Schizophrenia: susceptibility genes and oligodendroglial and myelin related abnormalities.
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.
Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center Bronx, NY, USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai New York, NY, USA ; Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai New York, NY, USA.
Panos
P
Roussos
Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center Bronx, NY, USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai New York, NY, USA ; Department of Neuroscience, Icahn School of Medicine at Mount Sinai New York, NY, USA.
Vahram
V
Haroutunian
GWAS; disconnectivity; node of Ranvier; polygenic; systems biology