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

Background: Some studies have reported psychotic symptom exacerbation durin g "pharmacologic challenge" paradigms using dopamine agonists. Few studies, however, have examined the effects of these agonists on neurocognitive fun ctions in patients with schizophrenia. This study assessed the effects of m ethylphenidate infusion on an oral word production test with demonstrated s ensitivity to frontal lobe lesions, and on clinical state. Methods: Patients were tested at two different phases; at the onset of thei r first-episode of schizophrenia (acute phase), and then again after they h ad responded to treatment and were clinically stable (stabilization phase). During each phase, patients were tested prior to and following methylpheni date infusion. Symptom clusters (i.e., positive, negative, and disorganizat ion) were formed from SANS and SADS-C (+PD) ratings at each of these four t imepoints. Results: Patients produced significantly more words at preinfusion and whil e stabilized, suggesting that overall, decreased dopamine activity was asso ciated with better word production. Redundant errors (i.e., perseverations of previously mentioned words and production of multiple words with the sam e roots) increased significantly following infusion in the stabilized phase . Disorganization symptoms increased significantly following infusion, rega rdless of study phase. Conclusions: These findings are consistent with previous theoretical and em pirical findings relating dopamine activity to verbal output, a "redundancy bias" in cognitive control, and exacerbation of disorganization symptoms. (C) 1999 Society of Biological Psychiatry.