Zhang Kristina, Ibrahim George M, Venetucci Gouveia Flavia
Institute of Medical Science, University of Toronto, Toronto, ON M5S 3H2, Canada.
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Int J Mol Sci. 2025 Feb 24;26(5):1938. doi: 10.3390/ijms26051938.
Nonsuicidal self-injurious behaviour (SIB) is a debilitating manifestation of physical aggression commonly observed across neurodevelopmental, psychiatric, and genetic disorders. This behaviour arises from a multifactorial aetiology involving genetic predispositions, epigenetic modifications, neurotransmitter dysregulation, and environmental stressors. Dysregulation in dopaminergic, serotonergic, glutamatergic, and GABAergic systems has been implicated in the pathophysiology of SIB, alongside structural and functional abnormalities within fronto-limbic-striatal circuits. These disruptions impair key processes, such as emotional regulation, reward processing, and behavioural inhibition, contributing to the emergence and reinforcement of SIB. Advances in preclinical research using genetic, lesion-based, pharmacological, and environmental animal models have been instrumental in elucidating the molecular and neurocircuitry underpinnings of SIB. Emerging neuromodulation therapies targeting critical nodes within the fronto-limbic-striatal network, particularly deep brain stimulation, have shown promise in treating severe, refractory SIB and improving quality of life. This review integrates current evidence from clinical studies, molecular research, and preclinical models to provide a comprehensive overview of the pathophysiology of SIB and therapeutic approaches. By focusing on the molecular mechanisms and neural circuits underlying SIB, we highlight the translational potential of emerging pharmacological and neuromodulatory therapies. A deeper understanding of these pathways will pave the way for precision-based interventions, bridging the gap between molecular research and clinical applications in SIB and related conditions.
非自杀性自伤行为（SIB）是一种常见于神经发育、精神和遗传疾病中的身体攻击性行为的衰弱表现。这种行为源于多因素病因，涉及遗传易感性、表观遗传修饰、神经递质失调和环境应激源。多巴胺能、血清素能、谷氨酸能和γ-氨基丁酸能系统的失调与SIB的病理生理学有关，同时额叶-边缘-纹状体回路内存在结构和功能异常。这些破坏会损害关键过程，如情绪调节、奖赏处理和行为抑制，从而导致SIB的出现和强化。利用遗传、基于损伤、药理学和环境动物模型的临床前研究进展，有助于阐明SIB的分子和神经回路基础。针对额叶-边缘-纹状体网络内关键节点的新兴神经调节疗法，特别是深部脑刺激，在治疗严重难治性SIB和改善生活质量方面已显示出前景。本综述整合了临床研究、分子研究和临床前模型的现有证据，以全面概述SIB的病理生理学和治疗方法。通过关注SIB背后的分子机制和神经回路，我们强调了新兴药理学和神经调节疗法的转化潜力。对这些途径的更深入理解将为基于精准的干预措施铺平道路，弥合SIB及相关病症的分子研究与临床应用之间的差距。
