Haroutunian Vahram, Katsel Pavel, Dracheva Stella, Stewart Daniel G, Davis Kenneth L
Department of Psychiatry, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6575, USA.
Int J Neuropsychopharmacol. 2007 Aug;10(4):565-73. doi: 10.1017/S1461145706007310. Epub 2007 Feb 12.
The disconnectivity syndrome hypothesis of schizophrenia suggests that communication between multiple brain circuits and regions may be disrupted. Microarray studies analysed gene expression in 15 different brain regions derived from 13 persons with schizophrenia and controls. The superior temporal gyrus, cingulate gyrus and hippocampus evidence the greatest numbers of abnormally expressed genes. Gene ontology categorization suggested that gene classes associated with oligodendrocytes and myelin function were among the most profoundly affected. qPCR and additional microarray studies have validated these oligodendrocyte- and myelin-associated findings in independent cohorts. At least some of the affected genes are associated with the regulation of axoglial contacts, axon calibre and the integrity of functional elements involved in signal propagation. The confluence of emerging evidence shows that myelination abnormalities are major components of the neurobiology of schizophrenia and suggest that re-evaluation of some long-held hypotheses and beliefs regarding the biological substrates of schizophrenia may be warranted.
精神分裂症的脱节综合征假说表明，多个脑回路和区域之间的交流可能会受到干扰。微阵列研究分析了来自13名精神分裂症患者和对照组的15个不同脑区的基因表达。颞上回、扣带回和海马体中异常表达的基因数量最多。基因本体分类表明，与少突胶质细胞和髓鞘功能相关的基因类别受到的影响最为深远。定量聚合酶链反应（qPCR）和其他微阵列研究在独立队列中验证了这些与少突胶质细胞和髓鞘相关的发现。至少一些受影响的基因与轴突-神经胶质接触、轴突管径以及信号传播中功能元件的完整性的调节有关。新出现的证据表明，髓鞘形成异常是精神分裂症神经生物学的主要组成部分，并表明可能有必要重新评估一些关于精神分裂症生物学基础的长期假设和观点。
