that serotonin receptor dysfunction is linked with violence, suicide and/or depression. These studies could provide important preliminary steps toward the eventual goal of imaging monoamine receptors in vivo in patients suffering from depression.
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