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 10 candidate genes (PPP1R1B, BDNF, DRD3, DRD2, HTR2A, HTR2C, COMT, MnSOD, CYP1A2, and RGS2).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 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.ResultsVarious 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.ConclusionsThe 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.
Highlights
Antipsychotics are the central pillar in the treatment of psychotic disorder
Antipsychotic-induced movement disorders [4,5] can be classified, on the one hand, into acute syndromes, that appear within hours/days or weeks after initiating antipsychotic treatment or increasing the antipsychotic dose, e.g. parkinsonism and akathisia, and, on the other hand, tardive syndromes, that develop after months or years of treatment with antipsychotics such as tardive dyskinesia (TD) and tardive dystonia
Given that combinations of acute and chronic movement disorders occur in patients undergoing longterm treatment with antipsychotics, prediction models should include both syndromes, i.e., the four major types of movement disorders (TD, parkinsonism, akathisia and tardive dystonia)
Summary
Antipsychotics are the central pillar in the treatment of psychotic disorder These agents can induce movement disorders, which are associated with social stigmatization, physical disabilities and poorer quality of life. They contribute to noncompliance, which results in an increased risk of psychotic relapse [1,2,3]. The term ‘tardive’ (delayed) was introduced to emphasize the late-onset types of movement disorders occurring during antipsychotic use. Given that combinations of acute and chronic movement disorders occur in patients undergoing longterm treatment with antipsychotics, prediction models should include both syndromes, i.e., the four major types of movement disorders (TD, parkinsonism, akathisia and tardive dystonia)
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