Cao Yuan, Lizano Paulo, Deng Gaoju, Sun Huan, Zhou Xiaoqin, Xie Hongsheng, Zhan Yaru, Mu Jingshi, Long Xipeng, Xiao Hongqi, Liu Shiyu, Gong Qiyong, Qiu Changjian, Jia Zhiyun
Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China.
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
Psychiatry Clin Neurosci. 2023 Nov;77(11):613-621. doi: 10.1111/pcn.13585. Epub 2023 Sep 8.
Elevated inflammation and larger choroid plexus (ChP) volume has been previously identified in mood disorders. Connections between inflammation, ChP, and clinical symptoms in bipolar II depression (BDII-D) are unclear. Data-driven clustering based on neuroanatomical phenotypes may help to elucidate neurobiological associations in BDII-D.
Inflammatory cytokines, clinical symptoms, and neuroanatomical features were assessed in 150 BDII-D patients. Sixty-eight cortical surface area (SA) and 19 subcortical volumes were extracted using FreeSurfer. The ChP volume was segmented manually using 3D Slicer. Regularized canonical correlation analysis was used to identify significantly correlated components between cortical SA and subcortical volumes (excluding the ChP), followed by k-means clustering to define brain-derived subgroups of BDII-D. Low-grade inflammation was derived by averaging the standardized z scores of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), which were computed to create a composite z-value score. Partial Pearson correlations followed by multiple comparison correction were conducted to explore associations between inflammation, clinical symptoms, and ChP volume.
Subgroup I demonstrated smaller subcortical volume and cortical SA, higher inflammation, and larger ChP volume compared with subgroup II. Greater ChP volume was associated with a higher low-grade inflammation (mean r = 0.289, q = 0.003), CRP (mean r = 0.249, q = 0.007), IL-6 (left r = 0.200, q = 0.03), and TNF-α (right r = 0.226, q = 0.01), while greater IL-1β was significantly associated with severe depressive symptoms in BDII-D (r = 0.218, q = 0.045).
Neuroanatomically-derived subgroups of BDII-D differed in their inflammation levels and ChP volume. These findings suggest an important role of elevated peripheral inflammation and larger ChP in BDII-D.
先前已在情绪障碍中发现炎症升高和脉络丛（ChP）体积增大。双相II型抑郁症（BDII-D）中炎症、脉络丛与临床症状之间的联系尚不清楚。基于神经解剖学表型的数据驱动聚类可能有助于阐明BDII-D中的神经生物学关联。
对150例BDII-D患者评估炎症细胞因子、临床症状和神经解剖学特征。使用FreeSurfer提取68个皮质表面积（SA）和19个皮质下体积。使用3D Slicer手动分割脉络丛体积。采用正则化典型相关分析确定皮质SA与皮质下体积（不包括脉络丛）之间的显著相关成分，然后进行k均值聚类以定义BDII-D的脑源性亚组。通过对白介素（IL）-6、IL-1β和肿瘤坏死因子-α（TNF-α）的标准化z评分求平均值得出低度炎症，计算这些评分以创建一个复合z值分数。进行偏皮尔逊相关性分析并进行多重比较校正，以探讨炎症、临床症状与脉络丛体积之间的关联。
与亚组II相比，亚组I的皮质下体积和皮质SA较小，炎症较高，脉络丛体积较大。脉络丛体积越大，与较高的低度炎症（平均r = 0.289，q = 0.003）、CRP（平均r = 0.249，q = 0.007）、IL-6（左侧r = 0.200，q = 0.03）和TNF-α（右侧r = 0.226，q = 0.01）相关，而较高的IL-1β与BDII-D中的严重抑郁症状显著相关（r = 0.218，q = 0.045）。
BDII-D的神经解剖学亚组在炎症水平和脉络丛体积方面存在差异。这些发现表明外周炎症升高和脉络丛体积增大在BDII-D中起重要作用。
