Chronic low-grade inflammation is observed across mental disorders and is associated with difficult-to-treat-symptoms of anhedonia and functional brain changes, reflecting a potential transdiagnostic dimension. Previous investigations have focused on distinct illness categories in people with enduring illness, but few have explored inflammatory changes. We sought to identify an inflammatory signal and the associated brain function underlying anhedonia among young people with recent-onset psychosis and recent-onset depression. Resting-state functional magnetic resonance imaging, inflammatory markers, and anhedonia symptoms were collected from 108 (mean [SD] age = 26.2 [6.2] years; female = 50) participants with recent-onset psychosis ( = 53) and recent-onset depression ( = 55) from the European Union/Seventh Framework Programme–funded PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Time series were extracted using the Schaefer atlas, defining 100 cortical regions of interest. Using advanced multimodal machine learning, an inflammatory marker model and a functional connectivity model were developed to classify participants into an anhedonic group or a normal hedonic group. A repeated nested cross-validation model using inflammatory markers classified normal hedonic and anhedonic recent-onset psychosis/recent-onset depression groups with a balanced accuracy of 63.9% and an area under the curve of 0.61. The functional connectivity model produced a balanced accuracy of 55.2% and an area under the curve of 0.57. Anhedonic group assignment was driven by higher levels of interleukin 6, S100B, and interleukin 1 receptor antagonist and lower levels of interferon gamma, in addition to connectivity within the precuneus and posterior cingulate. We identified a potential transdiagnostic anhedonic subtype that was accounted for by an inflammatory profile and functional connectivity. Results have implications for anhedonia as an emerging transdiagnostic target across emerging mental disorders.

中文翻译：

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快感缺失是一种潜在的跨诊断表型，与近期发病的精神健康疾病中的免疫相关变化有关


在精神障碍中观察到慢性低度炎症，并且与难以治疗的快感缺乏症状和功能性大脑变化相关，反映了潜在的跨诊断维度。之前的研究主要集中在患有慢性疾病的人身上的不同疾病类别，但很少探讨炎症变化。我们试图在患有新发精神病和新发抑郁症的年轻人中识别炎症信号和快感缺失背后的相关大脑功能。收集了 108 名患有新发精神病 (= 53) 和新发抑郁症的参与者（平均 [SD] 年龄 = 26.2 [6.2] 岁；女性 = 50）的静息态功能磁共振成像、炎症标志物和快感缺失症状(= 55) 来自欧盟/第七框架计划资助的 PRONIA（早期精神病管理的个性化预后工具）研究。使用 Schaefer 图集提取时间序列，定义 100 个感兴趣的皮质区域。使用先进的多模式机器学习，开发了炎症标记物模型和功能连接模型，将参与者分为快感缺乏组或正常快感组。使用炎症标记物的重复嵌套交叉验证模型将正常享乐型和缺乏快感型新发精神病/新发抑郁症组分类，平衡准确度为 63.9%，曲线下面积为 0.61。功能连接模型的平衡精度为 55.2%，曲线下面积为 0.57。除了楔前叶和后扣带回内的连接性之外，快感缺失组的分配还受到较高水平的白细胞介素 6、S100B 和白细胞介素 1 受体拮抗剂和较低水平的干扰素 γ 的驱动。 我们发现了一种潜在的跨诊断快感缺乏亚型，该亚型是由炎症特征和功能连接引起的。结果对快感缺失作为新兴精神障碍的新兴跨诊断目标具有重要意义。