Disturbed structural connectivity in schizophrenia primary factor in pathology or epiphenomenon? Schizophr

cortical 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 mag-netization transfer imaging (MTI) have been used to inves-tigate directly whether fiber tract abnormalities are indeed present in schizophrenia. To date, findings are inconsistent that may express problems related to methodological issues andsamplesize.Also,pathologicalprocessesdetectablewith these new techniques are not yet well understood. Neverthe-less,withgrowingevidenceof disturbedstructural connectiv-ity, myelination has been in the focus of postmortem investigations. Several studies have shown a significant re-duction of oligodendroglial cells and ultrastructural altera-tions of myelin sheats in schizophrenia. There is also growing evidence for abnormal expression of myelin-related genes in schizophrenia: Neuregulin (NRG1) is important for oligo-dendrocyte development and function, and altered expres-sion of erbB3, one of the NRG1 receptors, has been shown in schizophrenia patients. This is consistent with recent ge-netic studies suggesting that NRG1 may contribute to the ge-netic riskforschizophrenia. Inconclusion, 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 intrinsi-cally linked to the primary risk factors for schizophrenia or to secondary downstream effects (ie, degeneration of fibers secondarily caused by cortical neuronal dysfunc-tion)—an issue that needs to be clarified by future research