Dyskinesia and Parkinsonism in Antipsychotic-Naive Patients With Schizophrenia, First-Degree Relatives and Healthy Controls: A Meta-analysis

Schizophrenia Bulletin vol. 36 no. 4 pp. 723–731, 2010 doi:10.1093/schbul/sbn146 Advance Access publication on November 5, 2008 Dyskinesia and Parkinsonism in Antipsychotic-Naive Patients With Schizophrenia, First-Degree Relatives and Healthy Controls: A Meta-analysis Key words: spontaneous/movement disorders/ vulnerability/family/nonaffective psychosis 2 Psychiatric Center Symfora groep, Amersfoort, The Netherlands; Rudolph Magnus Institute of Neuroscience; 4Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; 5Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands; 6Division of Psychological Medicine, Institute of Psychiatry, London, UK; 7BCN Neuroimaging Center; 8University Medical Center Groningen, University of Groningen, Groningen, The Netherlands 3 Introduction Movement disorders such as dyskinesia and parkinsonism are primarily associated with the use of antipsychotic medication, particularly in patients with schizophrenia.1–3 However, involuntary hyper- and hypokinetic movements have been described in patients with schizophrenia long before the introduction of antipsychotic medication.4–6 This suggests that these abnormal movements may be related to the illness itself rather than just the result of antipsychotic medication. If abnormal movements were related to the disease, one would expect these movement disorders to be present in antipsychoticnaive patients with schizophrenia. However, although numerous studies7–28 examined the presence of these abnormal movements in antipsychotic-naive patients with schizophrenia, only a few have compared the prevalence of these signs with that in a matched healthy control group.7,8,11,12,15,21,24 Interestingly, while the uncontrolled studies (mostly) observed movement disorders in antipsychotic-naive patients,9,10,13,14,16–20,23,25–28 the controlled studies generally did not report significantly more movement disorders in patients than in healthy controls.7,8,11,12,15,24 If dyskinesia and parkinsonism are present in first-degree relatives of patients with schizophrenia, these movement disorders may be related to the (genetic) risk of developing the disease. However, studies comparing the presence of dyskinesia and parkinsonism in healthy relatives and controls21,29–36 generally report inconclusive results. Therefore, we conducted a meta-analysis to systematically compare the prevalences of dyskinesia and parkinsonism in schizophrenia patients and healthy first-degree relatives each with age-matched controls in the same study. Background: Several studies have reported the presence of dyskinesia and parkinsonism in antipsychotic-naive patients with schizophrenia as well as in their first-degree relatives. These movement disorders may therefore form an integral part of the illness and its (genetic) liability. Method: A systematic search was conducted in the Medline, EMBASE, and PsychINFO databases to identify studies reporting on dyskinesia and parkinsonism assessed in antipsychotic-naive patients with schizophrenia (n 5 213) and controls (n 5 242) and separately in nonill first-degree relatives (n 5 395) and controls (n 5 379). Effect sizes were pooled using random-effect models to calculate odds ratios (ORs) to compare the risk of these movement disorders among patients and healthy relatives each with matched controls. Results: Antipsychotic-naive schizophrenia was found to be strongly associated with dyskinesia (OR: 3.59, 95% confidence interval [CI]: 1.53– 8.41) and parkinsonism (OR: 5.32, 95% CI: 1.75–16.23) compared with controls. Dyskinesia and parkinsonism were also significantly more prevalent in healthy firstdegree relatives of patients with schizophrenia as compared with healthy controls (OR: 1.38, 95% CI: 1.06–1.81, and OR: 1.37, 95% CI: 1.05–1.79, respectively).Conclusion: The results suggest that movement disorders, and by inference abnormalities in the nigrostriatal pathway, are not only associated with schizophrenia itself but may also be related to the (genetic) risk of developing the disease. Methods 1 To whom correspondence should be addressed; c/o. Mrs T. van Polanen, Symfora groep, Medisch centrum, PO Box 3051, 3800 DB Amersfoort, The Netherlands; tel: þ31-33-4609568, fax: þ31-334609557, e-mail: . Data Sources The registers of Medline, EMBASE, and PsychINFO were searched without year limits up to January 2008 Ó The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: . 723 Jeroen PF Koning1–3, Diederik E. Tenback2,4, Jim van Os5,6, André Aleman7,8, René S. Kahn3,4, and Peter N. van Harten2,8 J. P. F. Koning et al. 503 studies (literature search) Exclusion of 463 studies -No relevant information 40 studies Antipsychotic-naïve patients and Relatives 19 studies Relatives Exclusion of 16 studies -13, no control group -2, no specification of dyskinesia / parkinsonism -1, case-control study Exclusion of 13 studies -1, no control group -12, no specification of dyskinesia / parkinsonism 6 studies Antipsychotic-naïve patients 4 studies Siblings 6 studies Relatives 1 study Parents & siblings 1 study Parents Fig. 1. Flowchart of Included Studies. using the following keywords: (dyskinesia or parkinsonism or movement disorders) combined with (antipsychotic-naive or treatment-naive or naive and schizophrenia) and separately with (relatives or family members or parents or offspring or children or siblings and schizophrenia). In addition, all relevant references cited in the articles found were also retrieved. This yielded 503 results, of which 40 original studies contained relevant information. As listed in figure 1, of these 40 studies, 12 were included according to our inclusion criteria: (1) examined dyskinesia and/or parkinsonism in antipsychotic-naive patients with schizophrenia or in their healthy first-degree relatives, (2) compared the results with a healthy control group matched for age, and (3) reported sufficient data to obtain an effect size as measured by prevalences or mean scores, SDs, and number of subjects in each group. Of the 29 excluded studies, 16 studies were on antipsychotic-naive patients9,10,13,14,16,17,19,20,22,23,25–28,37,38 of which 13 had no control group,9,10,13,14,16,17,19,20,23,25–28 1 study was a case-control study,22 and 2 studies did not specify for dyskinesia or parkinsonism.37,38 Of the remaining 13 excluded studies on healthy relatives32,34,35,39–48 (7 on offspring, 39,40,42–45,47 4 on parents and siblings,32,34,35,46 1 on siblings,48 and 1 on first- and second-degree relatives41), 12 studies did not specify for dyskinesia or parkinsonism,32,34,35,39,40,42–48 and 1 did not include a control group.41 We had access to the original data of 1 study,29 and 1 author was contacted and provided the information on dyskine (...truncated)