title: Maternal serum cytokine levels and risk of bipolar disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, United States. Electronic address: kc2497@cumc.columbia.edu.
authors.forename: Keely
authors.initials: K
authors.lastname: Cheslack-Postava
authors.affiliation: Pathology and Cell Biology, Columbia University Medical Center, New York, NY, United States.
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, United States.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Bao
authors.affiliation: KPNC Permanente Division of Research, Oakland, CA, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: KPNC Permanente Division of Research, Oakland, CA, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schaefer
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, United States; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, United States.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Brown
mesh_terms: D001714:Bipolar Disorder / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007251:Influenza, Human / Q000150:complications; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D015847:Interleukin-4
keywords: Bipolar disorder; Cytokines; IL-4; IL-6; Immune; Maternal; Prenatal