Optimizing Pharmacotherapy to Maximize Outcome in Schizophrenia

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Although abundant evidence shows that dysfunction in multiple neurotransmitter systems (including the serotonergic and the glutamatergic systems) contributes to the pathogenesis of schizophrenia, alterations in dopaminergrc systems are the best-documented neurochemical dysfunctions associated with this illness, according to Anissa Abi-Dargham, M.D. The modern dopamine hypothesis of schizophrenia proposes that positive symptoms of psychosis in patients with schizophrenia arise from a condition of up-regulated dopaminerglc neuronal activity in subcortical pathways, whereas negative symptoms and cognitive impairment result from a dopamine deficit in the cortical dopamine (DA) pathways. Traditional support for this hypothesis derives from the fact that typical antipsychotic agents, whose main property is the antagonism of D₂ dopamine receptors, suppress positive symptoms but do not significantly improve and may even worsen negative symptoms.