Schizophrenia: susceptibility genes and oligodendroglial and myelin related abnormalities
نویسندگان
چکیده
Given that the genetic risk for schizophrenia is highly polygenic and the effect sizes, even for rare or de novo events, are modest at best, it has been suggested that multiple biological pathways are likely to be involved in the etiopathogenesis of the disease. Most efforts in understanding the cellular basis of schizophrenia have followed a "neuron-centric" approach, focusing on alterations in neurotransmitter systems and synapse cytoarchitecture. However, multiple lines of evidence coming from genetics and systems biology approaches suggest that apart from neurons, oligodendrocytes and potentially other glia are affected from schizophrenia risk loci. Neurobiological abnormalities linked with genetic association signal could identify abnormalities that are more likely to be primary, versus environmentally induced changes or downstream events. Here, we summarize genetic data that support the involvement of oligodendrocytes in schizophrenia, providing additional evidence for a causal role with the disease. Given the undeniable evidence of both neuronal and glial abnormalities in schizophrenia, we propose a neuro-glial model that invokes abnormalities at the node of Ranvier as a functional unit in the etiopathogenesis of the disease.
منابع مشابه
Disturbed structural connectivity in schizophrenia primary factor in pathology or epiphenomenon?
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 abnormaliti...
متن کاملIntroduction to the special section: Myelin and oligodendrocyte abnormalities in schizophrenia.
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...
متن کاملImproving myelin/oligodendrocyte-related dysfunction: a new mechanism of antipsychotics in the treatment of schizophrenia?
Schizophrenia is a severe psychiatric disorder with complex clinical manifestations and its aetiological factors remain unclear. During the past decade, the oligodendrocyte-related myelin dysfunction was proposed as a hypothesis for schizophrenia, supported initially by a series of neuroimaging studies and genetic evidence. Recently, the effects of antipsychotics on myelination and oligodendrog...
متن کاملDISC1 (Disrupted-in-Schizophrenia-1) Regulates Differentiation of Oligodendrocytes
Disrupted-in-schizophrenia 1 (DISC1) is a gene disrupted by a translocation, t(1;11) (q42.1;q14.3), that segregates with major psychiatric disorders, including schizophrenia, recurrent major depression and bipolar affective disorder, in a Scottish family. Here we report that mammalian DISC1 endogenously expressed in oligodendroglial lineage cells negatively regulates differentiation of oligoden...
متن کاملMolecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia.
CONTEXT Genetic, neuroimaging, and molecular neurobiological evidence support the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could arise from failures of saltatory conduction and abnormalities at the nodes of Ranvier (NOR) interface where myelin and axons interact. OBJECTIVE To identify abnormalities in the expression of oligodendroglial genes and proteins that partici...
متن کامل