Project 3: Neurobiological Characterization of Offspring of Biopolar Parents

项目 3：双极性父母后代的神经生物学特征

• 批准号: 8099707
• 负责人: STEPHEN M STRAKOWSKI
• 金额: $ 15.7万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8099707
• 关键词: Address; Adolescence; Adolescent; Adult Children; Affect; Amygdaloid structure; Anterior; Attention; Bipolar Disorder; Brain region; Cell physiology; Characteristics; Child; Clinical; Corpus striatum structure; Creatine; Data; Development; Diagnosis; Early identification; Emotional; Energy Metabolism; Epidemiologic Studies; Exhibits; Family history of; First Degree Relative; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Glutamates; Glutamine; Goals; Inositol; Longitudinal Studies; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Mind; Modeling; Mood Disorders; Moods; Morbidity - disease rate; N-acetylaspartate; Neurobiology; Neurons; Parents; Patients; Phosphocreatine; Prefrontal Cortex; Process; Production; Prospective Studies; Recruitment Activity; Research Personnel; Risk; Symptoms; Syndrome; Testing; Thalamic structure; base; follow-up; mortality; myoinositol; neurochemistry; neurophysiology; offspring; prevent; programs; prospective; response; trait; young adult

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).

尽管与躁郁症相关的发病率和死亡率显着，但神经生理学 这种疾病发展的基础知之甚少。青春期是最常见的时期 躁郁症的发作。此外，双极父母的后代患双极性的风险较高 与普通人群相比，混乱。因此，一种澄清的方法 躁郁症早期进展的神经转化模型并确定潜力 初期情绪发作的神经生物学预测指标是研究有风险的年轻受试者 患上双相情感障碍（即有双极性父母），但尚无情绪障碍本身。 躁郁症的特征是情绪和注意力的破坏。前边缘网络，该网络 涉及腹侧前额叶皮层，丘脑，杏仁核和纹状体，似乎可以调节这些 过程。因此，我们假设躁郁症的症状是由于功能障碍引起的 在此网络中。具体而言，功能成像（fMRI）研究表明前边缘网络 双极患者可能会过度激活，从而产生这种情况的症状。 另外，磁共振光谱（MRS）研究表明，超定代谢可能是基础 过度的前边缘激活。具体而言，MRS研究发现双极患者表现出 与健康受试者相比，过度的谷氨酸（GLU）和肌醇（ML）浓度。 考虑到这些考虑，这项研究的目标是：1）使用fMRI和1H MRS评估 双极的青少年和年轻成年后代的功能性和代谢前边缘异常 父母（处于危险中）； 2）使用fMRI和1H MRS评估功能和代谢前缘 异常是高危青少年和年轻人的初期情绪障碍的潜在标记；和 3）检查高危青少年和年轻人的前边缘异常的进展 发展情绪障碍。为了实现这些目标，我们将获得神经代谢（MRS）和 140名没有任何情绪障碍的受试者和双极父母的神经功能（fMRI）测量 （高危，AR）和40名没有一级亲戚的受试者，具有情绪障碍（健康，HC） 拟议的纵向研究。躁郁症和健康父母后代的比较将定义 基线fMRI和1H MRS异常和两组的纵向随访将确定预测因子和 初期情绪发作的标记以及神经发育变化是独有的 患有双相情感障碍风险的情绪发作的发展（中心目标1-3）。我们相信这一点 信息最终可能会阐明躁郁症的神经生理模型（中心目标1），并提供 神经生理治疗靶标的，以防止家族性患者的躁郁症发作 患病的风险（中心目标2和3）。