Department of Psychology, Northwestern University, Evanston, Illinois, USA.
Department of Statistics and Data Science, Northwestern University, Evanston, Illinois, USA.
Hum Brain Mapp. 2024 Feb 1;45(2):e26615. doi: 10.1002/hbm.26615.
Violence exposure is associated with worsening anxiety and depression symptoms among adolescents. Mechanistically, social defeat stress models in mice indicate that violence increases peripherally derived macrophages in threat appraisal regions of the brain, which have been causally linked to anxious behavior. In the present study, we investigate if there is a path connecting violence exposure with internalizing symptom severity through peripheral inflammation and amygdala connectivity. Two hundred and thirty-three adolescents, ages 12-15, from the Chicago area completed clinical assessments, immune assays and neuroimaging. A high-dimensional multimodal mediation model was fit, using violence exposure as the predictor, 12 immune variables as the first set of mediators and 288 amygdala connectivity variables as the second set, and internalizing symptoms as the primary outcome measure. 56.2% of the sample had been exposed to violence in their lifetime. Amygdala-hippocampus connectivity mediated the association between violence exposure and internalizing symptoms ( , ). There was no evidence that inflammation or inflammation and amygdala connectivity in tandem mediated the association. Considering the amygdala and the hippocampus work together to encode, consolidate, and retrieve contextual fear memories, violence exposure may be associated with greater connectivity between the amygdala and the hippocampus because it could be adaptive for the amygdala and the hippocampus to be in greater communication following violence exposure to facilitate evaluation of contextual threat cues. Therefore, chronic elevations of amygdala-hippocampal connectivity may indicate persistent vigilance that leads to internalizing symptoms.
暴力暴露与青少年焦虑和抑郁症状的恶化有关。从机制上讲，小鼠的社会挫败应激模型表明，暴力会增加威胁评估区域中源自外周的巨噬细胞，这些巨噬细胞与焦虑行为有因果关系。在本研究中，我们通过外周炎症和杏仁核连接来研究暴力暴露与内化症状严重程度之间是否存在联系。来自芝加哥地区的 233 名 12-15 岁的青少年完成了临床评估、免疫检测和神经影像学检查。使用暴力暴露作为预测因子，将 12 个免疫变量作为第一组中介，将 288 个杏仁核连接变量作为第二组中介，以内化症状作为主要结果指标，拟合了一个高维多模态中介模型。该样本中有 56.2%的人在其一生中曾遭受过暴力。杏仁核-海马连接介导了暴力暴露与内化症状之间的关联（β=0.15，p=0.003）。没有证据表明炎症或炎症和杏仁核连接同时介导了这种关联。考虑到杏仁核和海马一起工作以编码、巩固和检索情境性恐惧记忆，暴力暴露可能与杏仁核和海马之间更大的连接有关，因为在暴力暴露后，杏仁核和海马之间的更大沟通可能对评估情境性威胁线索是适应性的。因此，杏仁核-海马连接的慢性升高可能表明持续的警惕，从而导致内化症状。
