Possible Relationship between Tardive Dyskinesia and Gray Matter Volume

There may be a link between tardive dyskinesia and gray matter volume alterations in the brains of patients with schizophrenia, according to a recent study.

A multinational team of investigators assessed levels of gray matter volume in patients with schizophrenia and matched them with healthy controls in order to see if cerebral changes contribute or manifest in tardive dyskinesia.

Long-term antipsychotic treatment is hypothesized as a root cause for tardive dyskinesia; however, tardive dyskinesia can persist after drug withdrawal, wrote the authors on the study, and so they looked elsewhere for its pathogenesis. The team found an alternate hypothesis which suggested that tardive dyskinesia may stem from structural brain changes, and it was this hypothesis that the team set out to test.

The study included 32 patients with schizophrenia and tardive dyskinesia, 31 patients with schizophrenia without tardive dyskinesia, and 32 healthy controls. There were no significant differences among the 3 groups in terms of age, sex, or education. Furthermore, there were no significant differences between the 2 tardive dyskinesia groups in terms of disease duration or antipsychotic use, either, the investigators reported.

All participants underwent standard voxel-based morphometry as an assessment of gray matter volume. The results revealed significant gray matter volume loss in both tardive dyskinesia patient groups compared with the healthy control cohort. This loss was mostly found in the frontal and temporal cortexes, plus the insula, cerebellum, cuneus and lingual gyrus.

Specifically, the cuneus and lingual gyrus gray matter volume decrease seemed to be positively correlated with AIMS scores in the tardive dyskinesia patients, the authors wrote. This particular finding was in contrast with previous studies that looked at gray matter volume reduction in cuneus and lingual gyrus in schizophrenia compared with healthy controls. Those showed a positive correlation between more severe gray matter volume loss in the right superior frontal gyrus with AIMS score.

“It is very difficult to explain these contrasting and paradoxical findings,” the study authors wrote. “Further, previous studies have reported these frontal and visual cortical abnormalities as a characteristic of schizophrenia. Thus, the current findings remain to be confirmed and whether these structural brain changes are specific to tardive dyskinesia remains to be investigated.”

With or without the presence of tardive dyskinesia, according to the results, patients with schizophrenia had significantly decreased gray matter volume in several brain areas compared with the healthy group.

“It is plausible that both dopamine blocking medication and the pathophysiology of schizophrenia itself contribute to tardive dyskinesia,” the study authors wrote. Although second-generation antipsychotics are more widely available now, which can reduce the incidence and severity of tardive dyskinesia, it is still potentially a dangerous side effect of schizophrenia treatment.

“The current results suggest that tardive dyskinesia may be associated with the alterations in gray matter volume that are different from that of schizophrenics without tardive dyskinesia,” the team concluded. “Further studies are needed to validate this finding; [however,] these findings may facilitate new studies on the neural markers of this debilitating condition.”

The study, “Decreased Gray Matter Volume of Cuneus and Lingual Gyrus in Schizophrenia Patients with Tardive Dyskinesia is Associated with Abnormal Involuntary Movement,” was published in Scientific Reports.