Gray Matter Abnormalities in Schizophrenia Patients with Tardive Dyskinesia: A Magnetic Resonance Imaging Voxel-Based Morphometry Study

Objective: The pathophysiological mechanism of TD remains unknown. All previous studies, using the region-of-interest method, focused on basal ganglion areas, were with inconsistent results. This whole-brain voxel-based morphometry (VBM) study investigate the grey matter abnormality of TD and its correlates with clinical ratings. Method: High resolution T1-weighted brain volumetric MRI from 25 schizophrenia patients with TD (TD group), 25 age-, gender-, and handedness-matched schizophrenia patients without TD (non-TD group), and 25 matched healthy subjects (NC group) were analyzed using a VBM approach. Clinical ratings included the Positive and Negative Symptom Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS). Results: The TD group had significantly smaller total gray matter volumes than the NC group (p = 0.05). Compared to the non-TD group, the TD group had significantly higher PANSS negative (p<0.001), SAS (p<0.001), and AIMS (p<0.001) scores; and smaller bilateral inferior frontal gyrus, which correlated negatively with the PANSS negative scores (r = -0.366, p<0.05); and smaller right superior frontal gyrus, which correlated negatively with AIMS scores (r = -0.399, p<0.001), and PANSS general score (r = -0.338, p<0.05). Limitations: The cross-section design can't separate the gray matter change to TD from the context of the illness of schizophrenia, although TD with more severe clinical psychopathology could be a phenotype. Conclusions: The schizophrenia patients with TD had significantly reduced gray matter, mostly at the bilateral inferior frontal gyrus and the right superior frontal gyrus, which correlated with severity of clinical symptoms and involuntary movement, respectively.