双相障碍父母的有前驱症状子女的神经认知及其神经环路机制研究

项目名称： 双相障碍父母的有前驱症状子女的神经认知及其神经环路机制研究

项目编号： No.81471375

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 徐贵云

作者单位： 广州医科大学

项目金额： 71万元

中文摘要： 双相障碍（BD）是高患病率、高复发率的慢性终身性疾病，然69%BD患者曾被误诊或诊断延迟，主要原因是BD的发病机制不清楚。BD患者存在广泛的神经认知及其神经环路损害如额叶-颞叶(边缘系统)脑区的功能失调和激活不平衡，但心境发作期、心境稳定期、儿童期及患者一级亲属的损害都不同，BD患者的损害可能与反复发作、长期病程及药物治疗有关。假设BD患者前驱期存在某些不同于BD患者及其一级亲属的、最初的神经认知损害及其关联的、最初的神经环路损害。因此，我们拟对父母BD有前驱症状子女、父母BD无前驱症状子女、儿童青少年BD患者及年龄和受教育程度相当的健康对照各组30例，进行MCCB为主的神经认知测验，并进行结构态、弥散张量成像、静息态及在工作记忆和情绪序列任务激发下的磁共振检查，以探索BD患者前驱期、最初的神经认知损害及其相关联的神经环路机制，促进BD的早期诊断和早期治疗，减少患者、家属的痛苦和疾病负担。

中文关键词： 双相障碍；前驱症状；神经认知；神经环路；功能磁共振

英文摘要： Bipolar disorder (BD) is one of the most common mental illnesses, with lifetime prevalence as high as 3.9% and high recurrence and comorbidity. Unfortunately, about 69% of BD patients are misdiagnosed often as unipolar depression because its mechanism is still unclear and there are lack of subjective biomarkers for the diagnosis. Neurocognitive deficits are observed in both acute and remission periods of BD, but the extent and neurocognitive profiles are different depending on the states.Many factors can contribute to the abnormalities, including recurrences, long duration, and medications. Some studies have shown that the unaffected relatives of the probands with BD may display deficits in some domains to a less extent, when compared to the probands with BD. A few studies suggested that there may be neurocognitive deficits in high-risk individuals with BD, but they may be different from that seen in BD patients and in the unaffected relatives. Research has shown abnormalities in some neural circuits such as fronto-temporal/limbic-either dysregulation or abnormal functional activities-in individuals with BD or even in the unaffected relatives of probands with BD. There are different in extents and levels of abnormal brain regions between diffenent states and diffenent stages in BD patients, and the unaffected relatives of probands with BD. Again, many factors can contribute to the abnormalities, including recurrences, long duration, and medications. Given the above considerations, we hypothesize that individuals who are at the prodromal stage of BD may have original neurocognitive deficits and related neural circuit abnormalities that are different from BD patients. This study will be a high-risk design, consisting of four groups. We will investigate the neuropsychological performance in 30 child or adolescent individuals with BD, 30 high-risk individuals with prodromal symptoms with one parent with BD, 30 high-risk individuals without prodromal symptoms with one parent with BD, and 30 healthy controls without parent with BD and without any psychiatric family history. We will administer MCCB( Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery）to assess neurocognitive function, including processing speed, attention, working memory, verbal learning, memory, visual learning, and executive function. We will apply a Philip Ingenia 3.0 T MRI Scanner to conduct a multimoding magnetic resonance imaging (MRI), including resting state, diffusion tensor imaging (DTI) , brain structural MRI as well as emotional and cognitive task MRI. The mains aim thus is to examine the initial impairment in neurocognitive function and its related neural circuit deficits in patients with BD. Such strategy will help understand the mechanisms of BD and thus assist the early diagnosis of and intervention on BD.

英文关键词： bipolar disorder;prodrome;neurocognition;neural circuit;fMRI