Epidemiological evidence indicates the presence of dysregulated homeostatic biological pathways in depressed patients, such as increased inflammation and disrupted energy-regulating neuroendocrine signaling (e.g., leptin, insulin). Alterations in these biological pathways may explain the considerable comorbidity between depression and cardiometabolic conditions (e.g., obesity, metabolic syndrome, diabetes) and represent a promising target for intervention. This review describes how immunometabolic dysregulations vary as a function of depression heterogeneity by illustrating that such biological dysregulations map more consistently to atypical behavioral symptoms reflecting altered energy intake/expenditure balance (hyperphagia, weight gain, hypersomnia, fatigue, and leaden paralysis) and may moderate the antidepressant effects of standard or novel (e.g., anti-inflammatory) therapeutic approaches. These lines of evidence are integrated in a conceptual model of immunometabolic depression emerging from the clustering of immunometabolic biological dysregulations and specific behavioral symptoms. The review finally elicits questions to be answered by future research and describes how the immunometabolic depression dimension could be used to dissect the heterogeneity of depression and potentially to match subgroups of patients to specific treatments with higher likelihood of clinical success.

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抑郁症的异质性及其生物学基础：免疫代谢性抑郁症

流行病学证据表明抑郁症患者存在失调的稳态生物途径，例如炎症增加和能量调节神经内分泌信号（例如瘦素、胰岛素）中断。这些生物学途径的改变可以解释抑郁症和心脏代谢疾病（例如肥胖、代谢综合征、糖尿病）之间存在相当多的共病，并代表了一个有希望的干预目标。这篇综述描述了免疫代谢失调如何作为抑郁症异质性的函数而变化，通过说明这种生物失调更一致地映射到反映能量摄入/支出平衡改变的非典型行为症状（食欲过盛、体重增加、嗜睡、疲劳、和铅麻痹）并可能减轻标准或新型（例如抗炎）治疗方法的抗抑郁作用。这些证据被整合到免疫代谢性抑郁症的概念模型中，该模型源于免疫代谢生物学失调和特定行为症状的聚集。该综述最终提出了未来研究需要回答的问题，并描述了如何使用免疫代谢抑郁维度来剖析抑郁症的异质性，并有可能将患者亚组与具有更高临床成功可能性的特定治疗相匹配。这些证据被整合到免疫代谢性抑郁症的概念模型中，该模型源于免疫代谢生物学失调和特定行为症状的聚集。该综述最终提出了未来研究需要回答的问题，并描述了如何使用免疫代谢抑郁维度来剖析抑郁症的异质性，并有可能将患者亚组与具有更高临床成功可能性的特定治疗相匹配。这些证据被整合到免疫代谢性抑郁症的概念模型中，该模型源于免疫代谢生物学失调和特定行为症状的聚集。该综述最终提出了未来研究需要回答的问题，并描述了免疫代谢抑郁维度如何用于剖析抑郁症的异质性，并有可能将患者亚组与具有更高临床成功可能性的特定治疗相匹配。