Botao Zeng1, Babak A Ardekani2, Yingying Tang3, Tianhong Zhang3, Shanshan Zhao3, Huiru Cui3, Xiaoduo Fan4, Kaiming Zhuo3, Chunbo Li5, Yifeng Xu5, Donald C Goff6, Jijun Wang7. 1. Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, PR China; Department of Psychiatry, Qingdao Mental Health Center, Qingdao 266034, PR China. 2. Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA; The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. 3. Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, PR China. 4. Psychotic Disorders Program, UMass Memorial Medical Center/UMass Medical School, Suite 100, 365 Plantation Street, Worcester, MA 01605, USA. 5. Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, PR China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, 200030, PR China. 6. Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA; The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. Electronic address: Donald.Goff@nyumc.org. 7. Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, PR China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, 200030, PR China. Electronic address: jijunwang27@163.com.
Abstract
BACKGROUND: Abnormal white matter integrity has been reported among first episode schizophrenia patients. However, findings on whether it can be reversed by short-term antipsychotic medications are inconsistent. METHOD: Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophrenia patients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics. White matter integrity is measured using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). These measures showing a group difference by Tract-based spatial statistics (TBSS) at baseline were extracted for longitudinal comparisons. RESULTS: At baseline, patients exhibited lower FA, higher MD and higher RD versus controls in forceps, left superior longitudinal fasciculus, inferior fronto-occipital fasciculus, left corticospinal tract, left uncinate fasciculus, left anterior thalamic radiation, and bilateral inferior longitudinal fasciculi. FA values of schizophrenia patients correlated with their negative symptoms (r=-0.412, P=0.002), working memory (r=0.377, P=0.005) and visual learning (r=0.281, P=0.038). The longitudinal changes in DTI indices in these tracts did not differ between patients and controls. However, among the patients the longitudinal changes in FA values in left superior longitudinal fasciculus correlated with the change of positive symptoms (r=-0.560, p=0.004), and the change of processing speed (r=0.469, p=0.018). CONCLUSIONS: White matter deficits were validated in the present study by a relatively large sample of medication naïve and first episode schizophrenia patients. They could be associated with negative symptoms and cognitive impairment, whereas improvement in white matter integrity of left superior longitudinal fasciculus correlated with improvement in psychosis and processing speed. Further examination of treatment-related changes in white matter integrity may provide clues to the mechanism of antipsychotic response and provide a biomarker for clinical studies.
BACKGROUND:Abnormal white matter integrity has been reported among first episode schizophreniapatients. However, findings on whether it can be reversed by short-term antipsychotic medications are inconsistent. METHOD: Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophreniapatients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics. White matter integrity is measured using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). These measures showing a group difference by Tract-based spatial statistics (TBSS) at baseline were extracted for longitudinal comparisons. RESULTS: At baseline, patients exhibited lower FA, higher MD and higher RD versus controls in forceps, left superior longitudinal fasciculus, inferior fronto-occipital fasciculus, left corticospinal tract, left uncinate fasciculus, left anterior thalamic radiation, and bilateral inferior longitudinal fasciculi. FA values of schizophreniapatients correlated with their negative symptoms (r=-0.412, P=0.002), working memory (r=0.377, P=0.005) and visual learning (r=0.281, P=0.038). The longitudinal changes in DTI indices in these tracts did not differ between patients and controls. However, among the patients the longitudinal changes in FA values in left superior longitudinal fasciculus correlated with the change of positive symptoms (r=-0.560, p=0.004), and the change of processing speed (r=0.469, p=0.018). CONCLUSIONS:White matter deficits were validated in the present study by a relatively large sample of medication naïve and first episode schizophreniapatients. They could be associated with negative symptoms and cognitive impairment, whereas improvement in white matter integrity of left superior longitudinal fasciculus correlated with improvement in psychosis and processing speed. Further examination of treatment-related changes in white matter integrity may provide clues to the mechanism of antipsychotic response and provide a biomarker for clinical studies.
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