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.

中文翻译：

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年度研究回顾：抑郁症的神经免疫网络模型：发展视角

抑郁症是一个严重的公共卫生问题，青春期是重度抑郁症发病的“高危年龄”。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之间在心理和身体健康（包括抑郁症）中的双向通信。这些模型利用的研究表明，协调外周炎症的细胞因子（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，炎症活动会提高皮质-杏仁核回路中对威胁的敏感性，降低皮质-纹状体回路中对奖励的敏感性，并改变前额皮质中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、痛苦和快感缺乏的感觉。这被认为是为了引发不健康的自我治疗行为（例如物质使用、不良饮食）来控制烦躁不安，从而进一步加剧炎症。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复合，形成正反馈循环，从而一个器官系统的失调会加剧另一个器官系统的失调。我们和其他人认为，这种神经免疫失调是抑郁症的动态关节脆弱性，特别是在青春期。我们对本文有三个目标。首先，我们扩展了心理和身体健康的神经免疫网络模型，以生成青春期抑郁症发作风险的发展框架。其次，我们研究神经免疫网络视角如何帮助解释抑郁症和其他精神疾病在整个发育过程中的高共病率，以及抑郁症和压力相关疾病之间的多重发病率。最后，我们考虑如何确定抑郁症的神经免疫途径可以促进“下一代”行为和生物干预措施，这些干预措施以神经免疫信号传导为目标，以治疗并理想地预防青少年的抑郁症。