Intellectual deficits in first-episode schizophrenia: evidence for progressive deterioration.

The developmental processes leading to neuropsychological deficits in schizophrenia are poorly understood. Both early developmental defects and subsequent deterioration may occur. Intelligence test profiles are often used to estimate premorbid ability and deterioration from prior levels of functioning. These characteristics were assessed in samples of first-episode (n = 51) and chronic (n = 50) schizophrenic patients. Although the groups showed few differences on tests to estimate premorbid intellectual ability, the chronic group performed worse on measures considered sensitive to deterioration. Dextral (right-handed) patients tended to have better performance; this effect was marked in the first-episode sample, especially on verbal tests. Male patients showed more evidence of deterioration than female patients. Subgroups differing in the time course of premorbid social dysfunction also differed in intelligence test profiles, suggesting that estimates of social and cognitive deterioration may have concurrent validity. The results support the hypothesis that patients differ in the course of cognitive decline and suggest that deterioration of function may follow the onset of overt psychosis in some patients. Prospective longitudinal studies of first-episode schizophrenic patients could directly test this hypothesis.

Antipsychotic medication effects on neuropsychological functions.

The investigator of antipsychotic drug effects on neuropsychological functions faces a range of conceptual, methodological, and technical obstacles. Some of these hurdles are pointed out in a brief review of existing literature, and a more detailed consideration of instrumentation issues is presented. The need for hypothesis-driven assessment strategies is highlighted. Interpretive difficulties are posed by the polyfactorial nature of the most widely used neuropsychological tests, and emphasis is placed on the use and development of methods that enable isolation of specific neuropsychological constructs. Examples of this strategy are drawn from ongoing work in the Neuropsychology Unit of the Clinical Research Center for the Study of Schizophrenia at Hillside Hospital, where hypotheses about the behavioral site of action of dopamine agonists and antagonists are used to guide the construction of novel computerized tests.