Department of Psychiatry, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, United Kingdom.
Brain Behav Immun. 2022 Mar;101:146-152. doi: 10.1016/j.bbi.2021.12.022. Epub 2021 Dec 29.
The study of neural-endocrine-immune system interactions has led to substantial advances in our understanding of neuropsychiatric disorders. Growing evidence reveals the pivotal roles of inflammatory cytokines signalling the brain to produce neurochemical, neuroendocrine, and neuroimmune changes which affect mood and behaviour. Ageing is accompanied by the development of low-grade systemic inflammation which may promote changes in the neural systems predisposing to geriatric depression via the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to investigate the longitudinal associations between baseline values and conditional changes (independent of baseline) in immune-endocrine biomarkers and mental health status in a population-based cohort of older adults.
Data from 347 subjects (200 men, 147 women) who participated in the Hertfordshire Ageing Study at baseline (1994/5, mean age 67.3 years) and at 9-year follow-up were analysed. Serum samples for analysis of inflammatory and endocrinological measures were collected at baseline and follow-up. At follow-up, depression (Hospital Anxiety and Depression Scale) and mental health (Short Form-36 questionnaire) were assessed. Baseline values and changes in biomarkers in relation to risk of high depression scores (top sex-specific third) and low mental health scores (bottom sex-specific third) were examined using logistic regression.
Lower baseline cortisol was related to greater risk of high depression scores; higher baseline cortisol: dehydroepiandrosterone sulphate ratio (men only) and higher baseline C-reactive protein (CRP) (women only) were related to greater risk of poor mental health scores. In addition, greater decline in cortisol was related to increased risk of high depression scores among men. These relationships were robust (p < 0.05) after controlling for sex, age, BMI, smoking, alcohol consumption and number of systems medicated.
This study provides further evidence of the role of the HPA axis and inflammation in older adults with poor mental health. In addition, the findings highlight sex differences where increased inflammation in women and declines in cortisol in men were linked to poorer mental health. Further research is warranted to confirm these findings. This could lead to the search for potential biomarkers to stratify medications as well as developing novel intervention targets to improve mental health at older age.
神经内分泌免疫系统相互作用的研究使我们对神经精神疾病的认识有了很大的进展。越来越多的证据表明，炎症细胞因子向大脑发出信号，导致神经化学、神经内分泌和神经免疫发生变化，从而影响情绪和行为，这一作用至关重要。随着年龄的增长，会出现低度的全身炎症，这可能会通过下丘脑-垂体-肾上腺（HPA）轴促进神经系统发生变化，从而导致老年抑郁症。本研究旨在调查人群为基础的老年队列中，基线值以及免疫内分泌生物标志物的条件变化（与基线值无关）与心理健康状况之间的纵向关联。
对参加 1994/5 年基线（平均年龄 67.3 岁）和 9 年随访的 347 名受试者（200 名男性，147 名女性）的数据进行了分析。在基线和随访时采集血清样本以分析炎症和内分泌指标。在随访时，评估了抑郁（医院焦虑抑郁量表）和心理健康（简短形式 36 问卷）。使用逻辑回归分析了基线值和生物标志物的变化与高抑郁评分（男性和女性中最高三分之一）和低心理健康评分（男性和女性中最低三分之一）风险之间的关系。
较低的基线皮质醇与较高的高抑郁评分风险相关；较高的基线皮质醇：脱氢表雄酮硫酸盐比值（仅男性）和较高的基线 C 反应蛋白（仅女性）与较低的心理健康评分风险相关。此外，皮质醇的较大下降与男性中高抑郁评分风险的增加有关。这些关系在控制了性别、年龄、BMI、吸烟、饮酒和系统用药数量后仍然具有稳健性（p<0.05）。
本研究进一步证明了 HPA 轴和炎症在心理健康状况较差的老年人群中的作用。此外，研究结果还突出了性别差异，女性的炎症增加和男性的皮质醇下降与较差的心理健康相关。需要进一步的研究来证实这些发现。这可能会导致寻找潜在的生物标志物来分层药物治疗以及开发改善老年人群心理健康的新干预靶点。
