Cheslack-Postava Keely, Cremers Serge, Bao Yuanyuan, Shen Ling, Schaefer Catherine A, Brown Alan S
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, United States.
Pathology and Cell Biology, Columbia University Medical Center, New York, NY, United States.
Brain Behav Immun. 2017 Jul;63:108-114. doi: 10.1016/j.bbi.2016.07.160. Epub 2016 Jul 29.
Prenatal exposure to influenza has previously been associated with increased risk of bipolar disorder (BD), an association that may be mediated by maternal cytokines. The objective of this study was to determine the association between maternal levels of cytokines measured during each trimester of pregnancy and the risk of BD in offspring. We conducted a case-control study nested in the Child Health and Development Study, a birth cohort that enrolled pregnant women in 1959-1966. Potential cases with DSM-IV-TR bipolar I disorder, bipolar II disorder, BD not otherwise specified, and BD with psychotic features were ascertained through electronic medical records, a public agency database, and a mailing to the cohort. Diagnoses were confirmed by clinical interview. Nine cytokines (IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and GM-CSF) were measured simultaneously by Luminex assays in archived prenatal maternal serum samples from 85 cases and 170 matched controls. Data were analyzed using conditional logistic regression. In the overall study sample, there were no significant associations between prenatal maternal cytokine levels and BD after adjustment for confounders. The risk of BD without psychotic features was decreased among subjects with higher maternal levels of first trimester log-transformed IL-4 (OR (95% CI)=0.76 (0.58, 0.98); p=0.04) and third trimester log-transformed IL-6 (OR (95% CI)=0.64 (0.42, 0.98); p=0.04). In conclusion, higher levels of prenatal maternal cytokines were not associated with increased risk for BD. Further studies with larger samples are necessary to confirm the finding.
先前已有研究表明,产前暴露于流感病毒会增加患双相情感障碍(BD)的风险,这种关联可能由母体细胞因子介导。本研究的目的是确定孕期各阶段母体细胞因子水平与后代患BD风险之间的关联。我们在儿童健康与发展研究中开展了一项病例对照研究,该研究是一个出生队列,于1959年至1966年招募了孕妇。通过电子病历、公共机构数据库以及向该队列邮寄调查问卷,确定了符合《精神疾病诊断与统计手册》第四版修订版(DSM-IV-TR)中双相I型障碍、双相II型障碍、未特定型双相情感障碍以及伴有精神病性特征的双相情感障碍的潜在病例。诊断通过临床访谈得以确认。通过Luminex检测法同时检测了85例病例和170例匹配对照的存档产前母体血清样本中的9种细胞因子(IL-1β、IL-4、IL-5、IL-6、IL-8、IL-10、IFN-γ、TNF-α和GM-CSF)。使用条件逻辑回归分析数据。在整个研究样本中,调整混杂因素后,产前母体细胞因子水平与双相情感障碍之间无显著关联。在孕早期经对数转换的IL-4母体水平较高(OR(95%CI)=0.76(0.58,0.98);p=0.04)以及孕晚期经对数转换的IL-6母体水平较高(OR(95%CI)=0.64(0.42,0.98);p=0.04)的受试者中,无精神病性特征的双相情感障碍风险降低。总之,产前母体细胞因子水平较高与双相情感障碍风险增加无关。需要进一步开展更大样本量的研究来证实这一发现。