White matter abnormalities in schizophrenia patients with tardive dyskinesia: a diffusion tensor image study.
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.


METHODS
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.
Bai
Ya Mei
YM
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Chou
Kun-Hsien
KH
Lin
Ching-Po
CP
Chen
I-Yun
IY
Li
Cheng-Ta
CT
Yang
Kai Chun
KC
Chou
Yuan-Hwa
YH
Su
Tung-Ping
TP
D000328:Adult; D016880:Anisotropy; D014150:Antipsychotic Agents / Q000009:adverse effects; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001931:Brain Mapping; D038524:Diffusion Magnetic Resonance Imaging; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D012565:Schizophrenic Psychology; D013702:Temporal Lobe
D014150:Antipsychotic Agents