Early-life inflammatory markers and subsequent psychotic and depressive episodes between 10 to 28 years of age.
Early-life inflammatory markers and subsequent psychotic and depressive episodes between 10 to 28 years of age.
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DOI：
10.1016/j.bbih.2022.100528
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发表时间：
2022-12
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炎症与抑郁症和精神病有关，包括儿童炎症标志物与随后出现症状的风险之间的关联。然而，尚不清楚早期炎症标记物是否与儿童到成年的抑郁和精神病症状的数量有关。使用前瞻性雅芳儿童和父母纵向研究出生队列（N = 6401），我们研究了早期炎症的纵向相关性[暴露：9岁时的白细胞介素-6（IL-6）、C反应蛋白（CRP）水平;出生时和7岁时的IL-6和CRP DNA甲基化（DNAm）评分;和IL-6和CRP多基因风险评分（PRS）]与10-28岁之间的抑郁发作和精神病经历（PE）的数量。精神病学的结果进行了评估，分别使用简短的情绪和感觉问卷和精神病样症状量表。使用负二项模型检验暴露-结局相关性，该模型根据代谢和社会人口统计学因素进行了调整。在基础模型中，9岁时的血清IL-6水平与10 - 28岁之间的抑郁发作总数相关（n = 4835; β = 0.066; 95%CI：0.020-0.113; pFDR = 0.041），当调整代谢和社会人口因素时，该模型较弱。炎症标志物（血清IL-6和CRP DNA m评分）与PE总数之间存在弱相关性。其他炎症标志物与抑郁或PE无关。早期炎症标志物与抑郁发作和随后从儿童到成年的PE的负担相关。这些发现支持了早期炎症在抑郁症和精神病病因学中的潜在作用，并强调炎症是治疗和预防的潜在目标。早期生活炎症与以后生活中疾病负担的纵向证据。我们探索了炎症的血清、遗传和表观遗传生物标志物。在16个时间点（10-28岁）观察结果。血清IL-6（9岁）与抑郁发作的总次数密切相关。CRP DNAm评分与精神病经历总数弱相关。
Inflammation is implicated in depression and psychosis, including association of childhood inflammatory markers on the subsequent risk of developing symptoms. However, it is unknown whether early-life inflammatory markers are associated with the number of depressive and psychotic symptoms from childhood to adulthood. Using the prospective Avon Longitudinal Study of Children and Parents birth cohort (N = up-to 6401), we have examined longitudinal associations of early-life inflammation [exposures: interleukin-6 (IL-6), C-reactive protein (CRP) levels at age 9y; IL-6 and CRP DNA-methylation (DNAm) scores at birth and age 7y; and IL-6 and CRP polygenic risk scores (PRSs)] with the number of depressive episodes and psychotic experiences (PEs) between ages 10–28 years. Psychiatric outcomes were assessed using the Short Mood and Feelings Questionnaire and Psychotic Like Symptoms Questionnaires, respectively. Exposure-outcome associations were tested using negative binomial models, which were adjusted for metabolic and sociodemographic factors. Serum IL-6 levels at age 9y were associated with the total number of depressive episodes between 10 and 28y in the base model (n = 4835; β = 0.066; 95%CI:0.020–0.113; pFDR = 0.041) which was weaker when adjusting for metabolic and sociodemographic factors. Weak associations were observed between inflammatory markers (serum IL-6 and CRP DNAm scores) and total number of PEs. Other inflammatory markers were not associated with depression or PEs. Early-life inflammatory markers are associated with the burden of depressive episodes and of PEs subsequently from childhood to adulthood. These findings support a potential role of early-life inflammation in the aetiology of depression and psychosis and highlight inflammation as a potential target for treatment and prevention. Longitudinal evidence of early-life inflammation with illness burden later in life. We explored serum, genetic and epigenetic biomarkers of inflammation. Outcomes were observed at 16 time-points (10–28 years of age). Serum IL-6 (age 9) strongly associated with total number of depressive episodes. CRP DNAm scores weakly associated with total number of psychotic experiences.