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Common and distinct neural effects of risperidone and olanzapine during procedural learning in schizophrenia: a randomised longitudinal fMRI study

Kumari, V., Ettinger, U., Lee, S.E. , Deuschl, C., Anilkumar, A.P., Schmechtig, A., Corr, P. J., Ffytche, D.H. & Williams, S. C. R. (2015). Common and distinct neural effects of risperidone and olanzapine during procedural learning in schizophrenia: a randomised longitudinal fMRI study. Psychopharmacology, 232(17), pp. 3135-3147. doi: 10.1007/s00213-015-3959-1

Abstract

Rationale

Most cognitive domains show only minimal improvement following typical or atypical antipsychotic treatments in schizophrenia, and some may even worsen. One domain that may worsen is procedural learning, an implicit memory function relying mainly on the integrity of the fronto-striatal system.

Objectives

We investigated whether switching to atypical antipsychotics would improve procedural learning and task-related neural activation in patients on typical antipsychotics. Furthermore, we explored the differential effects of the atypical antipsychotics risperidone and olanzapine.

Methods

Thirty schizophrenia patients underwent functional magnetic resonance imaging during a 5-min procedural (sequence) learning task on two occasions: at baseline and 7–8 weeks later. Of 30 patients, 10 remained on typical antipsychotics, and 20 were switched randomly in equal numbers to receive either olanzapine (10–20 mg) or risperidone (4–8 mg) for 7–8 weeks.

Results

At baseline, patients (all on typical antipsychotics) showed no procedural learning. At follow-up, patients who remained on typical antipsychotics continued to show a lack of procedural learning, whereas those switched to atypical antipsychotics displayed significant procedural learning (p = 0.001) and increased activation in the superior-middle frontal gyrus, anterior cingulate and striatum (cluster-corrected p < 0.05). These neural effects were present as a linear increase over five successive 30-s blocks of sequenced trials. A switch to either risperidone or olanzapine resulted in comparable performance but with both overlapping and distinct task-related activations.

Conclusions

Atypical antipsychotics restore procedural learning deficits and associated neural activity in schizophrenia. Furthermore, different atypical antipsychotics produce idiosyncratic task-related neural activations, and this specificity may contribute to their differential long-term clinical profiles.

Publication Type: Article
Additional Information: The final publication is available at Springer via http://dx.doi.org/10.1007/s00213-015-3959-1.
Publisher Keywords: Sequence learning, Striatum, Anterior cingulate, Typical antipsychotics, Atypical antipsychotics
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Departments: School of Health & Psychological Sciences > Psychology
SWORD Depositor:
[thumbnail of Kumari%2C%20Ettinger%20et%20al%20%282015%29%20fMRI_PL_Schizophrenia.pdf]
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