精神分裂症临床高危个体的弥散 MRI 显示细胞外自由水无变化但细胞白质改变。
Altered Cellular White Matter But Not Extracellular Free Water on Diffusion MRI in Individuals at Clinical High Risk for Psychosis.
机构信息
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).
出版信息
Am J Psychiatry. 2019 Oct 1;176(10):820-828. doi: 10.1176/appi.ajp.2019.18091044. Epub 2019 Jun 24.
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) and the volume fraction of extracellular free water (FW).
RESULTS
Significantly lower FA 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 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.
目的
在精神病发作前检测临床高危人群的大脑异常对于追踪病理途径和确定可能阻碍或预防精神病发作的干预策略非常重要。首次精神病发作后，先前已发现细胞和细胞外的白质改变同时发生。作者研究了在经历精神病症状减轻的主要未经药物治疗的临床高危个体人群中，细胞和细胞外改变是否已经存在。
方法
将 50 名处于临床高风险的个体（其中 40 名从未接受过药物治疗）与 50 名健康对照组进行比较，这些对照组在年龄、性别和父母社会经济地位方面与实验组相匹配。使用 3-T 多壳扩散 MRI 数据来估计自由水成像白质测量值，包括细胞组织的各向异性分数（FA）和细胞外自由水的体积分数（FW）。
结果
与健康对照组相比，临床高风险组的 FA 明显较低，但两组之间没有观察到 FW 的统计学显著变化。与前 12 个月的最高 GAF 评分相比，临床高风险组的 FA 越低，与全球功能评估量表（GAF）评分的下降呈显著相关。
结论
细胞而非细胞外改变特征化了临床高风险组，特别是在那些功能下降的患者中。这些细胞变化表明存在早期缺陷，可能反映了发展出减轻的精神病症状的倾向。相比之下，在这个临床高风险样本中没有观察到细胞外改变，这表明先前报道的细胞外异常可能反映了对精神病的急性反应，而这种反应在更接近或在精神病发作时起着更为突出的作用。
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