Department of Psychiatry & Behavioral Sciences, Weill Institute of Neurosciences, University of California, San Francisco, San Francisco, CA, United States.
Department of Psychology, Stanford University, Stanford, CA, United States; College of Medicine, University of Florida, Gainesville, FL, United States.
Brain Behav Immun. 2022 Feb;100:321-331. doi: 10.1016/j.bbi.2021.12.003. Epub 2021 Dec 9.
Adolescent depression is characterized by heightened inflammation and altered connectivity of fronto-cingulate-limbic tracts, including the genu of the corpus callosum (CCG) and the uncinate fasciculus (UF). No studies, however, have yet examined the association between inflammation, measured by peripheral levels of cytokines, and white matter connectivity of fronto-cingulate-limbic tracts in adolescents. Here, 56 depressed adolescents (32 females, 3 non-binary; 16.23 ± 1.28 years) and 19 controls (10 females; 15.72 ± 1.17 years) completed a diffusion-weighted MRI scan at 3 Tesla. We conducted deterministic tractography to segment bilateral corpus callosum (genu and splenium) and UF and computed mean fractional anisotropy (FA) in each tract. A subset of participants (43 depressed and 17 healthy controls) also provided dried blood spot samples from which we assayed interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-ɑ) using a Luminex multiplex array. Depressed participants did not differ from controls in FA of the corpus callosum or UF (all FDR-corrected ps > 0.056) but exhibited higher levels of inflammation than did controls (IL-6: β = 0.91, FDR-corrected p = 0.006; TNF-α: β = 0.76, FDR-corrected p = 0.006). Although diagnostic group did not moderate the associations between inflammatory cytokines and FA in the CCG and UF, across both groups, greater peripheral inflammation was associated with lower FA in the CCG (IL-6: β = -0.38; FDR-corrected p = 0.044; TNF-ɑ: β = -0.41, FDR-corrected p = 0.044). This study is the first to examine associations between peripheral inflammation and white matter microstructure of fronto-cingulate-limbic tracts in depressed and nondepressed adolescents. Future mechanistic studies are needed to confirm our findings; nevertheless, our results suggest that heightened inflammation is an important component of neurophenotypes that are relevant to adolescent depression.
青少年抑郁症的特点是炎症加剧，并且额皮质边缘束的连接发生改变，包括胼胝体膝部（CCG）和钩束（UF）。但是，目前还没有研究检查外周细胞因子水平测量的炎症与青少年额皮质边缘束的白质连接之间的关联。在这里，56 名抑郁青少年（32 名女性，3 名非二进制；16.23±1.28 岁）和 19 名对照者（10 名女性；15.72±1.17 岁）在 3 Tesla 磁共振成像扫描仪上完成了扩散加权磁共振成像扫描。我们进行了确定性束追踪，以分割双侧胼胝体（膝部和压部）和 UF，并计算了每条束的平均分数各向异性（FA）。参与者的一个子集（43 名抑郁参与者和 17 名健康对照者）还提供了干血斑样本，我们使用 Luminex 多重阵列法检测了白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-ɑ）。抑郁组与对照组在胼胝体或 UF 的 FA 上没有差异（所有 FDR 校正 p 值均>0.056），但炎症水平高于对照组（IL-6：β=0.91，FDR 校正 p=0.006；TNF-α：β=0.76，FDR 校正 p=0.006）。尽管诊断组并未调节炎症细胞因子与 CCG 和 UF 中的 FA 之间的关联，但在两组中，外周炎症的增加与 CCG 中的 FA 降低有关（IL-6：β=-0.38；FDR 校正 p=0.044；TNF-ɑ：β=-0.41，FDR 校正 p=0.044）。这项研究是首次检查抑郁和非抑郁青少年外周炎症与额皮质边缘束白质微观结构之间的关联。需要进行未来的机制研究来证实我们的发现；但是，我们的结果表明，炎症加剧是与青少年抑郁症相关的神经表型的重要组成部分。
