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

Research output: Contribution to journalArticle

Veena Kumari, Ulrich Ettinger, Seoung Eun Lee, Christine Deuschl, Anantha P Anilkumar, Anne Schmechtig, Philip J Corr, Dominic H Ffytche, Steven C R Williams

Original languageEnglish
Pages (from-to)3135-3147
Number of pages13
JournalPsychopharmacology
Volume232
Issue number17
Early online date19 May 2015
DOIs
StatePublished - Sep 2015

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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.

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