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## Commentary: Kadir et al. Confirm Known Risk Factors, But TD Remains an Unsolved Problem
In this cross-sectional study of 901 chronic schizophrenia inpatients, Kadir and colleagues report a TD prevalence of 36% and identify several associated factors: older age, male sex, lower education, longer illness duration, higher PANSS negative and cognitive scores, and notably, lower levels of all measured metabolic biomarkers (including HDL-cholesterol and ApoB).
While these observations add to the literature, they do not resolve the fundamental, still unsolved problem of tardive dyskinesia: **why TD develops in some patients but not others despite similar antipsychotic exposure, and why it remains irreversible in many cases.**
The inverse relationship between TD and metabolic biomarkers is intriguing, but the cross-sectional design cannot distinguish cause from effect. Lower lipid levels could predate TD, result from TD (e.g., via increased motor activity), or reflect differential prescribing of older antipsychotics. The study does not test mechanisms.
More critically, even with identified risk factors (age, sex, HDL, ApoB, antipsychotic type), prediction at the individual level remains impossible. TD continues to be diagnosed only after it appears, and current treatments, including VMAT2 inhibitors, do not reverse it in most patients.
Thus, Kadir et al. usefully describe correlates, but the core unsolved problem persists: we cannot prevent TD, we cannot predict it reliably, and we cannot cure it. Until prospective, mechanistic studies are conducted, TD will remain an iatrogenic burden without a solution.
link of study：https://www.sciencedirect.com/science/article/abs/pii/S1876201821003336
