BibTex format
@article{Bukala:2026:10.1007/s00213-026-07173-x,
author = {Bukala, BR and Vano, LJ and Carr, R and Cannon, A and Cummings, C and Davies, D and McCutcheon, R and Statton, B and Berry, A and Sedlacik, J and Albrecht, D and Terry-Lorenzo, R and Haubenberger, D and Howes, OD},
doi = {10.1007/s00213-026-07173-x},
journal = {Psychopharmacology (Berl)},
title = {The mechanism underlying tardive dyskinesia: an exploratory test of the dopamine overactivity hypothesis using MRI imaging of midbrain neuromelanin.},
url = {http://dx.doi.org/10.1007/s00213-026-07173-x},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - RATIONALE: Tardive dyskinesia (TD) is a neurological syndrome of involuntary repetitive movements which results from treatment with antipsychotic medication. The pathoetiology of TD is not well understood but a possible mechanism involves dopaminergic overactivity in the nigrostriatal pathway. If this theory is correct, then levels of neuromelanin (a long-term marker of dopaminergic activity) should be higher in people with TD than those without TD. OBJECTIVES: The aim of the study was to test the hypothesis that neuromelanin levels are higher in patients with TD relative to those without TD. METHODS: Data from 27 participants (TD: n = 13; non-TD n = 14) with a diagnosis of schizophrenia, all taking antipsychotic drugs, were used. Neuromelanin was measured in the midbrain via Magnetic Resonance Imaging (MRI) and compared between the groups. Movement symptoms were measured using the Abnormal Involuntary Movement Scale (AIMS), and antipsychotic dose recorded. RESULTS: MRI-measured neuromelanin levels were significantly higher in patients with TD, as compared to those without (mean = 0.223; t(17.27) = 3.817, p = 0.001; g = 1.386, 95% CI=[0.559, 2.213]). This remained significant after controlling for age, sex, substantia nigra/ventral tegmental area volume and antipsychotic dose (ANCOVA: F(1,20) = 12.08, p = 0.0024; adjusted β = 0.0301, 95% CI [0.0120, 0.0481]). The most pronounced difference was seen in the ventral substantia nigra. CONCLUSIONS: The finding of higher midbrain neuromelanin in patients with TD aligns with the dopamine overactivity hypothesis of TD aetiology. It also supports a neurobiological basis for treatment of TD with drugs that target presynaptic dopamine activity, such as VMAT2 inhibitors. Additionally, it identifies the ventral substantia nigra as a key locus. Future longitudinal studies are needed to delineate if do
AU - Bukala,BR
AU - Vano,LJ
AU - Carr,R
AU - Cannon,A
AU - Cummings,C
AU - Davies,D
AU - McCutcheon,R
AU - Statton,B
AU - Berry,A
AU - Sedlacik,J
AU - Albrecht,D
AU - Terry-Lorenzo,R
AU - Haubenberger,D
AU - Howes,OD
DO - 10.1007/s00213-026-07173-x
PY - 2026///
TI - The mechanism underlying tardive dyskinesia: an exploratory test of the dopamine overactivity hypothesis using MRI imaging of midbrain neuromelanin.
T2 - Psychopharmacology (Berl)
UR - http://dx.doi.org/10.1007/s00213-026-07173-x
UR - https://www.ncbi.nlm.nih.gov/pubmed/42809103
ER -