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，但神经生理学 本病发生的基础尚不清楚。青春期是最常见的 双相情感障碍的发作。此外，双相父母的后代患双相情感障碍的风险更高。 与普通人群相比，这是一种精神障碍。因此，澄清的一种方法是 双相情感障碍早期进展的神经发育模型及其识别潜力 早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 患有双相情感障碍(即父母有双相情感障碍)，但自己还没有情绪障碍。 双相情感障碍的特征是情绪和注意力紊乱。前缘网络，它 涉及腹侧前额叶皮质、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。具体地说，功能成像(FMRI)研究表明，前缘网络 可能在双相情感障碍患者中过度激活，从而产生这种情况的症状。 此外，磁共振波谱(MRS)研究表明，高代谢可能是 前缘过度激活。具体地说，MRS研究发现双相患者表现出 与健康受试者相比，谷氨酸(Glu)和肌醇(Ml)浓度过高。 考虑到这些因素，本研究的目标是：1)使用fMRI和1H MRS来评估 青春期和青壮年双相情感障碍子代的前缘功能和代谢异常 父母(高危)；2)使用fMRI和1HMRS评估前缘的功能和代谢 异常是高危青少年和青壮年早期情绪障碍的潜在标志；以及 3)检查高危青少年和青壮年的前缘异常进展情况。 出现情绪障碍。为了实现这些目标，我们将获得神经代谢(MRS)和 140例无任何情绪障碍父母为双相情感障碍的受试者的神经功能(FMRI)检测 (高危，AR)和40名没有一级亲属的有情绪障碍(健康，HC)的受试者 建议进行纵向研究。双相情感障碍父母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异常以及纵向随访将确定预测因素和 早期情绪发作的标志，以及独有的神经发育变化 双相情感障碍高危人群的情绪发展(中心目标1-3)。我们相信这一点 信息可能最终阐明双相情感障碍的神经生理学模型(中心目标1)，并提供 预防家族性双相情感障碍发病的神经生理学治疗目标 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).