Altered Cellular White Matter But Not Extracellular Free Water on Diffusion MRI in Individuals at Clinical High Risk for Psychosis

Yingying Tang; Ofer Pasternak; Marek Kubicki; Yogesh Rathi; Tianhong Zhang; Junjie Wang; Huijun Li; Kristen A Woodberry; Lihua Xu; Zhenying Qian; Anni Zhu; Susan Whitfield-Gabrieli; Matcheri S Keshavan; Margaret Niznikiewicz; William S Stone; Robert W McCarley; Martha E Shenton; Jijun Wang; Larry J Seidman

doi:10.1176/appi.ajp.2019.18091044

Altered Cellular White Matter But Not Extracellular Free Water on Diffusion MRI in Individuals at Clinical High Risk for Psychosis

Am J Psychiatry. 2019 Oct 1;176(10):820-828. doi: 10.1176/appi.ajp.2019.18091044. Epub 2019 Jun 24.

Authors

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

Affiliation

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 (FA_T) and the volume fraction of extracellular free water (FW).

Results: Significantly lower FA_T 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 FA_T 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.

Keywords: Clinical High-Risk; Diffusion Tensor Imaging; Free Water; Neurodevelopment; Psychosis; White Matter.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging*
Brain / pathology
Case-Control Studies
Diffusion Magnetic Resonance Imaging
Extracellular Space / metabolism
Female
Humans
Male
Neuroimaging
Psychotic Disorders / diagnostic imaging*
Psychotic Disorders / pathology
Risk Factors
Water
White Matter / diagnostic imaging*
White Matter / pathology
Young Adult

Substances

Water

Abstract

Publication types

MeSH terms

Substances

Grants and funding