Stolfi Fabiola, Brasso Claudio, Raineri Davide, Landra Virginia, Mazzucca Camilla Barbero, Ghazanfar Ali, Scotti Lorenza, Sinella Riccardo, Villari Vincenzo, Cappellano Giuseppe, Rocca Paola, Chiocchetti Annalisa
Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases-IRCAD, University of Eastern Piedmont, 28100, Novara, Italy.
Center for Translational Research on Autoimmune and Allergic Diseases, University of Eastern Piedmont, 28100, Novara, Italy.
Brain Behav Immun Health. 2024 Dec 30;43:100942. doi: 10.1016/j.bbih.2024.100942. eCollection 2025 Feb.
Major Depressive Disorder (MDD) is a widespread psychiatric condition impacting social and occupational functioning, making it a leading cause of disability. The diagnosis of MDD remains clinical, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, as biomarkers have not yet been validated for diagnostic purposes or as predictors of treatment response. Traditional treatment strategies often follow a one-size-fits-all approach obtaining suboptimal outcomes for many patients who fail to experience response or recovery. Several studies have reported an association between MDD and immune system dysregulation, but few have focused on the deep characterization of circulating cells, during the acute phase of MDD. This work aimed at immunophenotyping peripheral blood cells in the relapse phase of the disorder, to identify relevant cell populations for clinical monitoring of patients. Multiparametric analysis was performed on the peripheral blood of 60 MDD patients using flow cytometry to identify lymphocytes (naïve/effector, memory, regulatory) and myeloid cells (dendritic cells, monocytes). We studied the associations between immunophenotype and depressive symptoms, social and working functioning, and subjective quality of life during the acute phase and after three months of treatment. Multivariate analysis showed that CD4 terminally differentiated effector memory (TEMRA) were associated with more depressive symptoms with a particular emphasis on anhedonic features and worse social and working functioning and quality of life. CD8 TEMRA were associated with those depressive symptoms related to hopelessness. Conversely, ICOS + Tregs were associated with low-intensity suicidal ideation, suggestive of a protective role. Baseline T CD4 effector memory (EM) was a negative predictor of reduction of depressive symptoms after three months of treatment, whilst plasmacytoid dendritic cells (pDC) were predicting reduction of hopelessness. These results confirm the involvement of the immune system in MDD and demonstrate the existence of immunological signatures associated with the severity of major depressive episodes and treatment response that could guide clinical monitoring and future personalized therapies.
重度抑郁症（MDD）是一种广泛存在的精神疾病，会影响社会和职业功能，是导致残疾的主要原因。MDD的诊断仍然基于临床，依据《精神疾病诊断与统计手册》（DSM）-5标准，因为生物标志物尚未被验证用于诊断目的或作为治疗反应的预测指标。传统的治疗策略往往采用一刀切的方法，对于许多未能产生反应或康复的患者来说，效果并不理想。几项研究报告了MDD与免疫系统失调之间的关联，但很少有研究关注MDD急性期循环细胞的深入特征。这项工作旨在对该疾病复发期的外周血细胞进行免疫表型分析，以确定用于患者临床监测的相关细胞群体。使用流式细胞术对60例MDD患者的外周血进行多参数分析，以识别淋巴细胞（幼稚/效应细胞、记忆细胞、调节性细胞）和髓系细胞（树突状细胞、单核细胞）。我们研究了免疫表型与急性期及治疗三个月后的抑郁症状、社会和工作功能以及主观生活质量之间的关联。多变量分析表明，CD4终末分化效应记忆（TEMRA）细胞与更多的抑郁症状相关，尤其侧重于快感缺失特征以及更差的社会和工作功能及生活质量。CD8 TEMRA细胞与与绝望相关的抑郁症状有关。相反，诱导共刺激分子（ICOS）+调节性T细胞（Tregs）与低强度自杀观念相关，提示具有保护作用。基线T CD4效应记忆（EM）细胞是治疗三个月后抑郁症状减轻的负预测指标，而浆细胞样树突状细胞（pDC）则预测绝望情绪的减轻。这些结果证实了免疫系统参与MDD，并证明存在与重度抑郁发作的严重程度和治疗反应相关的免疫特征，这些特征可指导临床监测和未来的个性化治疗。
