Prefrontal Dopamine Signaling in Schizophrenia - The Corticocentric Model

Diminished prefrontal dopamine (DA) signaling apparently contributes to schizophrenia illness. In the proposed corticocentric model, diminished DA is changing the D2/D1 receptor activation ratio in favor of D2 activation which - through a cascade of intracellular molecular events - ultimately decreases the neuronal signal-to-noise ratio (SNR) thereby destabilizing cortical microcircuits resulting in cognitive deficits and other clinical symptoms. The present overview will outline cortical DA effects both on the neural network and systems biology level and their relationship to schizophrenia illness. The proposed model will be finally discussed within the framework of the currently still dominant hypothesis of the striatal hyperdopaminergic state in schizophrenia.