Cerebellar motor learning deficits in medicated and medication-free men with recent-onset schizophrenia

Cerebellar motor learning deficits in medicated and medication-free men with recent-onset schizophrenia


J Psychiatry Neurosci 2013; 39(1): E3-E11

Michael Coesmans, MD, PhD;* Christian H. Röder, MD;* Albertine E. Smit, PhD; Sebastiaan K.E. Koekkoek, PhD; Chris I. De Zeeuw, MD, PhD; Maarten A. Frens, PhD; Josef N. van der Geest, PhD

Coesmans, Röder — Department of Psychiatry, Erasmus MC, Rotterdam, the Netherlands; Coesmans, Smit, Koekkoek, De Zeeuw, Frens, van der Geest — the Department of Neuroscience, Erasmus MC, Rotterdam, the Netherlands; Coesmans— Delta Psychiatric Centre, Poortugaal, the Netherlands; De Zeeuw — the Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts & Sciences, Amsterdam, the Netherlands

*Authors contributed equally to this study.


Background: The notion that cerebellar deficits may underlie clinical symptoms in people with schizophrenia is tested by evaluating 2 forms of cerebellar learning in patients with recent-onset schizophrenia. A potential medication effect is evaluated by including patients with or without antipsychotics.

Methods: We assessed saccadic eye movement adaptation and eyeblink conditioning in men with recentonset schizophrenia who were taking antipsychotic medication or who were antipsychotic-free and in age-matched controls.

Results: We included 39 men with schizophrenia (10 who were taking clozapine, 16 who were taking haloperidol and 13 who were antipsychoticfree) and 29 controls in our study. All participants showed significant saccadic adaptation. Adaptation strength did not differ between healthy controls and men with schizophrenia. The speed of saccade adaptation, however, was significantly lower in men with schizophrenia. They showed a significantly lower increase in the number of conditioned eyeblink responses. Over all experiments, no consistent effects of medication were observed. These outcomes did not correlate with age, years of education, psychopathology or dose of anti psychotics.

Limitations: As patients were not randomized for treatment, an influence of confounding variables associated with medication status cannot be excluded. Individual patients also varied along the schizophrenia spectrum despite the relative homogeneity with respect to onset of illness and short usage of medication. Finally, the relatively small number of participants may have concealed effects as a result of insufficient statistical power.

Conclusion: We found several cerebellar learning deficits in men with schizophrenia that we cannot attribute to the use of antipsychotics. Although this finding, combined with the fact that deficits are already present in patients with recent-onset schizophrenia, could suggest that cerebellar impairments are a trait deficit in people with schizophrenia. This should be confirmed in longitudinal studies.

Submitted Oct. 16, 2012; Revised Mar. 31, Apr. 30, May 8, 2013; Accepted May 13, 2013.

Acknowledgements: We thank Dr. N. van Beveren for help with inclusion of patients and Dr. S.A. Kushner for critical reading of the manuscript. We also thank the anonymous reviewers for their critical appraisal of our work. This work was supported by a European Commission (C7: FP7-ITN) grant to C.I. De Zeeuw and M.A. Frens, a Prinses Beatrix Fonds grant to C.I. De Zeeuw and J.N. van der Geest, a TC2N (Interreg) grant to M.A. Frens and J.N. van der Geest, and a ZonMW/Neuras grant to M.A. Frens.

Competing interests: None declared.

Contributors: M. Coesmans, C.H. Röder, C.I. De Zeeuw, M.A. Frens and J.N. van der Geest designed the study. M. Coesmans, A.E. Smit and S.K.E. Koekkoek acquired the data, which M. Coesmans, C.H. Röder, A.E. Smit, S.K.E. Koekkoek, M.A. Frens and J.N. van der Geest analyzed. M. Coesmans, C.H. Röder and J.N. van der Geest wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.120205

Correspondence to: M.A. Frens, Department of Neuroscience, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, the Netherlands; m.frens@erasmusmc.nl