Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitudinal study.
Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitudinal study.
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DOI：
10.1001/jamapsychiatry.2014.1332
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发表时间：
2014-10
期刊：
影响因子：
25.8
通讯作者：
Jones PB
中科院分区：
文献类型：
--
作者：
Khandaker GM;Pearson RM;Zammit S;Lewis G;Jones PB
纵向研究已将全身性炎症标志物白细胞介素6（IL - 6）和C反应蛋白（CRP）与患心脏病和糖尿病的风险联系起来，而心脏病和糖尿病是抑郁症和精神病常见的合并症。近期对横断面研究的荟萃分析报告称，抑郁症、首发精神病和急性精神病复发患者的这些炎症标志物血清水平升高；然而，这种关联的方向尚不明确。
为了验证儿童时期血清IL - 6和CRP水平较高会增加日后患抑郁症和精神病风险这一假设。
雅芳父母与儿童纵向研究（ALSPAC）是一项在英格兰雅芳郡进行的前瞻性普通人群出生队列研究。我们研究了该队列中约4500人的一个子样本，这些人有儿童时期IL - 6和CRP水平的数据以及后来的精神疾病评估资料。
在参与者9岁时采集的非空腹血液样本中测量了IL - 6和CRP的水平。
参与者在18岁时接受评估。抑郁症通过《临床访谈量表修订版》（CIS - R）和《情绪和感受问卷》（MFQ）进行测量，从而可以进行内部重复验证；精神病性体验（PEs）和精神病性障碍通过半结构化访谈进行测量。
在对性别、年龄、体重指数、种族、社会阶层、既往心理和行为问题以及母亲产后抑郁症进行调整后，9岁时IL - 6值处于最高三分位的参与者与处于最低三分位的参与者相比，在18岁时更有可能患抑郁症（CIS - R）（调整后的优势比[OR]，1.55；95%置信区间，1.13 - 2.14）。使用MFQ的结果相似。18岁时PEs和精神病性障碍的风险也随着基线时IL - 6水平升高而增加（调整后的OR，1.81；95%置信区间，1.01 - 3.28；调整后的OR，2.40；95%置信区间，0.88 - 6.22）。儿童时期较高的IL - 6水平与随后患抑郁症和PEs的风险呈剂量依赖性相关。
儿童时期全身性炎症标志物IL - 6水平较高与青年期患抑郁症和精神病的风险增加有关。炎症通路可能为这些疾病提供重要的新的干预和预防靶点。炎症或许可以解释心脏病、糖尿病、抑郁症和精神分裂症之间的高合并症现象。
Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear. To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis. The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments. Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years. Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule–Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview. After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner. Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.