Understanding the molecular basis of bipolar affective disorder

躁郁症(躁郁症)是一种严重的情绪障碍，终生患病率高达1.6%。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。我们之前曾报道过在4号染色体上发现一种新的双相情感障碍易感基因的有力证据，这一发现随后在几项独立研究中重现。因此，我们假设在4号染色体上有一个易患双相情感障碍的基因。这项建议的目的是确定4号染色体双相易感基因，并了解该基因是如何导致双相情感障碍的。识别导致双相情感障碍的基因将使我们能够定义和理解这种严重精神疾病的生物学基础。这最终将导致诊断、治疗和预防疾病能力的重大改进。

Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1.6%. 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 reported strong evidence for a novel bipolar disorder susceptibility gene on chromosome 4, a finding which has subsequently been reproduced in several independent studies. Consequently, we hypothesise that there is a gene located on chromosome 4 that predisposes to bipolar disorder. The aim of this proposal is to identify the chromosome 4 bipolar susceptibility gene and understand how the gene causes bipolar disorder. Identifying the genes responsible for bipolar disorder will allow us to define and understand the biological basis of this severe psychiatric condition. This will ultimately lead to major improvements in the ability to diagnose, treat and prevent the illness.