Effects of Risperidone on Procedural Learning in Antipsychotic-Naive First-Episode Schizophrenia

Abstract

Studies of procedural learning in medicated schizophrenia patients using predictive saccade paradigms have consistently demonstrated hypometric predictive responses. Findings from antipsychotic-naive schizophrenia patients indicate fewer or no deficits. This pattern of findings suggests that antipsychotic medications might adversely affect frontostriatal systems supporting procedural learning on this task. The accuracy and latency of predictive saccades were assessed in 25 antipsychotic-naive first-episode schizophrenia patients and 22 matched healthy individuals. Patients were retested after 6 weeks of treatment with risperidone. Healthy individuals were reevaluated after a similar time period. The ability to learn to time response initiation in anticipation of target appearance (target prediction) was not impaired in patients before or after treatment. In contrast, although no deficits were evident before treatment initiation, after treatment patients showed a marked decrease in the accuracy of predictive but not sensory-guided responses. The findings from pretreatment testing indicate that procedural learning is a relatively unaffected cognitive domain in antipsychotic-naive first-episode schizophrenia. Although treatment-emergent extrapyramidal symptoms were minimal, these data suggest that D2 antagonism in striatum after risperidone treatment was sufficiently robust to disrupt the generation of planned volitional behavior guided by internalized representations.

Impact of Antipsychotic Treatment on Attention and Motor Learning Systems in First-Episode Schizophrenia

“…53 Such deficits might influence response to a D2 antagonist such that striatal function may be relatively normalized but frontal cortex may shift further into a state of hypofunction via local effects or changes in thalamic drive. Treatment-related DLPFC reduction is consistent with prior studies showing reduced spatial accuracy of predictive saccades after treatment in first-episode schizophrenia patients 12 and in chronically treated patients. 50,54,55 Measurement of saccade accuracy Notes: Two of the significant clusters from the analysis extended over multiple brain structures.…”

“…12 Functional imaging studies have not been conducted to identify the neural substrate of this treatment-emergent abnormality. Prior task-based imaging studies in first-episode patients have found treatment-emergent reductions in DLFPC and striatum activation, 10,22,23 so alterations to striatal and frontal systems may underlie the behavioral changes observed for predictive saccades after antipsychotic treatment.…”

“…Studies of attention and motor learning systems using eye movement tasks are particularly useful in this regard, because the neural circuitry supporting behavioral performance is well-delineated from prior work in humans and nonhuman primates, [15][16][17][18] and behavioral deficits in schizophrenia are well established in laboratory studies. 12,19,20 Automatic visual attentional processes have been examined with prosaccade tasks, in which a visual target unexpectedly relocates, eliciting a shift in attention and gaze. Untreated first-episode schizophrenia patients show abnormally rapid shifts of gaze 19,20 and this abnormality is reduced after antipsychotic treatment.…”

Probabilistic classification and gambling in patients with schizophrenia receiving medication: comparison of risperidone, olanzapine, clozapine and typical antipsychotics

“…The double dissociation between medication type and task impairment makes it difficult to attribute the deficits to schizophrenia. The prospective study by Harris et al (2009) provides strong evidence that learning impairments are caused by antipsychotics. They tested procedural learning in antipsychotic-naïve firstepisode schizophrenia patients and found no impairments.…”

“…Previous studies have shown that learning mirror drawing that relies on the striatum is impaired in schizophrenia patients treated with risperidone (Scherer et al 2004). In a prospective study, Harris et al (2009) found that first-episode drug-naïve patients subsequently treated with risperidone became impaired on a predictive saccade task. Recently, Rémillard et al (2010) reported that risperidone does not impair the same procedural learning tasks as typical antipsychotics.…”