Psychiatria pre prax 3/2020

Glutamate and glutamate modulators in schizophrenia

Approximately from 1950s the dopamine hypothesis of schizophrenia has been dominant. In the light of current knowledge on many levels (genetic studies, post mortem studies, in vivo imaging stuides, animal models), glutamate hypothesis is more and more discused as a main dysfunction in schizophrenia. Most clearly linked with schizophrenia is the dysfunction of NMDA receptors on GABA-inhibitory interneurons of thalamus. This leads to disinhibition of cortical pyramidaa neurons and to dysfregulation of dopamine release in striatum. Glutamate hypothesis offers different view on etiology of cognitive and negative symptoms. Cognitive and negative symptoms are now considered to be the main cause of ongoing invalidity and insufficient social functioning. New theoretical aspects suggest new starting point for synthesis of novel drugs. Glutamate modulating agents are subject of several clinical studies examining their effectivity and safety in the treatment of schizophrenia, although results are quite heterogeneous for various reasons.

Keywords: glutamate, dopamine, schizophrenia, NMDA, glycine