{"_":" 探讨嘌呤能P2X7作为自杀风险潜在生物标志物：一个假设。","i":["体内"]}

摘要(中文译文)

自杀每年在全球夺去超过72万人的生命，而每一次自杀背后都有更多人曾尝试自杀，自杀意念则更为普遍。为改善对自杀行为高风险个体的识别，需要研究风险因素与神经生物学机制之间的关系。本文提出一个整合性神经生物学假说，将童年逆境这一已知的自杀未遂风险因素与有童年逆境背景个体的心理痛苦体验联系起来。意念-行动理论提出，除绝望感外，心理痛苦也与自杀意念相关，而习得的自杀尝试能力则使自杀想法进展为自杀行为。本文提出一个心理悖论：暴露于童年逆境的个体一方面对心理痛苦更为脆弱（心理痛苦是自杀意念的驱动因素），另一方面身体疼痛耐受性增高且对死亡的无畏程度增加，从而促进自杀能力。疼痛感知可能受神经生物学调控。嘌呤能通路及嘌呤能受体（如P2X7受体过度激活）的失调可能通过至少三种平行机制促成自杀性：通过含NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎症小体激活介导的神经炎症、前扣带皮层谷氨酸能失调，以及通过脑源性神经营养因子（BDNF）介导的氯化钾协同转运蛋白2（KCC2）下调破坏抑制性疼痛与恐惧环路。嘌呤能失调与自杀行为风险增加相关，这已在双相障碍、抑郁障碍和精神分裂症中得到证实。来自遗传学研究、外周炎症生物标志物和死后脑组织的汇聚证据表明，自杀性中的P2X7失调具有细胞类型和脑区特异性，最直接的证据来自独立于精神科诊断的自杀死亡个体的死后发现。这些神经生物学改变可能在急性危机期间降低自杀行为的门槛。使用[¹¹C]SMW139或[¹¹C]JNJ717的PET可通过与P2X7受体的高亲和力结合使嘌呤能通路可视化。我们假设受体过度激活与急性自杀性相关，因而也与心理痛苦相关。该方法为生物标志物开发以及针对自杀性神经免疫基质的靶向治疗干预提供了潜力。

Abstract

Suicide claims over 720,000 lives annually worldwide and for every suicide there are many more people who attempt suicide and with suicidal ideation being even more prevalent. To improve the identification of individuals at high risk for suicidal behavior, there is a need to study risk factors in relation to neurobiological mechanisms. This paper proposes an integrative neurobiological hypothesis linking childhood adversity as a known risk factor for suicide attempts and the experience of mental pain in individuals with childhood adversity in their background. The ideation-to-action theory proposes that psychological pain, in addition to hopelessness, is associated with suicide ideation, whereas the acquired capability to attempt suicide enables the progression from suicidal thought to suicidal behavior. A psychological paradox is suggested wherein childhood adversity exposed individuals are more vulnerable for psychological pain, a driver for suicidal ideation, alongside increased physical pain tolerance and fearlessness about death fostering suicide capability. Pain perception may be neurobiologically regulated. Dysregulation of the purinergic pathway and purinergic receptors, such as overactivation of the P2X7 receptor, may contribute to suicidality through at least three parallel mechanisms: neuroinflammation via NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation, glutamatergic dysregulation in the anterior cingulate cortex, and disruption of inhibitory pain and fear circuits via brain-derived neurotrophic factor (BDNF) -mediated potassium chloride cotransporter 2 (KCC2) downregulation. Purinergic dysregulation is associated with increased risk for suicidal behavior, which has been demonstrated in bipolar and depressive disorders and schizophrenia. Converging evidence from genetic studies, peripheral inflammatory biomarkers, and postmortem brain tissue indicates that P2X7 dysregulation in suicidality is cell-type and region-specific, with the most direct evidence coming from postmortem findings in individuals who died by suicide independent of psychiatric diagnosis. These neurobiological changes may lower barriers to suicidal behavior during acute crises. PET with [C]SMW139 or [C]JNJ717 can visualize the purinergic pathway through high-affinity binding to the P2X7 receptor. We hypothesize that receptor overactivation is associated with acute suicidality, hence psychological pain. This approach offers potential for biomarker development and targeted therapeutic interventions addressing the neuro-immune substrate of suicidality.

如何引用

Frontiers in psychiatry 的其他文献

• ADOS-2在真实世界临床转诊人群中各模块的诊断准确性：一项更新的系统综述和HSROC荟萃分析
• 长期使用含替雷他明的电子烟后持续性神经精神功能障碍：病例报告
• 疲劳大鼠模型的认知障碍和前额叶TGF-β1升高
• 中国男性酒精依赖患者在语言流畅性任务中的额颞皮质活动：一项功能性近红外光谱研究
• 双相I型与双相II型障碍的工作记忆网络功能障碍：任务功能磁共振成像证据的系统综述
• 全身炎症综合指数在儿童情绪忽视和重度抑郁症抑郁严重程度之间的中介作用：一项横断面研究
• 智能手机成瘾、负面情绪和心理韧性在医学生社会支持与睡眠质量关系中的中介作用
• 剖宫产后诊断为双相情感障碍的患者产后谵妄躁狂：病例报告
• 全身免疫炎症指数与卒中后抑郁的关系：荟萃分析
• 用于早期阿尔茨海默病检测的多模式非侵入性方法：神经电生理学和神经影像学技术综述