Childhood immuno-metabolic markers and risk of depression and psychosis in adulthood: A prospective birth cohort study
Childhood immuno-metabolic markers and risk of depression and psychosis in adulthood: A prospective birth cohort study
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DOI：
10.1101/2021.11.19.21266562
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发表时间：
2021-11
影响因子：
3.7
通讯作者：
N. Donnelly;B. Perry;H. Jones;G. Khandaker
中科院分区：
文献类型：
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作者：
N. Donnelly;B. Perry;H. Jones;G. Khandaker
代谢和炎症性疾病通常与抑郁症和精神病同时发生，新出现的证据表明其病因与免疫代谢功能障碍有关。先前的研究报告了患有抑郁症和精神病的成年人的代谢功能障碍和炎症。然而，纵向研究测试协会的方向，以及不同层面的早期生活免疫代谢功能障碍对成人精神病理学的影响，是有限的。使用来自3875名出生队列参与者的数据，我们研究了9岁时三种代谢激素（瘦素，脂联素，胰岛素）与24岁时抑郁症和精神病谱结局风险的纵向关联。此外，使用九种免疫代谢生物标志物，我们构建了一个探索性双因素模型，显示了一个一般的免疫代谢因素和三个特定的因素（肥胖，炎症和胰岛素抵抗），这也被用作暴露。儿童期瘦素与成人期抑郁发作（校正比值比（aOR）=1.28; 95%CI，1.00-1.64）和阴性症状（aOR=1.12; 95%CI，1.05-1.20）相关。一般免疫代谢因素与抑郁症状（aOR=1.05; 95%CI，1.01-1.08）和精神病经历（aOR=1.20; 95%CI，1.01-1.42）相关。肥胖因素与阴性症状相关（aOR=1.07; 95%CI 1.02-1.12）。尽管95%的可信区间与男性重叠，但所有相关性在女性中往往更强。在女性中，炎症因子与抑郁发作（aOR=1.23; 95%CI，1.01-1.47）和非典型抑郁症状（aOR=1.10; 95%CI，1.02-1.19）相关。虽然儿童期的一般免疫代谢功能障碍可能会导致成年后精神病和抑郁症状的风险，但儿童肥胖和炎症与情感（抑郁，非典型和阴性）症状有关。
Metabolic and inflammatory disorders commonly co-occur with depression and psychosis, with emerging evidence implicating immuno-metabolic dysfunction in their aetiology. Previous studies have reported metabolic dysfunction and inflammation in adults with depression and psychosis. However, longitudinal studies testing the direction of association, and the effects of different dimensions of early-life immuno-metabolic dysfunction on adult psychopathology, are limited. Using data from 3875 birth cohort participants we examined longitudinal associations of three metabolic hormones (leptin, adiponectin, insulin) at age 9 with risks for depression- and psychosis-spectrum outcomes at age 24. In addition, using nine immuno-metabolic biomarkers, we constructed an exploratory bifactor model showing a general immuno-metabolic factor and three specific factors (adiposity, inflammation, and insulin resistance), which were also used as exposures. Childhood leptin was associated with adult depressive episode (adjusted odds ratio (aOR)=1.28; 95% CI, 1.00-1.64) and negative symptoms (aOR=1.12; 95% CI, 1.05-1.20). The general immuno-metabolic factor was associated with depressive symptoms (aOR=1.05; 95% CI, 1.01-1.08) and psychotic experiences (aOR=1.20; 95% CI, 1.01-1.42). The adiposity factor was associated with negative symptoms (aOR=1.07; 95% CI 1.02-1.12). All associations tended to be stronger in women, though 95% credible intervals overlapped with that for men. In women, the inflammatory factor was associated with depressive episode (aOR=1.23; 95% CI, 1.01-1.47) and atypical depressive symptoms (aOR=1.10; 95% CI, 1.02-1.19). While general immuno-metabolic dysfunction in childhood may contribute to risks for both psychotic and depressive symptoms in adulthood, childhood adiposity and inflammation are linked to affective (depressive, atypical, and negative) symptoms.