Poletti Sara, Paolini Marco, Ernst Julia, Bollettini Irene, Melloni Elisa, Vai Benedetta, Harrington Yasmin, Bravi Beatrice, Calesella Federico, Lorenzi Cristina, Zanardi Raffaella, Benedetti Francesco
Psychiatry & Clinical Psychobiology, Division of Neuroscience, Scientific Institute IRCCS Ospedale San Raffaele, Milano, Italy.
Vita-Salute San Raffaele University, Milano, Italy.
Brain Behav Immun Health. 2022 Oct 3;26:100529. doi: 10.1016/j.bbih.2022.100529. eCollection 2022 Dec.
Bipolar disorder (BD) and major depressive disorder (MDD) are severe psychiatric illnesses that share among their environmental risk factors the exposure to adverse childhood experiences (ACE). Exposure to ACE has been associated with long-term changes in brain structure and the immune response. In the lasts decades, brain abnormalities including alterations of white matter (WM) microstructure and higher levels of peripheral immune/inflammatory markers have been reported in BD and MDD and an association between inflammation and WM microstructure has been shown. However, differences in these measures have been reported by comparing the two diagnostic groups. The aim of the present study was to investigate the interplay between ACE, inflammation, and WM in BD and MDD. We hypothesize that inflammation will mediate the association between ACE and WM and that this will be different in the two groups. A sample of 200 patients (100 BD, 100 MDD) underwent 3T MRI scan and ACE assessment through Childhood Trauma Questionnaire. A subgroup of 130 patients (75 MDD and 55 BD) underwent blood sampling for the assessment of immune/inflammatory markers. We observed that ACE associated with higher peripheral levels of IL-2, IL-17, bFGF, IFN-γ, TNF-α, CCL3, CCL4, CCL5, and PDGF-BB only in the BD group. Further, higher levels of CCL3 and IL-2 associated with lower FA in BD. ACE were found to differently affect WM microstructure in the two diagnostic groups and to be negatively associated with FA and AD in BD patients. Mediation analyses showed a significant indirect effect of ACE on WM microstructure mediated by IL-2. Our findings suggest that inflammation may mediate the detrimental effect of early experiences on brain structure and different mechanisms underlying brain alterations in BD and MDD.
双相情感障碍（BD）和重度抑郁症（MDD）是严重的精神疾病，在其环境风险因素中都包括童年不良经历（ACE）。暴露于ACE与大脑结构和免疫反应的长期变化有关。在过去几十年中，BD和MDD患者中已报告存在脑异常，包括白质（WM）微观结构改变和外周免疫/炎症标志物水平升高，并且炎症与WM微观结构之间存在关联。然而，通过比较这两个诊断组，已报告了这些指标的差异。本研究的目的是调查BD和MDD中ACE、炎症和WM之间的相互作用。我们假设炎症将介导ACE与WM之间的关联，并且在两组中这种关联会有所不同。200名患者（100名BD患者，100名MDD患者）的样本接受了3T磁共振成像扫描，并通过儿童创伤问卷进行了ACE评估。130名患者（75名MDD患者和55名BD患者）的亚组进行了血液采样，以评估免疫/炎症标志物。我们观察到，仅在BD组中，ACE与外周IL-2、IL-17、碱性成纤维细胞生长因子（bFGF）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、趋化因子配体3（CCL3）、趋化因子配体4（CCL4）、趋化因子配体5（CCL5）和血小板衍生生长因子-BB（PDGF-BB）水平升高有关。此外，BD患者中CCL3和IL-2水平升高与分数各向异性（FA）降低有关。发现ACE在两个诊断组中对WM微观结构的影响不同，并且与BD患者的FA和轴向扩散率（AD）呈负相关。中介分析显示，ACE通过IL-2对WM微观结构产生显著的间接影响。我们的研究结果表明，炎症可能介导早期经历对脑结构的有害影响以及BD和MDD中脑改变的不同潜在机制。
