Cognition, schizophrenia, and the atypical antipsychotic drugs.

Abstract

Schizophrenia was originally called dementia praecox by Emil Kraepelin, the great 19th century psychiatric nosologist, who coined the term to categorize a group of young psychotic patients who went on to develop dementia. A decade later, Eugen Bleuler, noting that most patients who had similar psychotic and affective features did not become severely demented, renamed the illness schizophrenia and in the process decreased the central importance of cognitive impairment to the broader entity, although he, too, conceptualized schizophrenia as a neurocognitive disorder (1). Recognition of the central importance of cognitive impairment to schizophrenia further diminished in the 1950s, after the development of antipsychotic drugs such as chlorpromazine and haloperidol, which had, as their signature characteristics, the ability to improve delusions and hallucinations, although, at the same time, causing significant extrapyramidal side effects (EPS). The evolution of diagnostic schema for schizophrenia during the 1970s and 1980s further emphasized delusions and hallucinations (now generally referred to as positive symptoms), which, in about 70% of cases, respond to the haloperidol-like drugs (now called typical antipsychotics, for reasons explained below). However, these drugs were found not to improve cognitive function and, sometimes, to impair some aspects of cognition, such as memory and fine motor function (2–4). Research on the cognitive impairment of schizophrenia, nevertheless, went forward, and its major features were reliably described: (i) all domains of cognition, including attention, executive function, secondary (storage) memory, working memory, and semantic memory, may be affected (5); (ii) the pattern of deficits may vary widely among individuals with schizophrenia (5); (iii) the mean deficit in these domains may be 1–3 standard deviations below normal (5–7), although about 15% of patients with schizophrenia test within the normal range in all domains (8); (iv) for most patients, impairment is only slowly progressive after the first …