Dysfunctional Cortico-Limbic Activity and Connectivity in Bipolar Disorder and Li

描述（由申请人提供）：该竞争性修订旨在扩大当前R 01-“双相情感障碍中的皮质边缘活动和连接功能障碍”的范围，以在基线时研究20名处于正常胸腺状态（BDE）的双相情感障碍（BD）患者和40名BD患者的未受影响同胞（UAS），并响应通知编号（NOT-OD- 09-058），标题为：“NIH宣布恢复法案资金用于竞争性修订申请”。父母资助计划同时测量40名未用药的BD躁狂期（BDM）患者和40名抑郁期（BDD）患者在锂治疗前后以及40名匹配的健康对照受试者的皮质杏仁核连接以及区域边缘系统激活。先验定义的感兴趣区域是皮质情绪调节区域-腹侧前扣带皮质（vACC）和杏仁核。第一个目的是使用一种新的连接特异性测量-静息状态低频BOLD波动（LFBF）相关性来测量皮质杏仁核连接。第二个目的是使用主动面部情绪识别任务来测量杏仁核激活。初步数据分析揭示了有趣的结果，表明与健康受试者相比，BD患者的杏仁核激活增加，皮质杏仁核连接减少，并且这种异常在BDD和BDM患者中均存在。此外，有一级亲属心境障碍家族史的BD患者比无家族史的患者皮质杏仁核连通性下降更大。这些结果表明，皮质杏仁核连接和杏仁核激活的反应，面对任务可以作为内表型，以探讨遗传病因的BD。然而，为了进一步加强这些发现，我们还需要研究BDE患者和BD患者的UAS。在进行母研究的同时，我们筛选了一些此类受试者，由于没有资金，我们目前无法进行研究。因此，正在申请该竞争性修订，以要求适量的补充，以研究BD患者BDE和UAS的基线皮质杏仁核激活和连接异常。纳入这两组将补充母研究的总体目标-研究可能是BD遗传和神经生物学病因所固有的回路水平皮质杏仁核异常。 公共卫生相关性：这是对母基金的竞争性修订-“双相情感障碍中的功能障碍性皮质边缘活动和连接性以及锂的影响”，正在研究40名躁狂症，40名双相抑郁症和40名健康受试者，正在提交以扩大母基金的范围，以研究20名心境正常的双相情感障碍患者和40名双相情感障碍患者的未受影响的兄弟姐妹。这项研究将补充父母补助金，旨在阐明双相情感障碍的遗传和神经生物学病因。

DESCRIPTION (provided by applicant): This competitive revision is to enlarge the scope of the current R01 - 'Dysfunctional Corticolimbic Activity and Connectivity in Bipolar Disorder' to also study at baseline 20 bipolar disorder (BD) patients in the euthymic state (BDE) and 40 unaffected siblings (UAS) of BD patients, and is in response to Notice Number (NOT-OD- 09-058), titled: "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". The parent grant proposes to concurrently measure both corticoamygdalar connectivity as well as regional limbic activation in 40 unmedicated BD patients in manic phase (BDM) and 40 in the depressed phase (BDD) before and after treatment with lithium as well as 40 matched healthy control subjects. The a priori defined regions of interest are the cortical mood regulating region - ventral anterior cingulate cortex (vACC) and the amygdala. The first aim is to measure corticoamygdalar connectivity using a novel connectivity specific measure - resting state low frequency BOLD fluctuations (LFBF) correlations. The second aim is to measure amygdalar activation using an active facial emotion recognition task. Preliminary data analysis has revealed interesting results which suggest that amygdalar activation is increased and corticoamygdalar connectivity is decreased in BD compared to healthy subjects and this abnormality is state independent being present in both BDD and BDM patients. Furthermore, BD patients with a family history of mood disorder in a first degree relative have a greater decrease in corticoamygdalar connectivity than the ones without a family history. These findings suggest that corticoamygdalar connectivity and amygdalar activation in response to face task could be used as endophenotypes to investigate the genetic etiology of BD. However, to further strengthen these findings we also need to study BDE patients and UAS of BD patients. While conducting the parent study, we have screened a number of such subjects who we cannot study at this time as funding is not available. Therefore, this competing revision is being applied for to ask for a modest amount of supplement to investigate baseline corticoamygdalar activation and connectivity abnormalities in BDE and UAS of BD patients. Inclusion of these two groups will complement the overall aim of the parent study - investigating the circuit level corticoamygdalar abnormalities which may be inherent to the genetic and neurobiological etiology of BD. PUBLIC HEALTH RELEVANCE: This competing revision of the parent grant - 'Dysfunctional Corticolimbic Activity and Connectivity in Bipolar Disorder and Effect of Lithium' which is studying 40 manic, 40 bipolar depressed and 40 healthy subjects is being submitted to enlarge the scope of the parent grant to also study 20 euthymic bipolar patients and 40 unaffected siblings of bipolar patients. This study will complement the parent grant aims to elucidate the genetic and neurobiological etiology of bipolar disorder.