Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Psychiatry, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, MA, USA.
Mol Psychiatry. 2021 Sep;26(9):5357-5370. doi: 10.1038/s41380-021-01018-z. Epub 2021 Jan 22.
White matter (WM) abnormalities are repeatedly demonstrated across the schizophrenia time-course. However, our understanding of how demographic and clinical variables interact, influence, or are dependent on WM pathologies is limited. The most well-known barriers to progress are heterogeneous findings due to small sample sizes and the confounding influence of age on WM. The present study leverages access to the harmonized diffusion magnetic-resonance-imaging data and standardized clinical data from 13 international sites (597 schizophrenia patients (SCZ)). Fractional anisotropy (FA) values for all major WM structures in patients were predicted based on FA models estimated from a healthy population (n = 492). We utilized the deviations between predicted and real FA values to answer three essential questions. (1) "Which clinical variables explain WM abnormalities?". (2) "Does the degree of WM abnormalities predict symptom severity?". (3) "Does sex influence any of those relationships?". Regression and mediator analyses revealed that a longer duration-of-illness is associated with more severe WM abnormalities in several tracts. In addition, they demonstrated that a higher antipsychotic medication dose is related to more severe corpus callosum abnormalities. A structural equation model revealed that patients with more WM abnormalities display higher symptom severity. Last, the results exhibited sex-specificity. Males showed a stronger association between duration-of-illness and WM abnormalities. Females presented a stronger association between WM abnormalities and symptom severity, with IQ impacting this relationship. Our findings provide clear evidence for the interaction of demographic, clinical, and behavioral variables with WM pathology in SCZ. Our results also point to the need for longitudinal studies, directly investigating the casualty and sex-specificity of these relationships, as well as the impact of cognitive resiliency on structure-function relationships.
脑白质（WM）异常在精神分裂症的整个病程中反复出现。然而，我们对人口统计学和临床变量如何相互作用、影响或依赖于 WM 病理学的理解是有限的。最著名的进展障碍是由于样本量小和年龄对 WM 的混杂影响而导致的结果不一致。本研究利用了来自 13 个国际站点（597 名精神分裂症患者（SCZ））的协调扩散磁共振成像数据和标准化临床数据的访问权限。根据从健康人群中估计的 FA 模型，预测了患者所有主要 WM 结构的各向异性分数（FA）值（n = 492）。我们利用预测 FA 值和实际 FA 值之间的偏差来回答三个基本问题。（1）“哪些临床变量解释 WM 异常？”。（2）“WM 异常的程度是否预测症状严重程度？”。（3）“性别是否会影响这些关系？”。回归和中介分析表明，病程较长与几个脑区的 WM 异常更严重有关。此外，他们还表明，抗精神病药物剂量越高，与胼胝体异常越严重有关。结构方程模型表明，WM 异常较多的患者症状严重程度较高。最后，结果表现出性别特异性。男性在病程与 WM 异常之间的关联更强。女性在 WM 异常与症状严重程度之间的关联更强，而 IQ 则影响这种关系。我们的研究结果为 SCZ 中人口统计学、临床和行为变量与 WM 病理学的相互作用提供了明确的证据。我们的结果还表明，需要进行纵向研究，直接研究这些关系的因果关系和性别特异性，以及认知弹性对结构-功能关系的影响。
