Fronto-Limbic Brain of Bipolar Children and Adolescents

双相情感障碍儿童和青少年的额叶边缘脑

• 批准号: 6924337
• 负责人: JAIR C SOARES
• 金额: $ 50.45万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-02 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6924337
• 关键词: adolescence (12-20); amygdala; anxiety disorders; aspartate; attention deficit disorder; behavioral /social science research tag; bipolar depression; brain morphology; cingulate gyrus; clinical research; clinical trials; comorbidity; corpus callosums; executive function; frontal lobe /cortex; gray matter; human subject; human therapy evaluation; limbic system; longitudinal human study; magnetic resonance imaging; mental disorder chemotherapy; neuropathology; neuropharmacology; neuropsychological tests; neuropsychology; oppositional defiant disorder; patient oriented research; prefrontal lobe /cortex; psychopathology; valproate

Abnormalities in fronto-limbic brain (FLB) regions involved in mood regulation have been associated with bipolar disorder (BD) in neuroimaging studies on adults. Did these FLB changes develop as BD progressed, or did they emerge early during BD development? The latter would suggest that (1) developmental abnormalities in brain maturation processes may have led to these FLB changes. And, if so, then (2) treatments that reduced or alleviated these brain changes early in the disease process might reduce the severity of BD. To test these hypotheses, we will conduct a combined in vivo neuroimaging and clinical intervention trial in post-pubertal adolescents (ages 12-17 years old) who have BD (BD adolescents), that will examine the relationships between (a) FLB abnormalities, (b) BD progression and severity, and (c) response to a mood-stabilizing medication (valproate). We will study 60 untreated BD adolescents and 60 matched healthy controls. 30 BD patients will not have comorbid attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), and/or conduct disorder (CD), while another 30 will have these comorbid conditions. Patients in both groups may also have comorbid anxiety disorders, with the exception of obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). The 60 patients will enter a 6-week open trial with valproate at therapeutic doses (as measured by serum valproate levels). Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) will be performed to compare brain anatomy (size of key FLB regions involved in mood regulation, with a focus on prefrontal cortex and amygdala) and neurochemistry (levels of N-acetyl aspartate (NAA), a non-specific marker of neuronal viability or function) across the 3 groups, as well as after treatment. Neuropsychological testing will also be conducted to evaluate specific FLB functions. This will be the first in vivo evaluation of FLB abnormalities in BD adolescents and in their response to treatment. It will contribute to elucidating the pathophysiologic mechanisms of BD, to understanding the mechanisms of action of mood stabilizers, and to identifying new endophenotypes of BD or biological targets that could aid in diagnosis, monitoring or treatment.

在成人神经影像学研究中，涉及情绪调节的额叶边缘大脑（FLB）区域的异常与双相情感障碍（BD）有关。这些 FLB 变化是随着 BD 的进展而发生的，还是在 BD 发展的早期就出现了？后者表明 (1) 大脑成熟过程中的发育异常可能导致了这些 FLB 变化。如果是这样，那么 (2) 在疾病过程早期减少或减轻这些大脑变化的治疗可能会减轻双相情感障碍的严重程度。为了检验这些假设，我们将对患有 BD 的青春期后青少年（12-17 岁）（BD 青少年）进行体内神经影像学和临床干预联合试验，该试验将检查 (a) FLB 异常、 (b) BD 进展和严重程度，以及 (c) 对情绪稳定药物（丙戊酸盐）的反应。我们将研究 60 例未经治疗的 BD 青少年和 60 名匹配的健康对照者。 30 名 BD 患者不会患有注意力缺陷多动障碍 (ADHD)、对立违抗性障碍 (ODD) 和/或品行障碍 (CD)，而另外 30 名患者则患有这些共病。除强迫症（OCD）和创伤后应激障碍（PTSD）外，两组患者都可能患有焦虑症。这 60 名患者将进入为期 6 周的开放试验，使用治疗剂量的丙戊酸（通过血清丙戊酸水平测量）。将进行磁共振成像 (MRI) 和磁共振波谱 (MRS) 来比较大脑解剖结构（参与情绪调节的关键 FLB 区域的大小，重点是前额皮质和杏仁核）和神经化学（N-乙酰天冬氨酸水平） NAA），神经元活力或功能的非特异性标志物）在三组中以及治疗后。还将进行神经心理学测试来评估特定的 FLB 功能。这将是首次对 BD 青少年 FLB 异常及其对治疗的反应进行体内评估。它将有助于阐明双相情感障碍的病理生理机制，了解情绪稳定剂的作用机制，并确定双相情感障碍的新内表型或有助于诊断、监测或治疗的生物学靶点。