title: Common and distinct neural effects of risperidone and olanzapine during procedural learning in schizophrenia: a randomised longitudinal fMRI study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Psychology, P078, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK, veena.kumari@kcl.ac.uk.
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ettinger
authors.forename: Seoung Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Christine
authors.initials: C
authors.lastname: Deuschl
authors.forename: Anantha P
authors.initials: AP
authors.lastname: Anilkumar
authors.forename: Anne
authors.initials: A
authors.lastname: Schmechtig
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Corr
authors.forename: Dominic H
authors.initials: DH
authors.lastname: Ffytche
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007858:Learning / Q000187:drug effects*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011597:Psychomotor Performance / Q000187:drug effects; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine