Longitudinal assessment of methylphenidate effects on oral word production and symptoms in first-episode schizophrenia at acute and stabilized phases

Background: Some studies have reported psychotic symptom exacerbation during "pharmacologic challenge" paradigms using dopamine agonists. Few studies, however, have examined the effects of these agonists on neurocognitive functions in patients with schizophrenia. This study assessed the effects of methylphenidate infusion on an oral word production test with demonstrated sensitivity to frontal lobe lesions, and on clinical state. Methods: Patients were tested at two different phases; at the onset of their first-episode of schizophrenia (acute phase), and then again after they had responded to treatment and were clinically stable (stabilization phase). During each phase, patients were tested prior to and following methylphenidate infusion. Symptom clusters (i.e., positive, negative, and disorganization) were formed from SANS and SADS-C (+PD) ratings at each of these four timepoints. Results: Patients produced significantly more words at preinfusion and while stabilized, suggesting that overall, decreased dopamine activity was associated with better word production. Redundant errors (i.e., perseverations of previously mentioned words and production of multiple words with the same roots) increased significantly following infusion in the stabilized phase. Disorganization symptoms increased significantly following infusion, regardless of study phase. Conclusions: These findings are consistent with previous theoretical and empirical findings relating dopamine activity to verbal output, a "redundancy bias" in cognitive control, and exacerbation of disorganization symptoms. (C) 1999 Society of Biological Psychiatry.