Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring.
OBJECTIVE
Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection and in other inflammatory processes. The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 (IL-8), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects.


METHODS
The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort, born 1959-1967. Cases (N=59) were subjects diagnosed with schizophrenia spectrum disorders (mostly schizophrenia and schizoaffective disorder) who had available second-trimester maternal serum samples. Comparison subjects (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder, and were matched to subjects with schizophrenia for date of birth, gender, length of time in the cohort, and availability of maternal sera. Maternal second-trimester serum levels of IL-8, IL-1beta, IL-6, and TNF-alpha were determined by sandwich enzyme-linked immunosorbent assay.


RESULTS
The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects. There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta, IL-6, or TNF-alpha.


CONCLUSIONS
Using prospectively collected prenatal sera in a large and well-characterized birth cohort, the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring. These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia. Moreover, these results may have important implications for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder.
Brown
Alan S
AS
New York State Psychiatric Institute, 1051 Riverside Dr., Unit 2, New York, NY 10032, USA. asb11@columbia.edu
Hooton
Jonathan
J
Schaefer
Catherine A
CA
Zhang
Haiying
H
Petkova
Eva
E
Babulas
Vicki
V
Perrin
Megan
M
Gorman
Jack M
JM
Susser
Ezra S
ES
D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000276:immunology; D011262:Pregnancy Trimester, Second / Q000097:blood* / Q000276:immunology; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha