Abstract
A puzzling feature of schizophrenia, is the long latency between the beginning of neuropathological changes and the clinical presentation that may be two decades later. Abnormalities in oligodendrocyte function may explain this latency, because mature oligodendrocytes produce myelination, and if myelination were abnormal from the outset, it would cause the synaptic dysfunction and abnormal neural tracts that are underpinning features of schizophrenia. The hypothesis is that latency is caused by events that occur in some patients as early as in-utero or infancy, because clones of abnormal, myelinating oligodendrocytes may arise at that time; their number doubles every ~2 years, so their geometric increase between birth and age twenty, when clinical presentation occurs, is about 1000-fold plus the effect of compounding. For those patients in particular, the long latency is because of a small but ongoing increase in volume of the resulting, abnormally myelinated neural tracts until, after a long latent interval, a critical mass is reached that allows the full clinical features of schizophrenia. During latency, there may be behavioral aberrancies because of abnormally myelinated neural tracts but they are insufficiently numerous for the clinical syndrome. The occurrence of behavioral symptoms during the long latent period, substantiates the hypothesis that abnormal oligodendrocytes explain the latency in some patients. Treatment with fingolimod or siponimod benefits both oligodendrocytes and neural tracts. Clinical trial would validate their potential benefit in appropriate patients with schizophrenia and, concurrently, would validate the hypothesis.