Signal Transmission, Rather Than Reception, is the Underlying Neurochemical Abnormality in Schizophrenia

Abstract

Objective: This review aims to summarise the outcome of studies on changes in the molecular architecture of the brain of subjects with schizophrenia and formulate a hypothesis on mechanisms involved in the pathology of the illness. Method: The outcomes from key studies using neuroimaging techniques and tissue obtained post-mortem that have been directed toward identifying abnormalities in the molecular architecture of the brain in subjects with schizophrenia were summarised. Using the results from these studies hypotheses were formulated on the underlying pathological process that precipitate schizophrenia. Results: Studies using neuroimaging techniques or tissue obtained post-mortem have revealed changes in the dopaminergic, serotoninergic, glutamatergic, GABAergic and cholinergic systems of the brain in schizophrenia. Some of these studies have identified abnormalities in presynaptic proteins or functioning that may be central to the pathology of schizophrenia. Conclusions: There appears to be diverse changes in the molecular cytoarchitecture of the brains from subjects with schizophrenia. It could be that it is by affecting these multiple systems that the atypical antipsychotic drugs produce their improved clinical outcomes. Abnormal functioning of presynaptic processes could be central to the pathology of schizophrenia. If the ‘presynaptic’ hypothesis is proven, future antipsychotic drug design should be directed away from post-synaptic receptor antagonism toward the modulating the functions of presynaptic neurones.