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


CONCLUSIONS
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.
Ellman
Lauren M
LM
Department of Psychology, Temple University, Philadelphia, PA 19122-6085, United States. ellman@temple.edu
Deicken
Raymond F
RF
Vinogradov
Sophia
S
Kremen
William S
WS
Poole
John H
JH
Kern
David M
DM
Tsai
Wei Yann
WY
Schaefer
Catherine A
CA
Brown
Alan S
AS
D000328:Adult; D001921:Brain / Q000254:growth & development / Q000473:pathology*; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D016209:Interleukin-8 / Q000009:adverse effects* / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D011297:Prenatal Exposure Delayed Effects / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000473:pathology*; D012559:Schizophrenia / Q000188:drug therapy
D016207:Cytokines; D016209:Interleukin-8