Identification of Neurobiological Intermediate Phenotypes in Major Depressive Dis

描述(由申请人提供)：NIMH的一个主要倡议是早期识别精神障碍的风险中间表型(IP)，以及这些IP随着发作的复发而进展。对疾病活跃状态的长期关注，而不是对缓解状态的关注，阻碍了对这些IP及其随时间的稳定性的准确研究。本研究旨在通过招募青春期晚期/成年期早期病程早期的MDD患者来更好地识别神经生物学IP。我们将在三周内建立IP的稳定性，然后对这些人进行为期一年的跟踪，以使用这些IP来预测抑郁症的复发。我们小组和其他人的研究表明，抑郁症和焦虑症(MDD+A)共病是MDD的一个强健亚型。这支持了之前的研究，即先前存在的焦虑症增加了患MDD的风险，治疗反应较差的风险，以及更大的复发机会。因此，更好地了解这些年轻人的健康益处具有巨大的潜力，可以启动更有针对性的治疗策略，并确定那些最需要后续行动的人。年龄在18岁到22岁之间的MDD缓解期的61名年轻成年人以及60名年龄和性别相匹配的健康对照将被纳入研究。MDD受试者要么从有阳性家族史的第一集开始缓解，要么在没有家族史的第二和第三集之间缓解。70名MDD受试者将被平均分配给有和没有焦虑症病史的人，并与60名健康对照年轻人进行比较。神经生物学IP测量包括情绪、调节(抑制控制)和记忆范式以及类似的神经心理学测量(记忆、情绪处理、执行功能)的功能磁共振成像。这些措施将在指标点(缓解状态)使用，并在3周后再次使用(以评估性状稳定性)。分析的重点将集中在1)确定MDD+A与MDD IP的特征，2)这些IP在缓解状态下的稳定性，以及3)这些IP预测一年后抑郁症复发/复发的能力。我们将在关键节点对这些个体进行研究，在疾病的早期，与对更年轻青少年的研究相比，那里的发育变异性将被最小化。这将使我们能够在累积疾病影响出现之前评估这些IP的存在和稳定性。将对神经生物学IP的搜索嵌入到复发预测研究中，可以随时将发现转化为临床环境。纵向方法巩固了诊断，解决了IP措施的稳定性，并提供了一个进入临床应用的简单入口，如果我们来自异质MDD组的初步结果在这些更均匀的样本中重复的话。大脑机制允许这位PI进行这一创新的关键冒险，以完善他在患有MDD+A和MDD的成年人IP方面的初步工作。 公共卫生相关性：及早识别有抑郁风险的人可以导致预防性和/或早期治疗，但MDD的中间表型在青春期后期/成年期早期尚未得到很好的研究。这项研究将使用神经生物学方法鉴定MDD伴和不伴焦虑的稳定的内表型，这可能导致早期识别MDD的危险人群，并促进MDD的危险基因的追寻。

DESCRIPTION (provided by applicant): A major initiative of NIMH is the early identification of risk intermediate phenotypes (IPs) for psychiatric disorders and the progression of these IPs with recurrence of episodes. The longtime focus on active disease states, rather than the remitted state, has thwarted precise study of these IPs and their stability over time. The present study is designed to better identify neurobiological IPs by enrolling individuals remitted from MDD, early in the course of illness in late adolescence/early adulthood. We will establish the stability of IPs over a three week period, and then follow these individuals for 1 year to use these IPs to predict recurrence of depressive illnesses. Research by our group and others suggests that comorbid depression and anxiety (MDD+A) is a robust subtype for MDD. This supports the previous research that pre-existing anxiety disorder increases risk for MDD, risk for poorer treatment response, and greater chance of relapse. As such, the health benefits of better understanding these young adults has great potential to initiate more tailored treatment strategies, and to identify those most in need of follow-up. Sixty first episode young adults between the ages of 18 and 22 remitted from MDD will be enrolled in the study as well as sixty age and sex matched healthy controls. The MDD subjects will be either remitted from a first episode with positive family history, or between the second and third episodes with no family history. The 70 MDD subjects will be evenly divided between those with and without a prior history of anxiety disorder and compared to 60 healthy control young adults. Neurobiological IP measures include fMRI with emotion, regulation (inhibitory control), and memory paradigms and similar neuropsychological measures (memory, emotion processing, executive functioning). These measures will be used at the index point (remitted state) and again 3 weeks later (to assess trait stability). Analyses will focus on 1) defining the trait MDD+A vs trait MDD IPs, 2) stability of these IPs in the remitted state, and 3) ability of these IPs to predict relapse/recurrence of depressive illness at one year. We will study these individuals at the critical nexus, early in the course of illness where developmental variability will be minimized compared to studies of younger adolescents. This will enable us to assess the presence and stability of these IPs before cumulative illness effects are present. Embedding the search for neurobiological IPs into a relapse prediction study can provide for ready translation of findings into clinical settings. A longitudinal approach solidifies diagnoses, and addresses stability of IP measures, and provides a easy entrie into a clinical application, should our preliminary results from a heterogeneous MDD group be replicated in these more homogeneous samples. The BRAINS mechanism allows this PI to take this innovative, critical venture toward refining his initial work on IPs for adults with MDD+A and MDD. PUBLIC HEALTH RELEVANCE: The early identification of those with risk for depression can result in preventative and/or early treatments, yet intermediate phenotypes of MDD have not been well studied in late adolescence/early adulthood. The present study will identify stable endophenotypes for MDD with and without comorbid anxiety using neurobiological measures that could lead to early identification of those at risk for MDD and facilitate pursuit of risk genes for MDD.