Sasabayashi Daiki, Itoh Hiroko, Nemoto Kiyotaka, Higuchi Yuko, Akasaki Yukiko, Wickham Alana, Cho Kang Ik K, Pasternak Ofer, Mohandass Dheshan, Zurrin Ryan, Billah Tashrif, Cetin-Karayumak Suheyla, Kobayashi Haruko, Sakamoto Kazumi, Takayanagi Yoichiro, Tsujii Noa, Koike Shinsuke, Hirano Yoji, Noguchi Kyo, Sumiyoshi Tomiki, Suzuki Michio, Takahashi Tsutomu, Kubicki Marek
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Schizophr Bull. 2025 Jun 25. doi: 10.1093/schbul/sbaf089.
Excessive saturated or deficient unsaturated fatty acids and white matter microstructural abnormalities are observed before the psychosis onset. Whereas fatty acids variations are implicated in white matter pathology, conventional Diffusion Tensor Imaging has limitations in disentangling their biological relevance. Free-water imaging provides improved biological specificity to white matter microstructure, such as fractional volume of free-water (FW) and tissue-specific fractional anisotropy (FAt). This study aims to investigate the associations between altered proportion of saturated or unsaturated fatty acids and free-water imaging parameters in prodromal psychosis.
We applied free-water imaging and Tract-Based Spatial Statistics to compare FAt and FW between 78 individuals with at-risk mental state (ARMS) and 129 healthy controls. In a subsample with available blood samples (n = 53 and n = 42, respectively), relationships between fatty acid composition of erythrocyte membrane and FAt or FW were examined alongside clinical and cognitive variables.
Compared to the controls, individuals with ARMS exhibited higher relative concentrations of saturated fatty acids as well as lower FAt and higher FW in multiple association and projection fibers. In the ARMS group, elevated proportion of saturated fatty acids was associated with lower FAt and with positive symptoms and impaired verbal fluency.
The association of saturated fatty acids with FAt in ARMS suggests that fatty acids may influence disrupted white matter microstructure, such as impaired myelin maintenance prior to psychosis onset. Future studies should explore early interventions to mitigate white matter cellular deterioration by optimizing saturated fatty acid levels.
在精神病发作之前，可观察到饱和脂肪酸过量或不饱和脂肪酸不足以及白质微观结构异常。虽然脂肪酸变化与白质病理学有关，但传统的扩散张量成像在厘清其生物学相关性方面存在局限性。自由水成像为白质微观结构提供了更高的生物学特异性，例如自由水分数体积（FW）和组织特异性分数各向异性（FAt）。本研究旨在探讨前驱性精神病中饱和或不饱和脂肪酸比例改变与自由水成像参数之间的关联。
我们应用自由水成像和基于纤维束的空间统计学方法，比较了78名处于高危精神状态（ARMS）的个体与129名健康对照者的FAt和FW。在一个有可用血样的子样本中（分别为n = 53和n = 42），同时考察了红细胞膜脂肪酸组成与FAt或FW之间的关系以及临床和认知变量。
与对照组相比，ARMS个体在多条联合纤维和投射纤维中表现出更高的饱和脂肪酸相对浓度，以及更低的FAt和更高的FW。在ARMS组中，饱和脂肪酸比例升高与更低的FAt、阳性症状以及言语流畅性受损有关。
ARMS中饱和脂肪酸与FAt的关联表明，脂肪酸可能会影响白质微观结构的破坏，比如在精神病发作前髓鞘维持受损。未来的研究应探索早期干预措施，通过优化饱和脂肪酸水平来减轻白质细胞的恶化。
