Gold Coast Hospital and Health Service, Southport, Australia.
Faculty of Health Sciences and Medicine, Bond University, Robina, Australia.
Cogn Affect Behav Neurosci. 2018 Dec;18(6):1121-1144. doi: 10.3758/s13415-018-0626-0.
Major depressive disorder (MDD) and obesity are dominant and inter-related health burdens. Obesity is a risk factor for MDD, and there is evidence MDD increases risk of obesity. However, description of a bidirectional relationship between obesity and MDD is misleading, as closer examination reveals distinct unidirectional relationships in MDD subtypes. MDD is frequently associated with weight loss, although obesity promotes MDD. In contrast, MDD with atypical features (MDD-AF) is characterised by subsequent weight gain and obesity. The bases of these distinct associations remain to be detailed, with conflicting findings clouding interpretation. These associations can be viewed within a systems biology framework-the psycho-immune neuroendocrine (PINE) network shared between MDD and metabolic disorders. Shared PINE subsystem perturbations may underlie increased MDD in overweight and obese people (obesity-associated depression), while obesity in MDD-AF (depression-associated obesity) involves more complex interactions between behavioural and biomolecular changes. In the former, the chronic PINE dysfunction triggering MDD is augmented by obesity-dependent dysregulation in shared networks, including inflammatory, leptin-ghrelin, neuroendocrine, and gut microbiome systems, influenced by chronic image-associated psychological stress (particularly in younger or female patients). In MDD-AF, behavioural dysregulation, including hypersensitivity to interpersonal rejection, fundamentally underpins energy imbalance (involving hyperphagia, lethargy, hypersomnia), with evolving obesity exaggerating these drivers via positive feedback (and potentially augmenting PINE disruption). In both settings, sex and age are important determinants of outcome, associated with differences in emotional versus cognitive dysregulation. A systems biology approach is recommended for further research into the pathophysiological networks underlying MDD and linking depression and obesity.
重度抑郁症（MDD）和肥胖是主要且相互关联的健康负担。肥胖是 MDD 的一个风险因素，有证据表明 MDD 会增加肥胖的风险。然而，将肥胖和 MDD 之间的双向关系描述为误导性的，因为更仔细的检查揭示了 MDD 亚型中存在明显的单向关系。MDD 通常与体重减轻有关，尽管肥胖会促进 MDD。相比之下，具有非典型特征的 MDD（MDD-AF）的特征是随后的体重增加和肥胖。这些不同关联的基础仍有待详细描述，相互矛盾的发现使解释变得复杂。这些关联可以在系统生物学框架内进行观察——MDD 和代谢紊乱之间共享的心理-免疫神经内分泌（PINE）网络。共享 PINE 子系统的干扰可能是超重和肥胖人群中 MDD 增加的基础（与肥胖相关的抑郁症），而 MDD-AF 中的肥胖（与抑郁症相关的肥胖）涉及行为和生物分子变化之间更复杂的相互作用。在前者中，慢性 PINE 功能障碍触发 MDD 的机制是由共享网络中肥胖依赖性失调引起的，包括炎症、瘦素-饥饿素、神经内分泌和肠道微生物组系统，这些系统受慢性与形象相关的心理压力影响（特别是在年轻或女性患者中）。在 MDD-AF 中，行为失调，包括对人际拒绝的过度敏感，从根本上导致能量失衡（涉及暴食、嗜睡、嗜睡），随着肥胖的发展，这些驱动因素通过正反馈加剧（并可能加剧 PINE 破坏）。在这两种情况下，性别和年龄都是结局的重要决定因素，与情绪与认知失调的差异有关。建议采用系统生物学方法进一步研究 MDD 背后的病理生理网络，并将抑郁和肥胖联系起来。
