Candidate Gene-Based Association Study of Antipsychotic-Induced Movement Disorders in Long-Stay Psychiatric Patients: A Prospective Study
Open Access
- 15 May 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (5), e36561
- https://doi.org/10.1371/journal.pone.0036561
Abstract
Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 10 candidate genes (PPP1R1B, BDNF, DRD3, DRD2, HTR2A, HTR2C, COMT, MnSOD, CYP1A2, and RGS2). Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 31 SNPs, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders. Various SNPs reached nominal significance: TD and orofacial dyskinesia with rs6265 and rs988748, limb truncal dyskinesia with rs6314, rest tremor with rs6275, rigidity with rs6265 and rs4680, bradykinesia with rs4795390, akathisia with rs4680, tardive dystonia with rs1799732, rs4880 and rs1152746. After controlling for multiple testing, no significant results remained. The findings suggest that selected SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account.This publication has 42 references indexed in Scilit:
- Long-Stay Psychiatric Patients: A Prospective Study Revealing Persistent Antipsychotic-Induced Movement DisorderPLOS ONE, 2011
- Genomewide Association Study of Movement-Related Adverse Antipsychotic EffectsBiological Psychiatry, 2010
- The Dopamine Hypothesis of Schizophrenia: Version III--The Final Common PathwaySchizophrenia Bulletin, 2009
- Invited Commentary: From Genome-Wide Association Studies to Gene-Environment-Wide Interaction Studies--Challenges and OpportunitiesAmerican Journal of Epidemiology, 2008
- Dyskinesia and Parkinsonism in Antipsychotic-Naive Patients With Schizophrenia, First-Degree Relatives and Healthy Controls: A Meta-analysisSchizophrenia Bulletin, 2008
- The ‘Common Disease-Common Variant’ Hypothesis and Familial RisksPLOS ONE, 2008
- Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controlsNature, 2007
- Deconstructing Schizophrenia: An Overview of the Use of Endophenotypes in Order to Understand a Complex DisorderSchizophrenia Bulletin, 2006
- Neuroleptic-induced Movement Disorders: An OverviewPsychiatric Clinics of North America, 2005
- Nithsdale Schizophrenia Surveys 23: movement disordersThe British Journal of Psychiatry, 2002