Keding Taylor J, Russell Justin D, Zhu Xiaojin, He Quanfa, Li James J, Herringa Ryan J
Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin; Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Department of Psychology, Yale University, New Haven, Connecticut.
Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 May;10(5):450-462. doi: 10.1016/j.bpsc.2024.08.003. Epub 2024 Sep 7.
Violence exposure during childhood and adolescence is associated with increased prevalence and severity of psychopathology. Neurobiological correlates suggest that abnormal maturation of emotion-related brain circuitry, such as the amygdala-prefrontal cortex (PFC) circuit, may underlie the development of psychiatric symptoms after exposure. However, it remains unclear how amygdala-PFC circuit maturation is related to psychiatric risk in the context of violence.
In this study, we analyzed individual differences in amygdala-PFC circuit maturity using data collected from the PNC (Philadelphia Neurodevelopmental Cohort) (n = 1133 youths). Neurodevelopment models of amygdala-PFC resting-state functional connectivity were built using deep learning and trained to predict chronological age in typically developing youths (not violence exposed and without a psychiatric diagnosis). Using the brain age gap estimate, an index of relative circuit maturation, patterns of atypical neurodevelopment were investigated.
Violence exposure was associated with delayed maturation of basolateral amygdala (BLA)-PFC circuits, driven by increased BLA-medial orbitofrontal cortex functional connectivity. In contrast, increased psychiatric symptoms were associated with advanced maturation of BLA-PFC functional connectivity, driven by decreased BLA-dorsolateral PFC functional connectivity.
Delayed frontoamygdala maturation after exposure to violence suggests atypical, but adaptive, development of threat appraisal processes, potentially reflecting a greater threat generalization characteristic of younger children. Advanced circuit maturation with increasing symptoms suggests divergent neurodevelopmental mechanisms underlying illness after emotion circuits have adapted to adversity, exacerbated by preexisting vulnerabilities to early maturation. Disentangling the effects of adversity and psychopathology on neurodevelopment is crucial for helping youths recover from violence and preventing illness from continuing into adulthood.
儿童期和青少年期遭受暴力与精神病理学患病率和严重程度的增加有关。神经生物学相关性表明，与情绪相关的大脑回路（如杏仁核 - 前额叶皮质（PFC）回路）的异常成熟可能是暴露后精神症状发展的基础。然而，在暴力背景下，杏仁核 - PFC回路成熟与精神疾病风险之间的关系仍不清楚。
在本研究中，我们使用从费城神经发育队列（PNC）收集的数据（n = 1133名青少年）分析了杏仁核 - PFC回路成熟度的个体差异。使用深度学习建立杏仁核 - PFC静息态功能连接的神经发育模型，并对其进行训练以预测正常发育青少年（未暴露于暴力且无精神疾病诊断）的实际年龄。使用脑年龄差距估计（相对回路成熟度的指标），研究非典型神经发育模式。
暴力暴露与基底外侧杏仁核（BLA） - PFC回路成熟延迟有关，这是由BLA - 内侧眶额皮质功能连接增加所驱动的。相比之下，精神症状增加与BLA - PFC功能连接的提前成熟有关，这是由BLA - 背外侧PFC功能连接减少所驱动的。
暴露于暴力后额杏仁核成熟延迟表明威胁评估过程存在非典型但适应性的发展，这可能反映了年幼儿童更大的威胁泛化特征。随着症状增加回路成熟提前表明，在情绪回路适应逆境后，疾病背后存在不同的神经发育机制，而先前存在的早期成熟易感性会加剧这种情况。区分逆境和精神病理学对神经发育的影响对于帮助青少年从暴力中恢复并防止疾病持续到成年期至关重要。
