Project 3: Neurobiological Characterization of Offspring of Biopolar Parents

尽管双相情感障碍的发病率和死亡率很高， 对这种疾病的发展基础知之甚少。青春期是最常见的 躁郁症的发作此外，双相父母的后代患双相情感障碍的风险更高 与一般人群相比，因此，一种澄清 双相情感障碍早期进展的神经发育基础模型和识别潜力 早期情绪发作的神经生物学预测因素是研究有风险的年轻受试者， 发展为双相情感障碍（即，有双相情感障碍的父母），但自己还没有情绪障碍。 双相情感障碍的特点是情绪和注意力的破坏。前边缘网络， 涉及腹侧前额叶皮层，丘脑，杏仁核和纹状体，似乎调节这些 流程.因此，我们假设双相情感障碍的症状源于功能障碍 在这个网络中。具体来说，功能成像（fMRI）研究表明，前边缘网络， 可能在双相患者中过度激活，从而产生这种病症的症状。 此外，磁共振波谱（MRS）研究表明，高代谢可能是 前边缘系统过度激活具体来说，MRS研究发现双相情感障碍患者表现出 与健康受试者相比，过量的谷氨酸（Glu）和肌醇（ml）浓度。 基于这些考虑，本研究的目的是：1）使用功能磁共振成像和1H MRS评估 双相情感障碍青少年和青年后代的功能和代谢前缘异常 采用fMRI和1HMRS技术评价大脑前边缘系统的功能和代谢 异常作为高危青少年和年轻人早期情绪障碍的潜在标志;以及 3)研究高危青少年和年轻人的前缘异常进展， 发展成情绪障碍为了实现这些目标，我们将获得神经代谢（MRS）和 神经功能（fMRI）测量140例受试者没有任何情绪障碍和双相父母 （风险，AR）和40名受试者没有一级亲属患有情绪障碍（健康，HC）， 建议进行纵向研究。双相情感障碍者和健康父母的后代之间的比较将定义 两组的基线fMRI和1H MRS异常和纵向随访将确定预测因子， 早期情绪发作的标志，以及神经发育变化是独特的， 双相情感障碍风险人群的情绪发作（中心目标1-3）。我们相信这 这些信息最终可以澄清双相情感障碍的神经生理学模型（中心目标1），并提供 神经生理学治疗目标，以防止双相情感障碍的发作，在那些有家族性 发展疾病的风险（中心目标2和3）。

Despite the significant morbidity and mortality associated with bipolar disorder, the neurophysiological basis of the development of this illness is poorly understood. Adolescence is the most common period of onset of bipolar disorder. Moreover, offspring of bipolar parents have an elevated risk of developing bipolar disorder compared with the general population. Therefore, one approach toward clarifying neurodeveloprriental models of the early progression of bipolar disorder and identifying potential neurobiological predictors of incipient mood episodes is to study young subjects who are at risk for developing bipolar disorder (i.e., have a bipolar parent), but do not yet have a mood disorder themselves. Bipolar disorder is characterized by disruption of mood and attention. The anterior limbic network, which involves the ventral prefrontal cortex, thalamus, amygdala, and striatum, appears to regulate these these processes. Consequently, we hypothesize that the symptoms of bipolar disorder arise from dysfunction within this network. Specifically, functional imaging (fMRI) studies suggest that the anterior limbic network may be excessively activated in bipolar patients, thereby producing the symptoms of this condition. Additionally, magnetic resonance spectroscopy (MRS) studies suggest that hypermetabolism may underlie the excessive anterior limbic activation. Specifically, MRS studies have found that bipolar patients exhibit excessive glutamate (Glu) and myoinositol (ml) concentrations compared with healthy subjects. With these consideration in mind, the goals of this study are: 1) To use fMRI and 1H MRS to assess functional and metabolic anterior limbic abnormalities in adolescent and young adult offspring of bipolar parents (at-risk); 2) To use fMRI and 1H MRS to evaluate functional and metabolic anterior limbic abnormalities as potential markers for incipient mood disorders in at-risk adolescents and young adults; and 3) To examine the progression of anterior limbic abnormalities in at-risk adolescents and young adults who develop a mood disorder. In order to accomplish these aims, we will acquire neurometabolic (MRS) and neurofunctional (fMRI) measurements in 140 subjects without any mood disorder and with a bipolar parent (at-risk, AR) and 40 subjects without a first-degree relative with a mood disorder (healthy, HC) for the proposed longitudinal study. Comparisons between offspring of bipolar and healthy parents will define baseline fMRI and 1H MRS abnormalities and longitudinal follow-up of both groups will identify predictors and markers of incipient mood episodes, as well as neurodevelopmental changes that are unique to the development of mood episodes in those at risk for bipolar disorder (Center Goals 1-3). We believe this information may ultimately, clarify neurophysiological models of bipolar disorder (Center Goal 1) and provide neurophysiological treatment targets in order to prevent the onset of bipolar disorder in those with a familial risk for developing the illness (Center goals 2 & 3).