Yingying Tang1, Ofer Pasternak1, Marek Kubicki1, Yogesh Rathi1, Tianhong Zhang1, Junjie Wang1, Huijun Li1, Kristen A Woodberry1, Lihua Xu1, Zhenying Qian1, Anni Zhu1, Susan Whitfield-Gabrieli1, Matcheri S Keshavan1, Margaret Niznikiewicz1, William S Stone1, Robert W McCarley1, Martha E Shenton1, Jijun Wang1, Larry J Seidman1. 1. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
Abstract
OBJECTIVE: Detecting brain abnormalities in clinical high-risk populations before the onset of psychosis is important for tracking pathological pathways and for identifying possible intervention strategies that may impede or prevent the onset of psychotic disorders. Co-occurring cellular and extracellular white matter alterations have previously been implicated after a first psychotic episode. The authors investigated whether or not cellular and extracellular alterations are already present in a predominantly medication-naive cohort of clinical high-risk individuals experiencing attenuated psychotic symptoms. METHODS: Fifty individuals at clinical high risk, of whom 40 were never medicated, were compared with 50 healthy control subjects, group-matched for age, gender, and parental socioeconomic status. 3-T multishell diffusion MRI data were obtained to estimate free-water imaging white matter measures, including fractional anisotropy of cellular tissue (FAT) and the volume fraction of extracellular free water (FW). RESULTS: Significantly lower FAT was observed in the clinical high-risk group compared with the healthy control group, but no statistically significant FW alterations were observed between groups. Lower FAT in the clinical high-risk group was significantly associated with a decline in Global Assessment of Functioning Scale (GAF) score compared with highest GAF score in the previous 12 months. CONCLUSIONS: Cellular but not extracellular alterations characterized the clinical high-risk group, especially in those who experienced a decline in functioning. These cellular changes suggest an early deficit that possibly reflects a predisposition to develop attenuated psychotic symptoms. In contrast, extracellular alterations were not observed in this clinical high-risk sample, suggesting that previously reported extracellular abnormalities may reflect an acute response to psychosis, which plays a more prominent role closer to or at onset of psychosis.
OBJECTIVE: Detecting brain abnormalities in clinical high-risk populations before the onset of psychosis is important for tracking pathological pathways and for identifying possible intervention strategies that may impede or prevent the onset of psychotic disorders. Co-occurring cellular and extracellular white matter alterations have previously been implicated after a first psychotic episode. The authors investigated whether or not cellular and extracellular alterations are already present in a predominantly medication-naive cohort of clinical high-risk individuals experiencing attenuated psychotic symptoms. METHODS: Fifty individuals at clinical high risk, of whom 40 were never medicated, were compared with 50 healthy control subjects, group-matched for age, gender, and parental socioeconomic status. 3-T multishell diffusion MRI data were obtained to estimate free-water imaging white matter measures, including fractional anisotropy of cellular tissue (FAT) and the volume fraction of extracellular free water (FW). RESULTS: Significantly lower FAT was observed in the clinical high-risk group compared with the healthy control group, but no statistically significant FW alterations were observed between groups. Lower FAT in the clinical high-risk group was significantly associated with a decline in Global Assessment of Functioning Scale (GAF) score compared with highest GAF score in the previous 12 months. CONCLUSIONS: Cellular but not extracellular alterations characterized the clinical high-risk group, especially in those who experienced a decline in functioning. These cellular changes suggest an early deficit that possibly reflects a predisposition to develop attenuated psychotic symptoms. In contrast, extracellular alterations were not observed in this clinical high-risk sample, suggesting that previously reported extracellular abnormalities may reflect an acute response to psychosis, which plays a more prominent role closer to or at onset of psychosis.
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