Procedural Learning in Schizophrenia Can Reflect the Pharmacologic Properties of the Antipsychotic Treatments

Background:Conventional and atypical antipsychotics have different affinities for D2 receptors, and these receptors are principally located in the striatum. Given that this cerebral structure was previously found to play a major role in procedural learning, the antipsychotic treatment in schizophrenia may be determinant for the procedural learning profile of these patients. Objective:The current study was aimed at verifying whether procedural learning differs in patients with schizophrenia treated with conventional antipsychotics and patients treated with atypical antipsychotics. Method:Forty-five patients with schizophrenia were divided into 3 different groups according to their pharmacologic treatment: (1) haloperidol, a classical neuroleptic with high D2 receptor affinity; (2) clozapine, an atypical neuroleptic with practically no D2 receptor affinity; and (3) risperidone, an atypical neuroleptic that nevertheless shows high D2 receptor affinity. Patients were compared to 35 control subjects on a visuomotor procedural learning task (mirror drawing). Results:All patients were able to learn the task. However, those treated with haloperidol showed some degree of learning impairment, while those treated with clozapine or risperidone did not show this impairment. In addition, performance per se, regardless of the learning, was found to be affected in the haloperidol and risperidone, but not in the clozapine groups. Conclusion:Procedural learning in schizophrenia may be differentially affected, depending on the pharmacologic profiles of the antipsychotics used for the treatment of this illness.

[1]  Julie Kreyenbuhl,et al.  Practice guideline for the treatment of patients with schizophrenia , 1997 .

[2]  Isabelle Rouleau,et al.  Frontal lesions impair the attentional control of movements during motor learning , 1999, Neuropsychologia.

[3]  J. Saint-Cyr,et al.  Procedural learning and neostriatal dysfunction in man. , 1988, Brain : a journal of neurology.

[4]  S. Marder,et al.  Risperidone versus haloperidol on secondary memory: can newer medications aid learning? , 1999, Schizophrenia bulletin.

[5]  B. Bunney,et al.  Typical and atypical neuroleptics: differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  J. Addington,et al.  Neurocognitive and social functioning in schizophrenia. , 1999, Schizophrenia bulletin.

[7]  Eric Granholm,et al.  Preliminary associations between motor procedural learning, basal ganglia T2 relaxation times, and tardive dyskinesia in schizophrenia , 1993, Psychiatry Research: Neuroimaging.

[8]  E. El-Fakahany,et al.  Clozapine interaction with the M2 and M4 subtypes of muscarinic receptors. , 1999, European journal of pharmacology.

[9]  Lewis A. Opler,et al.  Reliability and validity of the positive and negative syndrome scale for schizophrenics , 1988, Psychiatry Research.

[10]  A. Grace The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia. , 1992, Journal of neural transmission. Supplementum.

[11]  Christer Halldin,et al.  5-HT2 and D2 dopamine receptor occupancy in the living human brain , 1993, Psychopharmacology.

[12]  Canadian Cognition and Outcome Study Group Neuropsychological change in early phase schizophrenia over twelve months of treatment with olanzapine, risperidone, or haloperidol , 1998, Schizophrenia Research.

[13]  Alexander L. Miller,et al.  The functional significance of symptomatology and cognitive function in schizophrenia , 1997, Schizophrenia Research.

[14]  S. Deutsch,et al.  Impaired motor skill learning in schizophrenia: implications for corticostriatal dysfunction , 1996, Biological Psychiatry.

[15]  J. Lieberman,et al.  The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. , 1999, Schizophrenia bulletin.

[16]  R. Heinrichs,et al.  Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. , 1998, Neuropsychology.

[17]  E. Stip,et al.  Differential Effects of D2- and D4-Blocking Neuroleptics on the Procedural Learning of Schizophrenic Patients , 1996, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[18]  S. Kapur,et al.  Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. , 1999, The American journal of psychiatry.

[19]  M. Green,et al.  Procedural learning in schizophrenia: evidence from serial reaction time. , 1997, Cognitive neuropsychiatry.

[20]  P. Rosenzweig,et al.  Effects of haloperidol and amisulpride on motor and cognitive skill learning in healthy volunteers , 1997, Psychopharmacology.

[21]  S. Kapur,et al.  D2 and 5-HT2 receptor effects of antipsychotics: bridging basic and clinical findings using PET. , 1999, The Journal of clinical psychiatry.

[22]  O. Blin A Comparative Review of New Antipsychotics , 1999, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[23]  Richard S. J. Frackowiak,et al.  Anatomy of motor learning. I. Frontal cortex and attention to action. , 1997, Journal of neurophysiology.

[24]  N. Lassen,et al.  Altered modulation of prefrontal and subcortical brain activity in newly diagnosed schizophrenia and schizophreniform disorder. A regional cerebral blood flow study. , 1991, Archives of general psychiatry.

[25]  A. Cools,et al.  The acetylcholine-dopamine balance in the basal ganglia of rhesus monkeys and its role in dynamic, dystonic, dyskinetic, and epileptoid motor activities , 2005, Journal of Neural Transmission.

[26]  A. Scheibel,et al.  A neurohistological correlate of schizophrenia. , 1984, Biological psychiatry.

[27]  E. Marder,et al.  Procedural memory in Parkinson's disease: impaired motor but not visuoperceptual learning. , 1990, Journal of clinical and experimental neuropsychology.

[28]  G. Chouinard,et al.  Factors related to tardive dyskinesia. , 1979, The American journal of psychiatry.

[29]  Alan A. Wilson,et al.  The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study. , 1995, Life sciences.

[30]  R. Gur,et al.  Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. , 1998, The American journal of psychiatry.

[31]  J. Danion,et al.  Effects of chlorpromazine and lorazepam on explicit memory, repetition priming and cognitive skill learning in healthy volunteers , 2005, Psychopharmacology.

[32]  M. Nissen,et al.  Procedural learning is impaired in Huntington's disease: Evidence from the serial reaction time task , 1991, Neuropsychologia.

[33]  J. Danion,et al.  Explicit memory, repetition priming and cognitive skill learning in schizophrenia , 1994, Schizophrenia Research.

[34]  S. Kapur,et al.  A new framework for investigating antipsychotic action in humans: lessons from PET imaging , 1998, Molecular Psychiatry.

[35]  T. Goldberg,et al.  Assessment of procedural learning and problem solving in schizophrenic patients by Tower of Hanoi type tasks. , 1990, The Journal of neuropsychiatry and clinical neurosciences.

[36]  G. Sedvall,et al.  Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. , 1992, Archives of general psychiatry.

[37]  Karl J. Friston,et al.  Functional anatomy of human procedural learning determined with regional cerebral blood flow and PET , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  N C Andreasen,et al.  Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London. , 1992, Archives of general psychiatry.

[39]  E. Stip,et al.  Procedural learning in schizophrenia: further consideration on the deleterious effect of neuroleptics. , 2000, Brain and cognition.

[40]  Richard S. J. Frackowiak,et al.  Anatomy of motor learning. II. Subcortical structures and learning by trial and error. , 1997, Journal of neurophysiology.

[41]  A. Baddeley,et al.  Memory in schizophrenia: What is impaired and what is preserved? , 1993, Neuropsychologia.

[42]  E. Stip Novel antipsychotics: issues and controversies. Typicality of atypical antipsychotics. , 2000, Journal of psychiatry & neuroscience : JPN.

[43]  J. Lieberman,et al.  The Prevalence of Acute Extrapyramidal Signs and Symptoms in Patients Treated With Clozapine, Risperidone, and Conventional Antipsychotics , 1998 .

[44]  J. Danion,et al.  Cognitive skill learning and schizophrenia: implications for cognitive remediation. , 1998, Neuropsychology.

[45]  A. L. Wolff,et al.  Motor deficits and schizophrenia: the evidence from neuroleptic-naïve patients and populations at risk. , 1999, Journal of psychiatry & neuroscience : JPN.

[46]  H. Meltzer New insights into schizophrenia through atypical antipsychotic drugs *1Comments on ?the current status of the dopamine hypothesis of schizophrenia? , 1988 .

[47]  A Labelle,et al.  Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. The Canadian Collaborative Group for research in schizophrenia. , 2000, Archives of general psychiatry.