Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels – both of which are closely linked to diet – all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.

饮食等环境因素与抑郁症和/或晚年复发风险有关。这可能部分是由食物代谢组驱动的，食物代谢组通过循环系统与大脑交流，并与海马神经发生 (HN) 相互作用，海马神经发生是一种与抑郁症病因有关的大脑可塑性形式。尽管 HN、饮食和抑郁症之间存在关联，但进一步证实这一假设的人类数据在很大程度上是缺失的。在这里，我们使用 HN 的体外模型来测试来自 373 名参与者的纵向老化队列的血清样本的影响，有或没有抑郁症状。将 1% 的参与者血清应用于人类胎儿海马祖细胞，HN 标记物的变化与 12 年期间抑郁症状的发生有关。关键营养，随后测试了代谢组学和脂质组学生物标志物（从参与者血浆和血清中提取）调节 HN 的能力。在我们的测定中，我们发现细胞死亡减少和神经元分化增加与晚年抑郁症状相关。此外，我们发现在 12 年期间经历反复抑郁症状的参与者的血清处理的细胞中神经元细胞形态存在损伤。有趣的是，我们发现增加的神经元分化受代谢物丁酰肉碱血清水平升高和甘油磷脂水平降低，PC35:1(16:0/19:1) 水平的调节——这两者都与饮食密切相关——所有这些都是在抑郁症状学。