BACKGROUND Depression is frequently associated with multiple sclerosis (MS). However, the biological background underlying such association is poorly understood. OBJECTIVE Investigating the functional connections of neurotransmitter-related brainstem nuclei, along with their relationship with white matter (WM) microstructure, in MS patients with depressive symptomatology (MS-D) and without depressive symptomatology (MS-nD). METHODS Combined resting-state functional magnetic resonance imaging (fMRI) and diffusion-weighted MRI (dMRI) study on 50 MS patients, including 19 MS-D and 31 MS-nD patients, along with 37 healthy controls (HC). Main analyses performed are (1) comparison between groups of raphe nuclei (RN)-related functional connectivity (FC); (2) correlation between RN-related FC and whole brain dMRI-derived fractional anisotropy (FA) map; and (3) comparison between groups of FA in the RN-related WM area. RESULTS (1) RN-related FC was reduced in MS-D when compared to MS-nD and HC; (2) RN-related FC positively correlated with FA in a WM cluster mainly encompassing thalamic/basal ganglia regions, including the fornix; and (3) FA in such WM area was reduced in MS-D. CONCLUSION Depressive symptomatology in MS is specifically associated to a functional disconnection of neurotransmitter-related nuclei, which in turn may be traced to a distinct spatial pattern of WM alterations mainly involving the limbic network.

中文翻译：

---

抑郁症与多发性硬化症中神经递质相关核的断开有关

背景抑郁症经常与多发性硬化症(MS)有关。然而，人们对这种关联背后的生物学背景知之甚少。目的研究神经递质相关脑干核的功能连接，以及它们与白质 (WM) 微观结构的关系，在患有抑郁症状 (MS-D) 和无抑郁症状 (MS-nD) 的 MS 患者中。方法 对 50 名 MS 患者（包括 19 名 MS-D 和 31 名 MS-nD 患者）以及 37 名健康对照（HC）进行静息态功能磁共振成像 (fMRI) 和弥散加权 MRI (dMRI) 联合研究。进行的主要分析是 (1) 中缝核 (RN) 相关功能连接 (FC) 组之间的比较；(2) RN相关FC与全脑dMRI衍生的分数各向异性(FA)图的相关性；(3) RN 相关 WM 区域中 FA 组之间的比较。结果 (1) 与 MS-nD 和 HC 相比，MS-D 中 RN 相关的 FC 减少；(2) RN 相关 FC 与 WM 集群中的 FA 正相关，主要包括丘脑/基底神经节区域，包括穹窿；(3) 在 MS-D 中，此类 WM 区域的 FA 减少。结论 MS 的抑郁症状与神经递质相关核的功能性断开特别相关，这反过来又可以追溯到 WM 改变的独特空间模式，主要涉及边缘网络。(3) 在 MS-D 中，此类 WM 区域的 FA 减少。结论 MS 中的抑郁症状与神经递质相关核的功能性断开特别相关，这反过来又可以追溯到 WM 改变的独特空间模式，主要涉及边缘网络。(3) 在 MS-D 中，此类 WM 区域的 FA 减少。结论 MS 中的抑郁症状与神经递质相关核的功能性断开特别相关，这反过来又可以追溯到 WM 改变的独特空间模式，主要涉及边缘网络。