Neurotransmitter Imaging in Vivo in Mood Disorders and Suicidal Behavior

项目3研究了患有MDD的自杀者的死后神经递质发现和放射配基的发展 最后五年，并以一种最好的体内正电子发射的方式将它们聚集在一起 断层扫描(PET)。我们和其他人发现5-羟色胺能系统异常，主要是5-羟色胺 抑郁症自杀者死后IA受体(5-HTIA)和5-羟色胺转运体(5-HTT)我们有飞行员 PET数据显示MDD自杀未遂者与自杀者相同脑区的5-HTT低结合 与MDD非精神分裂症患者和健康志愿者比较。这表明可能与自杀有关 在首次自杀未遂之前，可能在MDD中检测到的自杀者的生物内表型。在这 我们试图确定这是否是第一次自杀之前存在的一种内表型 MDD的企图或发病及其与童年逆境的关系。我们发现5-HTT结合是 在有童年逆境报告的抑郁症患者中较低。啮齿动物研究表明，早期的逆境 改变5-HTIA结合。具体地说，我们假设[11C]DASB 5-HTT结合在MDD中将是低的 试探者和童年的逆境将促成这一效果。使用我们新的激动剂5-HTIA放射性示踪剂， [11C]CUMI-101，我们预测MDD患者的5-HTIA激动剂结合率较高，如自杀患者。我们 MDD自杀未遂者中5-HTIA和5-HTT结合的假设，与MDD比较 非未遂者和控制者在自杀中的发现是相似的。这两种PET示踪剂将用于相同的 确定哪种示踪剂最能检测到组之间的差异，并将这些数据 奥格登博士在P6中使用的。为了确定这是否是潜在的内表型，我们将扫描一组高危人群 MDD未遂者的后代在他们第一次自杀未遂或MDD发作之前。在过去的两年里 我们将研究新的神经递质靶点，以扩大我们关于自杀行为的知识库。 我们将测定健康志愿者和MDD自杀未遂者的单胺氧化酶A(MAOA)水平。 MAOA在MDD中表达上调，与突触5-羟色胺、DA和NE的降解有关。在 与MAOA相同的患者/对照组，我们将通过以下方式评估内源性阿片类神经递质系统 量化kappa阿片受体。我们将与其他核心和项目合作，研究 约束性措施、评估过程中的fMRI反应、应激反应、攻击性之间的关系 特征和报告的童年逆境的影响。

Project 3 takes postmortem neurotransmitter findings in suicides with MDD and radioligand development of the last five years and brings them together in a fashion that is best done with in vivo positron emission tomography (PET). We and others find abnormalities of the serotonergic system, principally the serotonin IA receptor (5-HTIA ) and serotonin transporter (5-HTT) postmortem in depressed suicides. We have pilot PET data indicating that low 5-HTT binding in the same brain regions as suicides in MDD suicide attempters compared with MDD nonattempters and healthy volunteers. This indicates a potential suicide-related biological endophenotype in suicides that may be detectable in MDD before the first suicide attempt. In this project we seek to determine whether this is an endophenotype that is present before the first suicide attempt or onset of MDD, and its relationship to childhood adversity. We have found that 5-HTT binding is lower in depressed patients with reported childhood adversity. Rodent studies indicate that early adversity alters 5-HTIA binding. Specifically, we hypothesize that [11C]DASB 5-HTT binding will be low in MDD attempters and childhood adversity will contribute to this effect. With our new agonist 5-HTIA radiotracer, [11C]CUMI-101, we predict higher 5-HTIA agonist binding in MDD attempters as seen in suicides. We hypothesize that the 5-HTIA and 5-HTT binding in MDD suicide attempters, compared with MDD nonattempters and controls, will parallel findings in suicides. Both PET tracers will be used in the same groups to determine which tracer is best to detect differences between the groups, and these data will be used by Dr. Ogden in P6. To determine if this is a potential endophenotype, we will scan a group of high-risk offspring of MDD attempters before their first suicide attempt or episode of MDD. In the last two years of the project we will study new neurotransmitter targets to expand our knowledge base about suicidal behavior. We will determine monoamine oxidase A (MAOA) levels in healthy volunteers and MDD suicide attempters. MAOA is upregulated in MDD and responsible for the degradation of synaptic serotonin, DA and NE. In the same patients/controls as for MAOA, we will evaluate the endogenous opioid neurotransmitter system, by quantifying the kappa opiod receptor. In collaboration with other Cores and Projects, we will examine the relationship between the binding measures, fMRI responses during appraisal, stress responses, aggressive traits and the effects of reported childhood adversity.