The biological role of the cadherin gene FAT in bipolar disorder susceptibility

躁郁症(躁郁症)是一种严重的情绪障碍，终生患病率高达1%。这种疾病的特征是异常的情绪波动，导致躁狂和抑郁的时期，并在发作之间恢复正常行为。这种情况对患者有严重影响，在世卫组织全球疾病负担报告中被证明是第六大致残障碍，并将自杀风险增加15倍。迫切需要更清楚地界定双相情感障碍的生物学基础，以此作为改进诊断和治疗的必要前提。双相情感障碍的根本原因仍不清楚。然而，家族性研究揭示了双相情感障碍的高遗传性，这种家族聚集性提供了使用遗传学方法来识别易感基因的机会。我们研究的长期目标是调查那些导致或易患双相情感障碍的基因的生物学。我们之前已经使用遗传学方法鉴定了第一个双相情感障碍易感基因，这是一种位于4号染色体上的细胞接触分子，来自钙粘素家族。这项建议的目的是了解该基因如何导致双相情感障碍的风险。这将通过确定钙粘附素易感基因，被称为‘脂肪’如何在实验室测试中导致属性改变或在动物模型中导致行为改变来实现。确定导致双相情感障碍的基因，并了解它们对这种严重精神疾病的生物学基础的贡献，对于将这些发现转化为提高诊断、治疗和预防疾病的能力至关重要。

Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1%. The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide fifteen-fold. There is a pressing need to define more clearly the biological basis of bipolar disorder as a necessary prerequisite to improved diagnosis and treatment. The underlying causes of bipolar disorder remain unknown. However, family studies reveal the high heritability of bipolar disorder and this familial clustering provides an opportunity to use genetic approaches to identify the predisposing genes. The long-term aim of our research is to investigate the biology of those genes that either cause or predispose to bipolar disorder. We have previously used genetic approaches to identify the first bipolar disorder susceptibility gene, a cell contact molecule located on chromosome 4 that is from the cadherin family. The aim of this proposal is to understand how this gene contributes to the risk of developing bipolar disorder. This will be achieved by identifying how the cadherin susceptibility gene, termed 'FAT' results in altered properties in laboratory assays or in altered behaviours in animal models. Identifying the genes responsible for bipolar disorder and understanding their contribution to the biological basis of this severe psychiatric condition is essential to translate these discoveries into improvements in the ability to diagnose, treat and prevent the illness.