Profiles of the pharmacologic response of positive and negative symptoms in schizophrenia

Abstract

SummaryThe delineation of the symptoms of schizophrenia into positive and negative types has been an important trend in psychiatric research over the past decade. This approach reflects renewed interests in clinical description and in developing etiologic hypotheses. The responsivity of positive and negative symptoms to neuroleptic and other pharmacotherapies, an issue of considerable clinical and research importance, however, remain in controversy.We have observed that double-blind fluphenazine administration to 19 schizophrenic inpatients who had been maintained free from neuroleptic treatment for an extended period of time resulted in significant decreases in both positive as well as negative symptoms. The time course of symptom change differed, however, and the change in symptoms was not correlated, suggesting that the underlying pathophysiologies of positive and negative symptoms are only partially overlapping. The relative balance between positive and negative symptoms in individual patients, a putative schizophrenia trait characteristic, was found to be significantly altered by neuroleptic treatment, raising questions about the reliability of this classification approach.In longitudinal studies in which plasma levels of the dopamine metabolite, homovanillic acid (HVA), were measured, change in negative symptoms associated with neuroleptic withdrawal and treatment were correlated, respectively, with changes in levels of plasma HVA. These data further support a relationship between negative symptoms and dopaminergic function. In addition to neuroleptic-induced reductions in negative symptoms, the augmentation of neuroleptic antipsychotic effects by the triazolobenzodiazepine, alprazolam, includes improvement in negative and positive symptoms in responsive patients.These data including longitudinal studies of individual patients suggest that negative as well as positive symptoms respond to pharmacologic intervention. The clinical and research implications of these findings are discussed.