Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders

Schizophrenia, a neurodevelopmental disorder, is characterized by complex genetics and an incompletely understood pathophysiology.

Various genetic components have been identified as risk factors for developing schizophrenia.

Its understood pathophysiology primarily involves excessive dopaminergic neurotransmission in the brain and periphery.

The dopamine hypothesis posits that anomalies in dopamine receptors contribute to the symptoms of schizophrenia.

As a result, dopamine D₂ antagonists, like chlorpromazine and haloperidol, which block postsynaptic dopamine receptors, effectively treat schizophrenia.

The serotonin hypothesis suggests that imbalances in serotonin levels are involved in schizophrenia pathogenesis.

Second-generation antipsychotics antagonize the 5HT_2A receptor, offering unique clinical features and binding profiles.

The glutamate hypothesis links glutamate neurotransmission dysfunction to schizophrenia, involving reduced NMDA receptor function, which decreases activity in mesocortical dopaminergic neurons.

Understanding altered glutamate transmission may help develop improved antipsychotic drugs. For instance, newer agents enhancing AMPA-type glutamate currents help rectify psychotic behavior without exhibiting neurotoxicity.