Speaker 4: Gerhard Gründer, Germany

s | 27 nicotinic and muscarinic receptors have been shown in animal models to contribute to restoring cognitive function in various rodent models of CIAS while excessive D2 receptor blockade has a negative influence on cognition. Data from recent GWAS studies will be presented which demonstrate that the efficacy of atypical APDs to improve psychopathology in schizophrenia is mediated by gene products that affect synaptic structure and function, e.g. neurexin and other synaptic adhesion gene products. The synaptic mechanisms that are required for normal reality testing, rewarded behavior, and higher cognitive function may be impaired by too much or too little stimulation of all five DA receptors, certainly not just D2 receptors. The atypical APDs are better able to achieve optimal stimulation of these receptors through a variety of mechanisms, many of which are serotonergic. D2 receptor blockade is not necessary but sometimes sufficient which has led to long standing overvaluation of its importance. The heterogeneity in response to APDs may be related to genetic variations which govern the various ways in which synapses can be made to work effectively.