First- and second-generation antipsychotic medication and cognitive processing in schizophrenia

Schizophrenia has been consistently characterized by deficits in the cognitive domains of executive function, working memory, attention, and episodic memory. Although some cognitive abnormalities, such as motor slowing, may be associated with antipsychotic medication administration, generally the cognitive deficits shown by patients with schizophrenia can be attributed at least in part to the disease process. Modulation of the dopamine neurotransmitter system, notably through D2 receptor blockade, has been associated with psychotic symptom reduction and cognitive performance improvements in patients with schizophrenia. Although first-generation antipsychotic medication treatment initially was thought not to result in cognitive improvement, recent studies comparing second-generation antipsychotics to low doses of first-generation antipsychotic medication showed cognitive benefits for first-generation drugs, although perhaps not as great as that found after treatment with second-generation medication. Cognitive improvement associated with administration of antipsychotic medication may be a manifestation of improvement in general cortical information processing. Recent work has shown that specific genetic polymorphisms may interact with antipsychotic medication treatment to influence the degree to which cognitive abilities display improvement after treatment. In particular, the catechol-O-methyltransferase val108/158met polymorphism has been shown to predict working memory improvement after administration of antipsychotic medication to patients with schizophrenia.