Novas perspectivas e diretrizes na terapêutica da esquizofrenia: avanços relacionados com os sistemas não-dopaminérgicos

Abstract

The dopamine hypothesis of schizophrenia first emerged in relation to the ability of anti-dopaminergic compounds to reverse psychotic symptoms. Antipsychotics are still the gold standard for treating schizophrenia, despite their limited success in the management of negative symptoms and their side effect profile. Several non-dopaminergic hypotheses have emerged based on a variety of studies. We will focus on these non-dopamine systems and their therapeutic implications for the management of schizophrenia. Glutamate and NMDA receptor hypofunctionThe N-methyl-D-aspartic acid receptor (NMDAR) hypofunction hypothesis developed from the finding that drugs which block glutamate NMDARs, such as phencyclidine (PCP), induce effects almost identical to the positive and negative symptoms seen in schizophrenia. Animals given chronic doses of NMDAR antagonists developed loss of grey matter similarly reported in schizophrenia, while a relative deficit in NMDAR binding has been found in the left hippocampus of schizophrenic patients using SPECT imaging.