The role of negative symptoms and cognitive dysfunction in schizophrenia outcome

Schizophrenia is a lifelong illness, with symptoms beginning in late adolescence/early adulthood and persisting throughout the rest of the patient's life. Positive psychotic symptoms may fluctuate during the course of the illness, but negative symptoms, especially primary negative symptoms, and cognitive dysfunction are relatively constant. The negative symptoms of schizophrenia are both primary (associated with the illness) and secondary (due to depression, neuroleptic-induced parkinsonism or acute psychosis). While secondary negative symptoms may be reduced by treating the causative agent, primary negative symptoms are viewed as enduring, persisting between psychotic episodes. Conventional antipsychotics treat the positive symptoms of schizophrenia, but they have little effect on primary negative and cognitive symptoms. Primary negative symptoms are often associated with poor premorbid function, the male sex, and low IQ (Intelligence Quotient). In addition, most studies find that negative symptoms are associated with a poor overall outcome. Several studies, including our own, have suggested that primary negative symptoms are functionally localized to the frontal and parietal cortices. These kinds of data raise the possibility that primary negative symptoms may have a pathophysiological basis distinct from positive psychosis. Cognitive impairment also appears to be a relatively independent aspect of schizophrenia. Impairment may be evident in a subtle form from early childhood, and often precedes the development of psychotic symptoms. Additional impairment accrues with the onset of psychotic illness with little evidence, in the vast majority of cases, of progression over the course of the illness. Cognitive impairment is only modestly related to psychotic symptom severity and type. However, the extent, and perhaps specific types of cognitive impairment, appear to be predictive of functional outcome.