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

描述（由申请人提供）：此竞争性修订是为了扩大当前R01的范围-“双相情感障碍的功能失调皮质边缘活动和连通性”，以研究基线20名处于健康状态（BDE）的双相情感障碍（BD）患者和40名未受影响的兄弟姐妹（UAS）的BD患者，并响应通知号（NOT-OD- 09-058），标题为：“NIH宣布竞争性修订申请的恢复法案资金可用性”。父母资助计划同时测量40名未服药的躁狂期（BDM）和抑郁期（BDD）的BD患者在锂治疗前后以及40名匹配的健康对照者的皮质杏仁核连通性和区域边缘激活。先验定义的感兴趣的区域是皮质情绪调节区域-腹侧前扣带皮层（vACC）和杏仁核。第一个目标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的连通性。第二个目标是通过一个主动的面部情绪识别任务来测量杏仁核的激活。初步的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，皮质杏仁核连通性下降，这种异常在BDD和BDM患者中都是独立于状态的。此外，有一级亲属有情绪障碍家族史的双相障碍患者的皮质杏仁核连通性比没有家族史的患者下降得更大。这些发现表明，皮质杏仁核连通性和杏仁核对面部任务反应的激活可以作为研究BD遗传病因的内表型。然而，为了进一步加强这些发现，我们还需要对BDE患者和BD患者的UAS进行研究。在进行家长研究时，我们已经筛选了一些这样的受试者，由于资金不足，我们目前无法对他们进行研究。因此，这一竞争性修订正在申请适度补充，以研究BDE和UAS患者的基线皮质杏仁核激活和连通性异常。纳入这两组将补充母体研究的总体目标——研究电路水平的皮质扁桃体异常，这可能是双相障碍的遗传和神经生物学病因所固有的。

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.