Introduction to the special section: Myelin and oligodendrocyte abnormalities in schizophrenia.
ABSTRACT A central tenet of modern views of the neurobiology of schizophrenia is that the symptoms of schizophrenia arise from a failure of adequate communication between different brain regions and disruption of the circuitry that underlies behaviour and perception. Historically this disconnectivity syndrome has been approached from a neurotransmitter-based perspective. However, efficient communication between brain circuits is also contingent on saltatory signal propagation and salubrious myelination of axons. The papers in this Special Section examine the neuroanatomical and molecular biological evidence for abnormal myelination and oligodendroglial function in schizophrenia through studies of post-mortem brain tissue and animal model systems. The picture that emerges from the studies described suggests that although schizophrenia is not characterized by gross abnormalities of white matter such as those evident in multiple sclerosis, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths.
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ABSTRACT: While many diffusion tensor imaging (DTI) investigations have noted disruptions to white matter integrity in individuals with chronic psychotic disorders, fewer studies have been conducted in young people at the early stages of disease onset. Using whole tract reconstruction techniques, the aim of this study was to identify the white matter pathology associated with the common clinical symptoms and executive function impairments observed in young people with psychosis.Journal of psychiatry & neuroscience: JPN 08/2014; 39(4):130280. · 7.49 Impact Factor
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ABSTRACT: The past decade has witnessed an explosion of knowledge on the impact of glia for the neurobiological foundation of schizophrenia. A plethora of studies have shown structural and functional abnormalities in all three types of glial cells. There is convincing evidence of reduced numbers of oligodendrocytes, impaired cell maturation and altered gene expression of myelin/oligodendrocyte-related genes that may in part explain white matter abnormalities and disturbed inter- and intra-hemispheric connectivity, which are characteristic signs of schizophrenia. Earlier reports of astrogliosis could not be confirmed by later studies, although the expression of a variety of astrocyte-related genes is abnormal in psychosis. Since astrocytes play a key role in the synaptic metabolism of glutamate, GABA, monoamines and purines, astrocyte dysfunction may contribute to certain aspects of disturbed neurotransmission in schizophrenia. Finally, increased densities of microglial cells and aberrant expression of microglia-related surface markers in schizophrenia suggest that immunological/inflammatory factors are of considerable relevance for the pathophysiology of psychosis. This review describes current evidence for the multifaceted role of glial cells in schizophrenia and discusses efforts to develop glia-directed therapies for the treatment of the disease.Schizophrenia Research 06/2014; · 4.43 Impact Factor
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ABSTRACT: Deficits in the execution of a sequence of movements are common in schizophrenia. Previous studies reported reduced functional activity in the motor cortex and cerebellum in schizophrenic patients with deficits in movement sequencing. The corticospinal tract (CST) and superior cerebellar peduncle (SCP) are fiber tracts that are involved in movement sequencing. However, the integrity of these tracts has not been evaluated in schizophrenic patients with respect to the performance of movement sequencing yet. Diffusion tensor magnetic resonance images (DT-MRI) were acquired from 24 patients with schizophrenia and 23 matched control subjects. Tractography was applied to reconstruct the CST and SCP and DT-MRI-specific parameters such as fractional anisotropy (FA) and radial diffusivity (RD) were reported. The patient group was further subdivided based on the score of sequencing of complex motor acts subscale of the Neurological Evaluation Scale into those with deficits in sequencing motor acts, the SQ(abn) group (n = 7), and those with normal performance, the SQ(norm) group (n = 17). Schizophrenia patients of the SQ(norm) subgroup had significantly reduced FA and increased RD values in the right CST in comparison to the control group; the SQ(abn) subgroup did not differ from the controls. However, the SQ(abn) subgroup showed impaired integrity of the left SCP, whereas the SQ(norm) subgroup did not. Abnormalities in the right CST in the SQ(norm) and in the left SCP in SQ(abn) groups suggest that the patients with SQ(abn) represent subgroups with distinct deficits. Moreover, these results demonstrate the involvement of the SCP in the pathogenesis of movement sequencing in schizophrenia.The Cerebellum 02/2014; · 2.60 Impact Factor