Lifelong Learning: Fifty Years of Research on Schizophrenia: The Ascendance of the Glutamatergic Synapse-View Article

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Significant progress has been made in understanding the causes of schizophrenia and related mental disorders through the rise of biologic psychiatry and the discovery of effective drugs. The dopamine hypothesis suggests dopaminergic dysfunction as the cause. However, recovery from schizophrenia has not significantly improved. The discovery of clozapine and second-generation antipsychotics shows promise in treating unresponsive patients. Research has identified alterations in glutamatergic synapses, reductions in GABAergic and cholinergic neurons, and abnormalities in glutamate receptor levels as key factors. Animal models and genetic studies support the role of glutamatergic synapses. This knowledge can lead to the development of new treatments. Mutations in genes associated with NMDA receptor function disrupt brain circuitry and impair synapse formation, plasticity, and maintenance. GABAergic inhibitory feedback is affected, leading to increased firing of pyramidal neurons. The document also discusses neurotransmitter systems, potential treatments, and the importance of understanding genetic factors in schizophrenia.

Keywords

schizophrenia

mental disorders

biologic psychiatry

dopamine hypothesis

clozapine

glutamatergic synapses

GABAergic neurons

glutamate receptor levels

NMDA receptor function

genetic factors