Jin Rachel R, Wong Nichol M L, Ma Junji, Fang Ji-Tseng, Lin Chih-Ming, Toh Cheng Hong, Wu Kuan-Yi, Hsu Jung Lung, Huang Chih-Mao, Lee Shwu Hua, Lee Tatia M C
Laboratory of Neuropsychology and Human Neuroscience, The University of Hong Kong, Hong Kong SAR, China.
InnoCentre of Clinical Neuropsychology, The University of Hong Kong, Hong Kong SAR, China.
Transl Psychiatry. 2025 Aug 29;15(1):328. doi: 10.1038/s41398-025-03547-5.
Depression is highly prevalent among older people globally. It is well known that childhood trauma and loneliness are significant risk factors for depression, and neural alterations in the default mode network and immunological dysregulation (e.g., neutrophil-to-lymphocyte ratio) are factors significantly associated with loneliness and depression. This study examined the inter-relationships and interactions of these factors for translational insight into the pathophysiological underpinnings of late-life depression. Among ninety-two healthy older adults, we measured the leukocyte distribution as reflected by neutrophil-to-lymphocyte ratio, childhood trauma history, current feelings of loneliness, and levels of depressive symptoms. All participants underwent structural MRI scanning to acquire T1-weighted images, which were used to measure the grey matter volume within the default mode network and its key regions. We observed that loneliness as a significant mediator explained the positive relationship between childhood emotional neglect and the severity of depression in late life. The modulating effect of grey matter volume in the default mode network depends on the level of neutrophil-to-lymphocyte ratio. In sum, our findings indicated that the more severe the lonely feeling those older people with childhood emotional neglect felt, the more the depressive symptoms were, which was especially obvious among those with relatively higher neutrophil-to-lymphocyte ratio and with lower grey matter volume in the default mode network. The current findings inspire future preventive and interventional studies targeting loneliness and inflammation to promote mental wellness in older adults.
抑郁症在全球老年人中极为普遍。众所周知，童年创伤和孤独是抑郁症的重要危险因素，默认模式网络中的神经改变和免疫失调（如中性粒细胞与淋巴细胞比率）是与孤独和抑郁症显著相关的因素。本研究探讨了这些因素之间的相互关系和相互作用，以便从转化医学角度深入了解晚年抑郁症的病理生理基础。在92名健康老年人中，我们测量了以中性粒细胞与淋巴细胞比率反映的白细胞分布、童年创伤史、当前的孤独感以及抑郁症状水平。所有参与者均接受了结构MRI扫描以获取T1加权图像，这些图像用于测量默认模式网络及其关键区域内的灰质体积。我们观察到，孤独作为一个显著的中介因素，解释了童年情感忽视与晚年抑郁症严重程度之间的正相关关系。默认模式网络中灰质体积的调节作用取决于中性粒细胞与淋巴细胞比率的水平。总之，我们的研究结果表明，那些童年有情感忽视的老年人孤独感越严重，抑郁症状就越多，这在那些中性粒细胞与淋巴细胞比率相对较高且默认模式网络灰质体积较低的老年人中尤为明显。目前的研究结果为未来针对孤独和炎症的预防及干预研究提供了启示，以促进老年人的心理健康。
