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

Koning, Jeroen; Tenback, Diederik E.; Os, Jim van; Alemán, André; Kahn, René S.; Harten, Peter N. van

doi:10.1093/schbul/sbn146

Cited by 108 publications

(103 citation statements)

References 63 publications

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“…The present results linking pre-treatment EPS to symptom severity in first episode psychosis, to cognitive dysfunction, and to abnormalities of brain structure all support the proposal that similar observations in family members of patients with psychosis represent an endophenotype of the illness [5,6]. Findings concerning the course of extrapyramidal symptoms and the relationships to treatment response indicate the possible importance of thorough assessment for EPS at the entry into early psychosis treatment programs.…”

Section: Discussionsupporting

confidence: 80%

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First episode psychosis with extrapyramidal signs prior to antipsychotic drug treatment

et al. 2011

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Extrapyramidal movement disorders are common in chronic schizophrenia, and may be an intrinsic feature of the illness as well as related to antipsychotic drug treatment. Similar dysfunctions at illness onset may have implications for outcome, and for understanding the mechanisms of illness. The objectives were to examine the clinical correlates of pre-treatment movement disorders at first episode of psychosis, and determine associations with neuropsychological function and striatal structure. Never medicated subjects were recruited from consecutive admissions to Early Psychosis Programs with defined catchment areas in Hong Kong, China, and Halifax, Canada. Standardized clinical, neuropsychological and brain imaging assessments were carried out at baseline and following acute and long term treatment with typical or atypical antipsychotic drugs. At the Hong Kong site, we studied 84 subjects with first episode psychosis (n = 10 with EPS). At the Halifax site, we studied 40 subjects with first episode psychosis (n = 17 with EPS), and 23 healthy comparison subjects. Subjects with movement disorders prior to treatment (EPS+) had higher total PANSS scores at baseline (mean elevation 19.9% Hong Kong, P = 0.016; 14.7% Halifax, P = 0.049). In subjects treated with atypical antipsychotics (all Halifax), EPS+ status at baseline predicted more movement disorders at long term follow up (P = 0.0005). In both cohorts, EPS+ subjects had poorer acute symptomatic treatment response assessed with the PANSS (Hong Kong P = 0.005; Halifax P = 0.017). Neuropsychological impairment related to executive dysfunction appeared greater in a small sample of EPS+ subjects (Hong Kong, effect size 0.26-0.27, P < 0.05). Caudate volumes were 4.5% larger in EPS+ compared with EPS-subjects (Halifax P = 0.042), and correlations between striatal volumes and age were different in the EPS+ group. In conclusion, pre-treatment EPS is present in a substantial minority of subjects with first episode psychosis, appears to persist at long term follow up, and is associated with poorer response of symptoms to treatment. Selective impairment of executive function and striatal enlargement provides evidence of abnormalities of brain function and structure associated with this aspect of early psychosis. schizophrenia, movement disorder, basal ganglia, antipsychotics, cognitive, psychosis Citation:Honer W G, Lang D J, Kopala L C, et al. First episode psychosis with extrapyramidal signs prior to antipsychotic drug treatment.

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Section: Discussionsupporting

confidence: 80%

“…Many of these same signs are described in family members of patients [5,6]. Most endophenotype studies investigate neurological soft signs, that appear to represent signs of developmental deviance [7,8].…”

mentioning

confidence: 94%

First episode psychosis with extrapyramidal signs prior to antipsychotic drug treatment

et al. 2011

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“…A recent meta-analysis calculated an odds ratio of 3.59 for spontaneous dyskinesia in schizophrenia [58]. However, a large negative study (n = 908) of Southeast Asian drug-naïve, first-episode schizophrenia subjects was not included in the meta-analysis [59].…”

Section: Clinical Perspectivesmentioning

confidence: 99%

“…The Caligiuri group [73,74] used a variety of instrumental measures to reappraise spontaneous parkinsonism in schizophrenia, a finding that has later been replicated using clinical rating scales [13,34,35,75,76]. Meta-analytic results demonstrated an odds ratio of 5.32 for spontaneous parkinsonism in never-treated schizophrenia subjects [58]. Parkinsonism of unmedicated first-episode patients was shown to deteriorate with antipsychotic treatment in some patients (28%), while in others, parkinsonism was unchanged (15%) or ameliorated (6%) with treatment [57].…”

Section: Clinical Perspectivesmentioning

confidence: 99%

Motor Symptoms and Schizophrenia

Walther¹,

Strik²

2012

Neuropsychobiology

308

233

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Classical schizophrenia literature reports motor symptoms as characteristic of the disorder. After the introduction of neuroleptic drugs, the existence of genuine motor disorders was challenged. Renewed interest arose as symptoms were found in never-medicated patients. Reports focused on abnormal involuntary movements, parkinsonism, neurological soft signs, catatonia, negative symptoms, or psychomotor slowing. Since these syndromes refer to different concepts, however, the definitions are not congruent and the symptoms overlap. The prevalence rates of motor symptoms in schizophrenia are surprisingly high, and recent studies indicate a possible pathobiology. In particular, the development and maturation of the human motor system appears to be closely linked to the emergence of motor symptoms observed in schizophrenia. Post-mortem and neuroimaging results demonstrated aberrant structure and function of premotor and motor cortices, basal ganglia, thalamus, and the connecting white matter tracts. Animal models have focused on aberrant neurotransmission and genetic contributions. Findings of localized abnormal oligodendrocyte function and myelination point to the special role of the white matter in schizophrenia, and recent studies specifically found an association between motor abnormalities and white matter structure in schizophrenia. This review of the literature supports the idea that motor symptoms are closely related to the neurodevelopmental disturbances of schizophrenia and a distinct syndromal dimension with its own pathophysiology.

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“…16,17 Interestingly, several studies have shown that spontaneous movement disorders, mainly spontaneous dyskinesia, may be present in antipsychotic-naive schizophrenia patients and may represent an intrinsic neuromotor component of this disorder. [18][19][20] If this concept is valid, it is not possible to differentiate between dyskinesia related to the illness of schizophrenia and drug-induced TD.…”

Section: Introductionmentioning

confidence: 99%

Support for association of HSPG2 with tardive dyskinesia in Caucasian populations

Greenbaum¹,

Alkelai²,

Zozulinsky³

et al. 2011

Pharmacogenomics J

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Tardive dyskinesia (TD) is a severe adverse effect of chronic antipsychotic drug treatment. In addition to clinical risk factors, TD susceptibility is influenced by genetic predisposition. Recently, Syu et al. (2010) reported a genome-wide association screening of TD in Japanese schizophrenia patients. The best result was association of single-nucleotide polymorphism (SNP) rs2445142 in the HSPG2 (heparan sulfate proteoglycan 2) gene with TD. In the present study, we report a replication study of the five top Japanese TDassociated SNPs in two Caucasian TD samples. Applying logistic regression and controlling for relevant clinical risk factors, we were able to replicate the association of HSPG2 SNP rs2445142 with TD in a prospective study sample of 179 Americans of European origin by performing a secondary analysis of the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) genome-wide association study data set, and using a perfect proxy surrogate marker (rs878949; P ¼ 0.039). An association of the 'G' risk allele of HSPG2 SNP rs2445142 with TD was also shown in a sample of Jewish Israeli schizophrenia patients (retrospective, cross-sectional design; P ¼ 0.03). Although the associations were only nominally significant, the findings provide further support for the possible involvement of HSPG2 in susceptibility to TD.

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

Abstract: 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.

Cited by 108 publications

References 63 publications

First episode psychosis with extrapyramidal signs prior to antipsychotic drug treatment

First episode psychosis with extrapyramidal signs prior to antipsychotic drug treatment

Motor Symptoms and Schizophrenia

Support for association of HSPG2 with tardive dyskinesia in Caucasian populations

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