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

双相情感障碍和 Li 中功能失调的皮质边缘活动和连接

• 批准号: 7839353
• 负责人: Amit Anand
• 金额: $ 26.95万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7839353
• 关键词: 7,7' -dimethoxy-(4,4' -bi-1,3-benzodioxole)-5,5' -dicarboxylic acid dimethyl ester; Aftercare; Amygdaloid structure; Anterior; Bipolar Disorder; Complement; Data Analyses; Disease; Emotions; Etiology; Face; Family history of; First Degree Relative; Frequencies; Funding; Genetic; Genetic Predisposition to Disease; Lithium; Manic; Measures; Mood Disorders; Moods; Neurobiology; Parents; Patients; Phase; Recovery; Rest; Role; Siblings; Stimulus; Time; United States National Institutes of Health; cingulate cortex; depressed; endophenotype; interest; novel; parent grant; public health relevance; response

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.

描述（由申请人提供）：这项竞争性修订是为了扩大当前R01-“双相情感障碍的可质性皮质临床活性和连通性”的范围，以便在基线20的双相情感障碍（BD）患者（BDE）（BDE）（BDE）（BDE）（BDE）和40名未发起的患者（UAS）（UAS）（UAS）（UAS）（UAS）（UAS）（UAS）（UAS）（uAS 5）的09-0-0-0-0-0-0-0-0-0-0-0-0-0-0。标题为：“ NIH宣布为竞争性修订申请提供恢复法案的可用性”。父母赠款提议同时测量40名未经药物的BD患者（BDM）（BDM）（BDD）和40名在lithium治疗之前和之后的抑郁阶段（BDD）中，同时测量40名未经药物BD患者的皮质型乳糖连通性以及区域边缘激活。先验定义的感兴趣区域是调节皮质情绪 - 腹侧扣带回皮层（VACC）和杏仁核。第一个目的是使用一种新型连通性指标 - 静止状态低频BOLD波动（LFBF）相关性测量皮质型乳糖连通性。第二个目的是使用主动面部情感识别任务来测量杏仁核激活。初步数据分析显示了有趣的结果，这表明与健康受试者相比，BD的杏仁核激活增加，皮质型乳腺素的连通性降低，并且这种异常在BDD和BDM患者中都是独立的。此外，与没有家族史的病史相比，具有一级相对的心情障碍家族病史的BD患者的皮质型乳糖连通性降低了。这些发现表明，响应面对任务的皮质型连通性和杏仁核激活可以用作研究BD的遗传病因的内表型。但是，为了进一步加强这些发现，我们还需要研究BD患者的BDE患者和UAS。在进行家长研究时，我们已经筛选了许多此类主题，因为这些学科目前无法研究，因为没有资金。因此，这种竞争性修订被用于要求提供适度的补充剂，以研究BDE和BD患者BDE和UAS的基线皮质型和连通性异常。包括这两组的包含将补充父母研究的总体目的 - 研究电路水平的皮质型和神经生物学病因可能固有的皮质型皮质型异常。 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.这项研究将补充父母的旨在阐明双相情感障碍的遗传和神经生物学病因。