The abnormal development of drive and guidance mechanisms in the brain: the pathogenesis of schizophrenia

It remains a mystery as to how genetic and environmental factors cause schizophrenia.

To develop a pathophysiological model of schizophrenia that has greater explanatory power than existing hypotheses of the disorder.

Published findings on schizophrenia are integrated with more recent data from human and animal studies of striatal and cerebellar functions.

The analysis shows that during phylo- and ontogenesis two primarily motor-control mechanisms are applied at the intentional (limbic) level of functioning to organize emotional and cognitive behavior: one for initiating and dosing (drive) and the other for the representational guidance (guidance) of both movements and intentions. The intentional drive and guidance mechanisms are organized through a ventral, respectively, a dorsal cortical-subcortical circuitry.

A deficient implementation of these mechanisms at the limbic domain manifests itself as schizophrenia, whereby the heterogeneity in symptomatology is explained by the extent of the remaining cerebral activity and by the degree of indirect activation of these systems. In general, activation manifests itself as positive symptomatology and the absence of such activation as negative symptomatology. The model provides a more comprehensive explanation for existing clinical and epidemiological data than do the current alternatives. It is compatible with the major prevailing views on the illness, such as the theories that regard this as a progressive neurodevelopmental, or a connectivity disorder, or one resulting from a deficient cerebral lateralization, or an interrupted cortico-thalamo-cerebello-cortical circuitry. The model fits with recent theories in evolutionary psychology and evolutionary psychiatry.