Handedness and the risk of tardive dyskinesia

Previous results from five cross-sectional studies are conflicting about the relationship between hand preference and tardive dyskinesia (TD): two report a greater TD prevalence in left handers, and three report a greater prevalence in right handers. To help resolve these inconsistencies, the handedness-TD association was assessed in the Yale TD Study, a large prospective cohort investigation of outpatients maintained with neuroleptics. A consistent monotonic association was observed between the handedness score and TD incidence (p = 0.009). The estimated rate ratio, comparing left and mixed handers with pure right handers, adjusted for confounders, was 0.25 (95% confidence interval = 0.09, 0.70). The handedness effect (higher TD rate in right handers) was stronger for subjects with fewer negative symptoms, and it was stronger for men than for women. Although the specific biological mechanisms are unclear, these findings may reflect cerebral laterality in the pathophysiology of psychiatric disorders, possibly in combination with asymmetrical action of neuroleptic exposure.