Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8

Lauren M. Ellman, Raymond F. Deicken, Sophia Vinogradov, William S. Kremen, John H. Poole, David M. Kern, Wei Yann Tsai, Catherine A. Schaefer, Alan S. Brown

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

Abstract

Background: Maternal infection during pregnancy has been repeatedly associated with increased risk for schizophrenia. Nevertheless, most viruses do not cross the placenta; therefore, the damaging effects to the fetus appear to be related to maternal antiviral responses to infection (e.g. proinflammatory cytokines). Fetal exposure to the proinflammatory cytokine interleukin-8 (IL-8) has been significantly associated with risk of schizophrenia in offspring. This study sought to determine the association between fetal exposure to IL-8 and structural brain changes among schizophrenia cases and controls. Methods: Subjects were 17 cases diagnosed with schizophrenia from the Developmental Insult and Brain Anomaly in Schizophrenia (DIBS) study. Psychiatric diagnoses were determined among offspring with semi-structured interviews and medical records review. IL-8 was determined from assays in archived prenatal sera and volumetric analyses of neuroanatomical regions were obtained from T1-weighted magnetic resonance imaging in adulthood. Eight controls were included for exploratory purposes. Results: Among cases, fetal exposure to increases in IL-8 was associated with significant increases in ventricular cerebrospinal fluid, significant decreases in left entorhinal cortex volumes and significant decreases in right posterior cingulate volumes. Decreases that approached significance also were found in volumes of the right caudate, the putamen (bilaterally), and the right superior temporal gyrus. No significant associations were observed among controls. Conclusion: Fetal exposure to elevations in maternal IL-8 led to structural neuroanatomic alterations among cases in regions of the brain consistently implicated in schizophrenia research. In utero exposure to elevations in IL-8 may partially account for brain disturbances commonly found in schizophrenia.

Original languageEnglish (US)
Pages (from-to)46-54
Number of pages9
JournalSchizophrenia Research
Volume121
Issue number1-3
DOIs
StatePublished - Aug 2010

Bibliographical note

Funding Information:
This study was supported by research grants to Dr. Brown from the National Institute of Mental Health ( R01MH060249 , R01MH63264 , and K02 MH065422-06 ) and a postdoctoral NIMH schizophrenia research fellowship to Dr. Ellman ( 5 T32 MH018870-20 ) and grants N01HD13334 and N01HD63258 from The Eunice Kennedy Shriver Institute of Child Health and Human Development . We also thank Theo van Erp, Ezra Susser, Michaeline Bresnahan, Barbara Cohn, Nashid Chaudhury, Aundrea Cook, Justin Penner, Nicole Stephenson, Dawn Schpak and the study teams of the CHDS, the PDS, and the DIBS for their contributions to data collection and preparation of this manuscript. The authors also wish to acknowledge Larry Kegeles, M.D. for his helpful comments.

Funding Information:
This study was supported by research grants to Dr. Brown from the National Institute of Mental Health (R01MH060249, R01MH63264, and K02 MH065422-06) and a postdoctoral NIMH schizophrenia research fellowship to Dr. Ellman (5 T32 MH018870-20) and grants N01HD13334 and N01HD63258 from The Eunice Kennedy Shriver Institute of Child Health and Human Development. These funding sources had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Keywords

  • Infection
  • Obstetric complications
  • Pregnancy
  • Proinflammatory cytokines
  • Schizophrenia
  • Structural MRI

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