PDF(Pubmed)
Abstract：
Depression is a serious public health problem, and adolescence is an \'age of risk\' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico-amygdala circuit, lowers sensitivity to rewards in the cortico-striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self-medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress-related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a \'next generation\' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents.
摘要：
抑郁症是一个严重的公共卫生问题，青春期是严重抑郁症发病的“危险年龄”。最近,我们和其他人提出了神经免疫网络模型，强调大脑和免疫系统在身心健康方面的双向通信，包括抑郁症。这些模型利用研究表明，协调外周炎症的细胞参与者（特别是单核细胞）和信号分子（特别是细胞因子）可以直接调节大脑的结构和功能。在大脑中,炎症活动提高了对皮质-杏仁核回路威胁的敏感性，降低对皮质纹状体回路奖励的敏感性，改变前额叶皮层的执行控制和情绪调节。当失调时，特别是在慢性压力的情况下，炎症会产生烦躁不安的感觉，苦恼,和快感缺乏症。这是为了发起不健康的，自我用药行为(例如物质使用，不良饮食)来管理烦躁不安，这进一步加剧了炎症。随着时间的推移,这些大脑回路的失调和炎症反应可能会相互混合形成一个正反馈回路，其中一个器官系统的失调会加剧另一个器官系统。我们和其他人认为，这种神经免疫失调是抑郁症的动态联合脆弱性，特别是在青春期。本文有三个目标。首先,我们扩展了精神和身体健康的神经免疫网络模型，以建立青春期抑郁症发作风险的发展框架。第二,我们研究了神经免疫网络的观点如何帮助解释抑郁症和其他精神疾病在整个发展过程中的高合并症率，抑郁症和压力相关的医学疾病之间的多重性。最后,我们考虑如何识别神经免疫途径抑郁症可以促进“下一代”的行为和生物学干预，目标神经免疫信号进行治疗，理想情况下是防止，青少年抑郁症。
