Mehrhof Sara Z, Fleming Hugo, Nord Camilla L
MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Sci Adv. 2025 Sep 26;11(39):eady4356. doi: 10.1126/sciadv.ady4356. Epub 2025 Sep 24.
Mental health conditions like depression are associated with an elevated risk of cardiometabolic disorders, yet the mechanisms underlying this comorbidity remain poorly understood. Is metabolic dysfunction a cause of depression, a downstream consequence, or do both stem from shared underlying processes? We argue that neurocognitive mechanisms, particularly those involved in reward and effort processing, interact with metabolic physiology to shape each of these causal pathways. Metabolic signals do not act on the brain in isolation; they are embedded within a broader interoceptive system through which the brain detects and interprets bodily states. This system supports allostasis, the brain's predictive regulation of internal physiological demands. We propose a framework of interoceptive energy allostasis in which disruptions to these predictive processes contribute to the bidirectional relationship between depression and metabolic dysfunction. By integrating perspectives from metabolic and computational psychiatry, this framework offers a theoretical lens to explain the multidirectional comorbidity between mental and metabolic ill-health.
抑郁症等心理健康状况与心血管代谢紊乱风险升高有关，但这种共病的潜在机制仍知之甚少。代谢功能障碍是抑郁症的病因、下游后果，还是两者都源于共同的潜在过程？我们认为，神经认知机制，尤其是那些参与奖赏和努力加工的机制，与代谢生理学相互作用，从而塑造了这些因果途径中的每一条。代谢信号并非孤立地作用于大脑；它们嵌入在一个更广泛的内感受系统中，大脑通过该系统检测和解释身体状态。这个系统支持内环境稳定，即大脑对内部生理需求的预测性调节。我们提出了一个内感受能量内环境稳定的框架，其中这些预测过程的破坏导致了抑郁症与代谢功能障碍之间的双向关系。通过整合代谢精神病学和计算精神病学的观点，这个框架提供了一个理论视角来解释精神和代谢性健康不良之间的多向共病现象。
