PET mapping of 5HT receptor in major depression/suicide

项目3将使用PET神经受体成像技术测试该中心的中心主题之一，即大脑关键区域中5-羟色胺（5-HT）传输的改变赋予自杀企图的脆弱性。我们小组的尸检研究表明，杏仁核和眶额皮质腹外侧部分的5-HT转运蛋白（SERT）减少和5-HT 1A受体密度增加可能与自杀的易感性有关。这一结果与杏仁核和眶额皮质分别在攻击性和冲动性调节中的作用是一致的。这些假设将在五年内通过研究三组受试者中[11 C]McN 5652和[11 C]WAY 100635的SERT和5-HT/1A受体的体内分布进行检验。第1组将包括患有重度抑郁症和有严重自杀企图史的患者。第2组将包括患有重度抑郁症但没有任何自杀企图史的受试者。第3组将包括健康对照。每组将包括30名受试者，研究时间超过5年。各组将在年龄、性别、种族、社会经济背景和尼古丁吸烟方面进行匹配。此外，第1组和第2组的抑郁严重程度将匹配（就当前发作和既往抑郁史而言）。与重性抑郁症易感性相关的改变预计在第1组和第2组中均会发现，而与自杀易感性相关的改变预计仅在第1组中发现。因此，本设计将测试该中心的一个中心假设，即5-HT功能的改变赋予自杀企图本身的脆弱性，超过5-HT功能的改变是自杀企图本身的脆弱性的基础，超过5-HT功能的改变是抑郁症的脆弱性的基础。类似的假设也将在项目4C中研究的一组精神分裂症受试者中进行检验。因此，将比较有和无自杀企图史的精神分裂症患者，以检测本研究中检测到的与自杀易感性相关的神经化学异常（抑郁受试者）是否也存在于另一个与高自杀风险相关的诊断组中。

Project 3 will test with PET neuroreceptor imaging techniques one of the central theme of this center, i.e. that alterations in serotonin (5-HT) transmission in key brain regions confers vulnerability to suicidal attempts. Postmortem studies from our group suggest that decreased 5-HT transporters (SERT) and increased 5-HT1A receptor densities in the amygdala and the ventro-lateral portion of the orbitofrontal cortex might be associated with a vulnerability to suicide. The results are consistent with the role of the amygdala and the orbitofrontal cortex in the modulation of aggressivity and impulsivity, respectively. These hypotheses will be tested over five years by studying in vivo the distribution of SERT with [11C]McN 5652 and 5-HT/1A receptors with [11C]WAY 100635 in three groups of subjects. Group 1 will include patients with major depression and a history of a severe suicide attempt. Group 2 will include subjects with major depression, but without any history of suicide attempts. Group 3 will include healthy controls. Each group will include 30 subjects studied over 5 years. Groups will be matched on age, gender, race, socioeconomic background and nicotine smoking. In addition, groups 1 and 2 will be matched for severity of depression (both in terms of the current episode, and in terms of previous history of depression). Alterations associated with vulnerability to major depression are expected to be found in both groups 1 and 2, while alterations associated with suicide vulnerability are expected to be found only in group 1. Thus, this design will test one of the central hypotheses of this Center, i.e. that alterations of 5-HT function confer a vulnerability to suicide attempts per se, over and above alterations of 5-HT function that underlie vulnerability to suicide attempts per se, over and above alterations of 5-HT function that underlie vulnerability to major depression. A similar hypotheses will also be tested in a group of schizophrenic subjects studied in project 4C. Thus, patients with schizophrenia with and without a history of suicidal attempts will be compared, to test if neurochemical abnormalities associated with vulnerability to suicide detected in this study (depressed subjects) are also present in another diagnosis group associated with high suicidal risk.