Association of tardive dyskinesia with variation in <i>CYP2D6</i> : Is there a role for active metabolites?
Bibliographic record
Abstract
BACKGROUND: The aim of this study was to examine whether there was an association between tardive dyskinesia (TD) and number of functional CYP2D6 genes. METHODS: A Caucasian sample of 70 patients was recruited in 1996-1997 from South London and Maudsley National Health Service (NHS) Foundation Trust, UK. Subjects had a DSM-IIIR diagnosis of schizophrenia and were treated with typical antipsychotics at doses equivalent to at least 100 mg chlorpromazine daily for at least 12 months prior to assessment. All patients were genotyped for CYP2D6 alleles*3-5, *41, and for amplifications of the gene. RESULTS: There were 13 patients with TD. The mean (standard deviation (SD)) years of duration of antipsychotic treatment in TD-positive was 15.8 (7.9) vs TD-negative 11.1 (7.4) (p=0.04). Increased odds of experiencing TD were associated with increased ability to metabolize CYP2D6, as measured by genotypic category (odds ratio (OR)=4.2), increasing duration in treatment (OR=1.0), and having drug-induced Parkinsonism (OR=9.7). DISCUSSION: We found a significant association between CYP2D6 genotypic category and TD with the direction of effect being an increase in the number of functional CYP2D6 genes being associated with an increased risk of TD. This is the first study to examine the association between TD and CYP2D6 in Caucasians with this number of genotypic categories. In the future, metabolomics may be utilized in the discovery of biomarkers and novel drug targets.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".