Son Jake J, Suk Ji-Woo, Garvey William F, Edwards Ryan T, Leibenluft Ellen, Blair R J R, Hwang Soonjo
College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Korean Institute of Alternative Medicine, Daejon 34054, Republic of Korea.
Life (Basel). 2025 Aug 7;15(8):1253. doi: 10.3390/life15081253.
Irritability and reactive aggression are transdiagnostic features that are predictive of adverse long-term outcomes. This investigation examined whether intranasal oxytocin administration impacts the interaction between irritability and reactive aggression, and whether these effects can be detected at a neural level via a facial expression processing task during functional MRI (fMRI).
In this study, 40 children and adolescents with severe irritability and psychiatric diagnoses of disruptive mood and behavioral disorders were assigned to either intranasal oxytocin or placebo administration over a 3-week period in a randomized, double-blind trial (ClinicalTrials, NCT02824627). Clinical measures and fMRI during a facial expression processing task were collected pre- and post-intervention. Brain regions sensitive to oxytocin administration were determined using whole-brain statistical analyses, with post hoc analyses to determine whether changes in the neural activity mediated the relationship between changes in irritability and reactive aggression across the intervention period.
Youth who received intranasal oxytocin administration exhibited significant decreases in irritability and reactive aggression compared to their counterparts in the placebo group. Further, oxytocin administration was associated with significant increases in neural activity in the right superior prefrontal cortex, which fully mediated the relationship between improvements in irritability and improvements in reactive aggression.
Intranasal oxytocin significantly reduced irritability and reactive aggression in youth, as well as neural activity in the prefrontal cortex, such that increases in the cortical activity fully mediated the relationship between changes in irritability and reactive aggression. Taken together, these findings may reflect oxytocin-related enhancements in emotional regulation in youth with severe irritability, a potential therapeutic mechanism for mitigating reactive aggression.
易怒和反应性攻击是跨诊断特征，可预测不良的长期后果。本研究调查了鼻内给予催产素是否会影响易怒与反应性攻击之间的相互作用，以及这些影响是否能通过功能磁共振成像（fMRI）期间的面部表情处理任务在神经层面被检测到。
在本研究中，40名患有严重易怒且有破坏性行为和情绪障碍精神诊断的儿童和青少年，在一项为期3周的随机双盲试验（ClinicalTrials，NCT02824627）中被分配接受鼻内催产素或安慰剂给药。在干预前后收集面部表情处理任务期间的临床测量数据和fMRI数据。使用全脑统计分析确定对催产素给药敏感的脑区，并进行事后分析以确定神经活动的变化是否介导了整个干预期内易怒和反应性攻击变化之间的关系。
与安慰剂组的同龄人相比，接受鼻内催产素给药的青少年在易怒和反应性攻击方面表现出显著下降。此外，给予催产素与右侧额上前皮质神经活动的显著增加相关，这完全介导了易怒改善与反应性攻击改善之间的关系。
鼻内给予催产素显著降低了青少年的易怒和反应性攻击，以及前额叶皮质的神经活动，使得皮质活动的增加完全介导了易怒和反应性攻击变化之间的关系。综上所述，这些发现可能反映了催产素相关的对严重易怒青少年情绪调节的增强作用，这是减轻反应性攻击的一种潜在治疗机制。
