Patients with schizophrenia are typically characterized by a relative paucity of white matter and often frank hypomyelination (Connor et al., 2011; Fields, 2008; Gogtay et al., 2008; McIntosh et al., 2008; Munoz Maniega et al., 2008; Takahashi et al., 2011), and a number of both pathological and neuroimaging studies have highlighted deficiencies in both oligodendroglial density and myelin structure in affected patients (Fields, 2008; Langmead and Salzberg, 2012; Rapoport et al., 2005; Xia et al., 2014), including at the ultrastructural level (Pruitt et al., 2007; Uranova et al., 2011; Uranova et al., 2007). Furthermore, recent studies have emphasized the role of oligodendrocytes in the metabolic support of neurons, suggesting myelin-independent mechanisms whereby oligodendrocytic dysfunction might yield neuronal pathology (Lee et al., 2012; Simons and Nave, 2015). Yet despite compelling genetic, cellular, pathological, and radiological studies that have correlated glial and myelin pathology with schizophrenia, many have assumed that clinical hypomyelination among schizophrenics is secondary to neuronal pathology, so that the contribution of cell-autonomous glial dysfunction to schizophrenia has not been well studied.
