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，即关键大脑区域5-羟色胺(5-HT)传递的变化使自杀企图变得脆弱。我们小组的尸检研究表明，杏仁核和眶前叶皮质腹外侧部5-羟色胺转运体(SERT)减少和5-HT1a受体密度增加可能与自杀易感性有关。结果与杏仁核和眶前叶皮质分别在调节攻击性和冲动性中的作用是一致的。这些假说将通过体内研究[11C]MCN5652和5-HT/1A受体的SERT在三组受试者中的分布([11C]方法100635)来验证。第一组将包括有严重抑郁症和严重自杀未遂病史的患者。第二组将包括患有严重抑郁症但没有任何自杀未遂病史的受试者。第三组将包括健康对照组。每组将包括30名研究对象，研究时间为5年。这些群体将在年龄、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(根据当前发病情况和以前的抑郁症病史)。预计在第1组和第2组中都会发现与重度抑郁症易感性相关的改变，而与自杀易感性相关的改变预计只会在第1组中发现。因此，这项设计将检验该中心的核心假设之一，即5-羟色胺功能的改变本身对自杀企图本身具有易感性，而5-羟色胺功能的改变本身是导致自杀企图的易感性的基础，而5-羟色胺功能的改变是导致重度抑郁症易感性的基础。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测试。因此，有和没有自杀未遂病史的精神分裂症患者将被比较，以测试在这项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)是否也存在于另一组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.