Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Saitama, Japan.
PLoS One. 2013;8(2):e53855. doi: 10.1371/journal.pone.0053855. Epub 2013 Feb 7.
Bipolar disorder is a severe mental illness characterized by recurrent manic and depressive episodes. In bipolar disorder, family and twin studies suggest contributions from genetic and environmental factors; however, the detailed molecular pathogenesis is yet unknown. Thus, identification of biomarkers may contribute to the clinical diagnosis of bipolar disorder. Monozygotic twins discordant for bipolar disorder are relatively rare but have been reported. Here we performed a comparative proteomic analysis of whole cell lysate derived from lymphoblastoid cells of monozygotic twins discordant for bipolar disorder by using two-dimensional differential in-gel electrophoresis (2D-DIGE). We found approximately 200 protein spots to be significantly differentially expressed between the patient and the co-twin (t test, p<0.05). Some of the proteins were subsequently identified by liquid chromatography tandem mass spectrometry and included proteins involved in cell death and glycolysis. To examine whether these proteins could serve as biomarkers of bipolar disorder, we performed Western blot analysis using case-control samples. Expression of phosphoglycerate mutase 1 (PGAM1), which is involved in glycolysis, was significantly up-regulated in patients with bipolar disorder (t test, p<0.05). Although PGAM1 cannot be regarded as a qualified biomarker of bipolar disorder from this preliminary finding, it could be one of the candidates for further study to identify biomarkers of bipolar disorder.
双相情感障碍是一种严重的精神疾病，其特征是反复发作的躁狂和抑郁发作。在双相情感障碍中，家族和双胞胎研究表明遗传和环境因素都有贡献；然而，详细的分子发病机制尚不清楚。因此，鉴定生物标志物可能有助于双相情感障碍的临床诊断。双相情感障碍不一致的同卵双胞胎相对较少，但有报道。在这里，我们通过二维差异凝胶电泳（2D-DIGE）对双相情感障碍不一致的同卵双胞胎的淋巴母细胞系全细胞裂解物进行了比较蛋白质组学分析。我们发现大约 200 个蛋白点在患者和同卵双胞胎之间存在明显差异表达（t 检验，p<0.05）。一些蛋白质随后通过液相色谱串联质谱法进行鉴定，包括参与细胞死亡和糖酵解的蛋白质。为了研究这些蛋白质是否可以作为双相情感障碍的生物标志物，我们使用病例对照样本进行了 Western blot 分析。参与糖酵解的磷酸甘油酸变位酶 1（PGAM1）的表达在双相情感障碍患者中显著上调（t 检验，p<0.05）。尽管从这个初步发现来看，PGAM1 不能被视为双相情感障碍的合格生物标志物，但它可能是进一步研究以确定双相情感障碍生物标志物的候选者之一。
