Objective: Tardive dyskinesia (TD) is a severe side effect of antipsychotics. While increasing evidence suggests that damaged brain microcircuitry of white matter (WM) is responsible for the clinical symptoms in schizophrenia, no reports of WM abnormality associated with TD were noted.
Method: Brain white matter abnormalities were investigated among 20 schizophrenia patients with TD (Schizophrenia with TD group), 20 age-, gender-, and handedness-matched schizophrenic patients without TD (Schizophrenia without TD group), and 20 matched healthy subjects with magnetic resonance imaging and diffusion tensor imaging analysis. Voxel-wise analysis was used to compare fractional anisotropy (FA) maps of the white matter following intersubject registration to Talairach space. Clinical ratings included the Positive and Negative Symptoms Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS).
Results: The study subjects were 75% female with average of 40.1+/-9. 8 years. The Schizophrenia with TD group had significantly higher PANSS total scores (p=0.024), PANSS negative score (p=0.001), SAS (p<0.001) and AIMS (p<0.001) scores; and demonstrated more widespread FA decreases than the Schizophrenia without TD group, especially over the inferior frontal gyrus, temporal sublobar extranuclear WM (around the basal ganglion), parietal precuneus gyrus WM (around somatosensory cortex), and medial frontal gyrus WM (around dorsolateral prefrontal cortex). The AIMS (p<0.01) and SAS (p<0.01) score positively correlated with decreased FA over these areas, and PANSS negative score positively correlated with FA decrease over medial frontal gyrus WM (p<0.01).
Conclusions: More widespread abnormality of white matter was noted among schizophrenia patients than those without, especially involved cortico-basal ganglion circuits with clinical symptom correlation of involuntary movements and negative symptoms. Further studies with larger sample size are required to validate the findings.