Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mol Psychiatry. 2023 May;28(5):2030-2038. doi: 10.1038/s41380-023-02068-1. Epub 2023 Apr 24.
Studies applying Free Water Imaging have consistently reported significant global increases in extracellular free water (FW) in populations of individuals with early psychosis. However, these published studies focused on homogenous clinical participant groups (e.g., only first episode or chronic), thereby limiting our understanding of the time course of free water elevations across illness stages. Moreover, the relationship between FW and duration of illness has yet to be directly tested. Leveraging our multi-site diffusion magnetic resonance imaging(dMRI) harmonization approach, we analyzed dMRI scans collected by 12 international sites from 441 healthy controls and 434 individuals diagnosed with schizophrenia-spectrum disorders at different illness stages and ages (15-58 years). We characterized the pattern of age-related FW changes by assessing whole brain white matter in individuals with schizophrenia and healthy controls. In individuals with schizophrenia, average whole brain FW was higher than in controls across all ages, with the greatest FW values observed from 15 to 23 years (effect size range = [0.70-0.87]). Following this peak, FW exhibited a monotonic decrease until reaching a minima at the age of 39 years. After 39 years, an attenuated monotonic increase in FW was observed, but with markedly smaller effect sizes when compared to younger patients (effect size range = [0.32-0.43]). Importantly, FW was found to be negatively associated with duration of illness in schizophrenia (p = 0.006), independent of the effects of other clinical and demographic data. In summary, our study finds in a large, age-diverse sample that participants with schizophrenia with a shorter duration of illness showed higher FW values compared to participants with more prolonged illness. Our findings provide further evidence that elevations in the FW are present in individuals with schizophrenia, with the greatest differences in the FW being observed in those at the early stages of the disorder, which might suggest acute extracellular processes.
研究应用游离水成像技术（Free Water Imaging），一直以来都报告称，患有早期精神病的人群中外周游离水（FW）显著增加。然而，这些已发表的研究集中在同质的临床参与者群体（例如，仅首次发作或慢性），从而限制了我们对疾病各阶段 FW 升高的时间过程的理解。此外，FW 与疾病持续时间之间的关系尚未得到直接检验。利用我们的多中心弥散磁共振成像（dMRI）协调方法，我们分析了来自 12 个国际站点的 441 名健康对照者和 434 名处于不同疾病阶段和年龄（15-58 岁）的精神分裂症谱系障碍患者的 dMRI 扫描。我们通过评估精神分裂症患者和健康对照者的全脑白质，来描述与年龄相关的 FW 变化模式。在精神分裂症患者中，全脑 FW 高于所有年龄段的健康对照组，FW 值在 15-23 岁时最高（效应大小范围=[0.70-0.87]）。FW 在达到 39 岁时达到峰值后呈单调下降趋势，直至达到最小值。在 39 岁之后，FW 呈衰减的单调增加趋势，但与年轻患者相比，FW 的效应大小明显较小（效应大小范围=[0.32-0.43]）。重要的是，FW 与精神分裂症患者的病程呈负相关（p=0.006），独立于其他临床和人口统计学数据的影响。总之，我们的研究在一个年龄范围广泛的大样本中发现，病程较短的精神分裂症患者的 FW 值高于病程较长的患者。我们的研究结果进一步证明，FW 升高存在于精神分裂症患者中，FW 的最大差异出现在疾病早期阶段，这可能提示急性细胞外过程。
