Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Copenhagen Research Centre for Mental Health (CORE), Copenhagen University Hospital, Denmark.
Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Copenhagen Research Centre for Mental Health (CORE), Copenhagen University Hospital, Denmark.
Schizophr Res. 2021 Nov;237:192-201. doi: 10.1016/j.schres.2021.09.014. Epub 2021 Sep 17.
Growing evidence suggests that subtle white matter (WM) alterations are associated with psychopathology in individuals at ultra-high risk for psychosis (UHR). However, the longitudinal relationship between symptom progression and WM changes over time remains under-explored. Here, we examine associations between changes in clinical symptoms and changes in WM over six months in a large UHR-cohort.
110 UHR-individuals and 59 healthy controls underwent diffusion weighted imaging at baseline and after six months. Group × time effects on fractional anisotropy (FA) were tested globally and in four predefined regions of interest (ROIs) bilaterally using linear modelling with repeated measures. Correlations between the changes in clinical symptoms and FA changes in the ROIs were examined with Pearson's correlation. A partial least squares correlation-technique (PLS-C) explored multivariate associations between patterns of changes in psychopathology, regional FA and additional WM indices.
At baseline, UHR-individuals displayed significantly lower FA globally (p = 0.018; F = 12.274), in right superior longitudinal fasciculus (p = 0.02; Adj R = 0.07) and in left uncinate fasciculus (p = 0.048; Adj R = 0.058) compared to controls (corrected). We identified a group × time interaction in global FA and right superior longitudinal fasciculus, but the finding did not survive multiple comparisons. However, an increase of negative symptoms in UHR-individuals correlated with FA increase in right superior longitudinal fasciculus (p = 0.048, corrected, r = 0.357), and this finding was supported by the multivariate PLS-C.
We found a positive correlation with a moderate effect between change in negative symptoms and FA change over 6 months in right superior longitudinal fasciculus. This link appeared mainly to reflect a subgroup of UHR-individuals, which already at baseline presented as vulnerable.
越来越多的证据表明，在处于精神病超高风险（UHR）的个体中，细微的白质（WM）改变与精神病理学有关。然而，症状进展与 WM 随时间变化的纵向关系仍未得到充分探索。在这里，我们研究了在一个大型 UHR 队列中，六个月内临床症状变化与 WM 变化之间的关系。
110 名 UHR 个体和 59 名健康对照者在基线和 6 个月后进行了弥散张量成像。使用重复测量的线性模型，在全局和四个预设的双侧感兴趣区（ROI）中测试了组×时间对各向异性分数（FA）的影响。使用 Pearson 相关分析检验了 ROI 中临床症状变化与 FA 变化之间的相关性。偏最小二乘相关技术（PLS-C）探索了精神病理学变化模式、区域 FA 和其他 WM 指标之间的多变量关联。
在基线时，与对照组相比（校正），UHR 个体的全脑 FA 显著降低（p=0.018；F=12.274），右侧上纵束（p=0.02；Adj R=0.07）和左侧钩束（p=0.048；Adj R=0.058）也显著降低。我们发现全脑 FA 和右侧上纵束存在组×时间的交互作用，但这一发现没有通过多重比较检验。然而，UHR 个体的阴性症状增加与右侧上纵束的 FA 增加呈正相关（p=0.048，校正，r=0.357），这一发现得到了多元 PLS-C 的支持。
我们发现，在右侧上纵束中，阴性症状变化与 6 个月内 FA 变化之间存在正相关，且具有中等效应。这种联系主要反映了 UHR 个体的一个亚组，他们在基线时已经表现出脆弱性。
