Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu 610041, China; Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena 07743, Germany; Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China.
The Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Division of Translational Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; The Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA.
J Affect Disord. 2025 Jan 1;368:493-502. doi: 10.1016/j.jad.2024.09.112. Epub 2024 Sep 17.
Elevated inflammation and impaired white matter (WM) microstructure have been observed in bipolar disorder (BD). The link between inflammation, WM integrity, and psychiatric symptoms in BD-II depression (BDII-D) remains unknown. We aimed to define BDII-D subgroups through the interplay of inflammation and WM microstructure, and to explore differences in psychiatric symptoms between subgroups, thus offering insight into elucidating the explanatory measures linked to BDII-D.
WM differences were compared between 146 BDII-D individuals and 151 health controls (HCs) by Tract-Based Spatial Statistics. Partial correlation with multiple comparison corrections was used to explore associations between WM, inflammation, and psychiatric symptoms. The canonical correlation analysis metrics of WM and inflammation followed by k-means clustering were used to define WM microstructural-inflammation subgroups of BDII-D. The differences in clinical profiles were compared between the subgroups.
Compared with HCs, BDII-D showed significant WM alterations in the anterior thalamic radiation (ATR), cingulum, forceps, and inferior fronto-occipital fasciculus. In BDII-D, lower fraction anisotropy (FA) within the right ATR and cingulum were significantly associated with higher interleukin-6, while lower FA in the cingulum and lower axial diffusivity in the forceps major exhibited significant links with higher C-reactive protein. Among the subgroups identified, subgroup II characterized by elevated inflammation and impaired WM integrity displayed greater psychiatric symptoms.
WM alterations are concentrated in emotional neurocircuits and are linked to inflammation in BDII-D. WM-inflammation subgroups exhibit distinct variations in psychiatric symptoms. Thus, WM alterations and inflammation might be an explanatory process in the pathophysiology of BDII-D.
在双相障碍（BD）中观察到炎症升高和白质（WM）微观结构受损。BD-II 抑郁（BDII-D）中炎症、WM 完整性和精神症状之间的联系尚不清楚。我们旨在通过炎症和 WM 微观结构的相互作用来定义 BDII-D 的亚组，并探讨亚组之间精神症状的差异，从而深入了解与 BDII-D 相关的解释措施。
通过基于束的空间统计学比较 146 名 BDII-D 个体和 151 名健康对照（HCs）之间的 WM 差异。使用具有多重比较校正的偏相关来探索 WM、炎症和精神症状之间的关联。WM 和炎症的典型相关分析指标随后进行 k-均值聚类，用于定义 BDII-D 的 WM 微观结构-炎症亚组。比较亚组之间的临床特征差异。
与 HCs 相比，BDII-D 在前丘脑辐射（ATR）、扣带、钳和下额枕额束中显示出明显的 WM 改变。在 BDII-D 中，右侧 ATR 和扣带内的分数各向异性（FA）降低与白细胞介素-6 升高显著相关，而扣带内的 FA 降低和钳状主要部分的轴向弥散率降低与 C-反应蛋白升高显著相关。在所确定的亚组中，以炎症升高和 WM 完整性受损为特征的亚组 II 表现出更大的精神症状。
WM 改变集中在情绪神经回路中，并与 BDII-D 中的炎症有关。WM-炎症亚组在精神症状方面表现出明显的差异。因此，WM 改变和炎症可能是 BDII-D 病理生理学的一个解释过程。
