Konrad Andreas, Winterer Georg
Department of Psychiatry, Johannes Gutenberg-University, Mainz, Germany.
Schizophr Bull. 2008 Jan;34(1):72-92. doi: 10.1093/schbul/sbm034. Epub 2007 May 7.
Indirect evidence for disturbed structural connectivity of subcortical fiber tracts in schizophrenia has been obtained from functional neuroimaging and electrophysiologic studies. During the past few years, new structural imaging methods have become available. Diffusion tensor imaging and magnetization transfer imaging (MTI) have been used to investigate directly whether fiber tract abnormalities are indeed present in schizophrenia. To date, findings are inconsistent that may express problems related to methodological issues and sample size. Also, pathological processes detectable with these new techniques are not yet well understood. Nevertheless, with growing evidence of disturbed structural connectivity, myelination has been in the focus of postmortem investigations. Several studies have shown a significant reduction of oligodendroglial cells and ultrastructural alterations of myelin sheats in schizophrenia. There is also growing evidence for abnormal expression of myelin-related genes in schizophrenia: Neuregulin (NRG1) is important for oligodendrocyte development and function, and altered expression of erbB3, one of the NRG1 receptors, has been shown in schizophrenia patients. This is consistent with recent genetic studies suggesting that NRG1 may contribute to the genetic risk for schizophrenia. In conclusion, there is increasing evidence from multiple sides that structural connectivity might be pathologically changed in schizophrenia illness. Up to the present, however, it has not been possible to decide whether alterations of structural connectivity are intrinsically linked to the primary risk factors for schizophrenia or to secondary downstream effects (ie, degeneration of fibers secondarily caused by cortical neuronal dysfunction)-an issue that needs to be clarified by future research.
精神分裂症患者皮质下纤维束结构连接紊乱的间接证据已从功能神经影像学和电生理研究中获得。在过去几年中，新的结构成像方法已问世。扩散张量成像和磁化传递成像（MTI）已被用于直接研究精神分裂症患者是否确实存在纤维束异常。迄今为止，研究结果并不一致，这可能表明存在与方法学问题和样本量相关的问题。此外，这些新技术可检测到的病理过程尚未得到很好的理解。然而，随着结构连接紊乱证据的不断增加，髓鞘形成已成为死后研究的焦点。多项研究表明，精神分裂症患者少突胶质细胞显著减少，髓鞘超微结构改变。越来越多的证据还表明，精神分裂症患者中与髓鞘相关的基因表达异常：神经调节蛋白（NRG1）对少突胶质细胞的发育和功能很重要，并且已在精神分裂症患者中发现NRG1受体之一erbB3的表达发生改变。这与最近的基因研究一致，表明NRG1可能导致精神分裂症的遗传风险。总之，多方面越来越多的证据表明，精神分裂症患者的结构连接可能发生了病理性改变。然而，到目前为止，尚无法确定结构连接的改变是与精神分裂症的主要危险因素内在相关，还是与继发性下游效应（即由皮质神经元功能障碍继发引起的纤维变性）相关——这一问题需要未来的研究加以阐明。
