TY - JOUR
T1 - Inflammatory modulation of the associations between prenatal maternal depression and neonatal brain
AU - Wu, Yonghui
AU - Zhang, Han
AU - Wang, Changqing
AU - Broekman, Birit F.P.
AU - Chong, Yap Seng
AU - Shek, Lynette P.
AU - Gluckman, Peter D.
AU - Meaney, Michael J.
AU - Fortier, Marielle V.
AU - Qiu, Anqi
N1 - Funding Information: This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore-NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore Ministry of Education (Academic research fund tier 1; NUHSRO/ 2017/052/T1-SRP-Partnership/01), and NUS Institute of Data Science, Singapore. The authors declare no competing interests. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Inflammatory signaling has a role in sensing intrauterine environment, which may be moderators in altering fetal brain development upon maternal environment. This study integrated cytokine transcriptome of post-mortem fetal brains, neonatal brain imaging and genetic variants (n = 161) to examine whether cytokines are candidates for modulating the relationship between prenatal maternal depression and fetal brain development. This study obtained the transcriptome data of 208 cytokine genes in 12 fetal brain regions from the BrainSpan database. We also included 161 mother–child dyads with prenatal maternal depressive symptoms assessed at 26 weeks of gestation, cytokine genotype data extracted from umbilical cord specimens, and neonatal brain images from a longitudinal prospective birth cohort. We revealed that 22 cytokine genes are expressed in specific brain regions in utero, whose variants have roles in modulating the effects of the prenatal environment on the accelerated fetal development of the hippocampus, auditory, parietal, orbitofrontal, and dorsal prefrontal cortex. Neonates high in the genetic expression score (GES) of TNFRSF19 and IL17RB showed a larger right hippocampal volume, high in the GES of BMPR1B showed the thicker thickness of the sensorimotor cortex, and high in the GES of IL1RAP and CXCR4 demonstrated the thicker thickness of the dorsal and orbital prefrontal cortex in relation with greater prenatal maternal depressive symptoms. Our findings suggest that in humans, the cytokine genes are expressed in a brain region-specific manner in utero and may have potential roles in modulating the fetal development of the corresponding brain regions in response to the maternal environment.
AB - Inflammatory signaling has a role in sensing intrauterine environment, which may be moderators in altering fetal brain development upon maternal environment. This study integrated cytokine transcriptome of post-mortem fetal brains, neonatal brain imaging and genetic variants (n = 161) to examine whether cytokines are candidates for modulating the relationship between prenatal maternal depression and fetal brain development. This study obtained the transcriptome data of 208 cytokine genes in 12 fetal brain regions from the BrainSpan database. We also included 161 mother–child dyads with prenatal maternal depressive symptoms assessed at 26 weeks of gestation, cytokine genotype data extracted from umbilical cord specimens, and neonatal brain images from a longitudinal prospective birth cohort. We revealed that 22 cytokine genes are expressed in specific brain regions in utero, whose variants have roles in modulating the effects of the prenatal environment on the accelerated fetal development of the hippocampus, auditory, parietal, orbitofrontal, and dorsal prefrontal cortex. Neonates high in the genetic expression score (GES) of TNFRSF19 and IL17RB showed a larger right hippocampal volume, high in the GES of BMPR1B showed the thicker thickness of the sensorimotor cortex, and high in the GES of IL1RAP and CXCR4 demonstrated the thicker thickness of the dorsal and orbital prefrontal cortex in relation with greater prenatal maternal depressive symptoms. Our findings suggest that in humans, the cytokine genes are expressed in a brain region-specific manner in utero and may have potential roles in modulating the fetal development of the corresponding brain regions in response to the maternal environment.
UR - http://www.scopus.com/inward/record.url?scp=85088252292&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41386-020-0774-0
DO - https://doi.org/10.1038/s41386-020-0774-0
M3 - Article
C2 - 32688365
SN - 0893-133X
VL - 46
SP - 470
EP - 477
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 2
ER -