Abstract
ObjectiveFour 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 7 candidate genes (GRIN2B, GRIN2A, HSPG2, DRD3, DRD4, HTR2C, and NQO1).MethodsNaturalistic 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 45 tag SNPs in 7 candidate genes, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders.ResultsVarious tag SNPs reached nominal significance; TD with rs1345423, rs7192557, rs1650420, as well as rs11644461; orofacial dyskinesia with rs7192557, rs1650420, as well as rs4911871; limb truncal dyskinesia with rs1345423, rs7192557, rs1650420, as well as rs11866328; bradykinesia with rs2192970; akathisia with rs324035; and the principal-factor with rs10772715. After controlling for multiple testing, no significant results remained.ConclusionsThe findings suggest that selected tag 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.
Highlights
Soon after the introduction of antipsychotic medication in 1952, movement disorders emerged as a complication of treatment
tardive dyskinesia (TD) and other movement disorders are associated with social stigmatization, physical disabilities and poorer quality of life
It would be helpful if movement disorders could be predicted from a minimal number of genetic susceptibility loci in candidate genes in combination with demographic, clinical or pharmacological data
Summary
Soon after the introduction of antipsychotic medication in 1952, movement disorders emerged as a complication of treatment. TD and other movement disorders are associated with social stigmatization, physical disabilities and poorer quality of life. They play a role in noncompliance and, risk of psychotic relapse [1,2,3]. A central problem in the management of movement disorders is the lack of clear genetic and non-genetic risk factors that would allow for early identification and prevention. It would be helpful if movement disorders could be predicted from a minimal number of genetic susceptibility loci in candidate genes in combination with demographic, clinical or pharmacological data. A recent meta-analysis on the prevalence of dyskinesia and parkinsonism reported spontaneous dyskinesia and parkinsonism in antipsychotic naıve patients with schizophrenia, and a higher prevalence of dyskinesia and parkinsonism in healthy family members of patients with schizophrenia, compared to matched controls [10]
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