Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Int Rev Psychiatry. 2009;21(4):387-93. doi: 10.1080/09540260902962180.
White matter deficits have been demonstrated in people with bipolar disorder, schizophrenia and their unaffected relatives. These deficits are supported by evidence from post-mortem studies, including microarray investigations which have repeatedly implicated abnormal myelin-associated gene expression. Furthermore, several risk-associated genes have now been identified that encode for proteins which have effects on white matter integrity. These genes include neuregulin-1 (NRG1) polymorphisms of which have been associated with risk to bipolar disorder. NRG1 has been shown to have effects on axonal migration, myelination and oligodendrocyte function. We and others have also shown that 5' risk-associated genetic variants in NRG1 are associated with reductions in both white matter density and integrity in regions associated with prefrontal connectivity. These findings are discussed in the context of the current literature, along with possible future research directions.
在双相情感障碍、精神分裂症及其未受影响的亲属中，已经发现了白质缺陷。这些缺陷得到了尸检研究的证据支持，包括微阵列研究，这些研究反复表明髓鞘相关基因表达异常。此外，现在已经确定了几个与风险相关的基因，这些基因编码的蛋白质对白质完整性有影响。这些基因包括神经调节蛋白-1（NRG1）的多态性，其与双相情感障碍的风险相关。NRG1 已被证明对轴突迁移、髓鞘形成和少突胶质细胞功能有影响。我们和其他人还表明，NRG1 中 5'风险相关的遗传变异与与前额叶连接相关的区域的白质密度和完整性的降低有关。这些发现与当前文献一起讨论，并提出了可能的未来研究方向。
