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

Department of Psychiatry, Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.05). 07/2008; 34(2):468-76. DOI: 10.1038/npp.2008.79
Source: PubMed


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.

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Available from: John A Sweeney, Jan 08, 2014
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    • "These findings suggest differential effects of illness on neural systems supporting the accuracy of saccades guided by internal representations, and differential effects of antipsychotic treatment on these neural systems in the two psychotic disorders. In schizophrenia patients, the specificity of the post-treatment deficit for saccades guided by learned, internal representations of a predictable target's appearance in time and space, and no deficit in accuracy of saccades made in response to sensory input, is a replication of findings in a prior study with an independent sample of antipsychotic-naïve first-episode schizophrenia (Harris et al., 2009). The dose-dependent decline in anticipatory saccade accuracy after treatment suggests that antipsychotic medication may directly alter the integrity of neural systems supporting operations such as spatial learning and memory, response planning or procedural learning. "
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    ABSTRACT: Neurocognitive deficits are associated with most psychotic disorders, but may differ across diagnosis and by treatment status. This ambiguity is partly addressed in longitudinal pre/post treatment studies with first episode patients. Antipsychotic-naïve first-episode schizophrenia patients have shown intact performance on a predictive saccade task that assesses simple motor learning, spatial abilities, and response planning. After antipsychotic treatment, however, schizophrenia patients performing this task show a selective impairment in the accuracy of anticipatory responses, generated from learned internal representations of the task stimulus. This finding is in line with other observations of antipsychotic medication effects on frontostriatal systems, particularly dorsolateral prefrontal cortex. We sought to replicate this provocative finding with an independent sample of antipsychotic-naïve first-episode schizophrenia patients and extend it by including a group of patients with first episode bipolar disorder with psychosis (BDP). Matched healthy controls were also studied in parallel. Schizophrenia patients demonstrated intact performance pretreatment followed by impairment post-treatment for accuracy of anticipatory responses, and worse accuracy was associated with higher antipsychotic dose. BDP patients displayed saccade accuracy deficits before and after treatment and had no correlation of performance and antipsychotic dose. The findings suggest different neural alterations early in the course of each psychotic disorder, and different vulnerabilities to antipsychotic treatment effects between schizophrenia and BDP.
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    • "Beninger et al. (2003) reported that patients receiving first-generation antipsychotics show disrupted feedback-driven learning, which was replicated by Kéri et al. (2005) using another feedbackbased learning task. Harris et al. (2009) found spared procedural learning in drug-naïve patients with schizophrenia , which was disrupted by antipsychotic medications. A plausible explanation may be that strong dopamine receptor antagonists interfere with reward-processing (Pessiglione et al., 2006), which may contribute to deficient feedback processing and procedural learning. "
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    ABSTRACT: Procedural learning is an implicit process in which a behavioral response is refined through repeated performance. Neural systems supporting this cognitive process include specific frontostriatal systems responsible for the preparation and timing of planned motor responses. Evaluating performance on procedural learning tasks can provide unique information about neurodevelopmental disorders in which frontostriatal disturbances have been reported, such as autism. Fifty-two individuals with autism and 54 age-, IQ-, and gender-matched healthy individuals performed an oculomotor serial reaction time task and a sensorimotor control task. Whereas the rate of procedural learning and the precision of planned motor responses were unimpaired in autism, a lateralized alteration in the ability to time predictive responses was observed. Rightward saccadic responses were speeded in individuals with autism relative to healthy control subjects. Speeded rightward predictive saccades suggest atypical functioning of left hemisphere striatal chronometric systems in autism.
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