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Academic Highlights: Optimizing Pharmacotherapy to Maximize Outcome in Schizophrenia

J Clin Psychiatry 2005;66(1):122-123

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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.1,2 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.2