Abnormal Reinnervation as a Basis for Schizophrenia: A Hypothesis

Neuropathologic and neuroimaging studies reveal atrophy or dystrophy of the hippocampal region and enlarged ventricles indicative of tissue loss in many patients with schizophrenia. It is now widely recognized that brain damage can provoke regenerative collateral sprouting of axons, synaptic proliferation, and reorganization, even in the adult mammalian brain. The functional consequences of these plastic regenerative changes are largely unknown; they could be adaptive or cause further impairment. There is evidence of lesion-provoked aberrant synaptic regeneration in epilepsy and Alzheimer's disease. Data suggest that anomalous reinnervation could also have a significant role in the pathophysiology of schizophrenia. Histologic methods to test this hypothesis are in progress.