title: COMT haplotypes modulate associations of antenatal maternal anxiety and neonatal cortical morphology.
abstract: OBJECTIVE
  Exposure to antenatal maternal anxiety and complex genetic variations may shape fetal brain development. In particular, the catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11.2, regulates catecholamine signaling in the prefrontal cortex and is implicated in anxiety, pain, and stress responsivity. This study examined whether individual single-nucleotide polymorphisms (SNPs) of the COMT gene and their haplotypes moderate the association between antenatal maternal anxiety and in utero cortical development.
  
  
  METHODS
  A total of 146 neonates were genotyped and underwent MRI shortly after birth. Neonatal cortical morphology was characterized using cortical thickness. Antenatal maternal anxiety was assessed using the State-Trait Anxiety Inventory at week 26 of pregnancy.
  
  
  RESULTS
  Individual COMT SNPs (val158met, rs737865, and rs165599) modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Based on haplotype trend regression analysis, findings also showed that among rs737865-val158met-rs165599 haplotypes, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus. In contrast, the G-met-A (GAA) haplotype probabilities modulated negative associations of antenatal maternal anxiety with cortical thickness in bilateral precentral gyrus and the dorsolateral prefrontal cortex.
  
  
  CONCLUSIONS
  These results suggest that the association between maternal anxiety and in utero neurodevelopment is modified through complex genetic variation in COMT. Such genetic moderation may explain, in part, the variation in phenotypic outcomes in offspring associated with maternal emotional well-being.
authors.affiliation: From the Department of Biomedical Engineering and Clinical Imaging Research Center, National University of Singapore, Singapore; the Singapore Institute for Clinical Sciences, Singapore; the Department of Diagnostic and Interventional Imaging, KK Women's and Children's Hospital, Singapore; the Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore; the Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal; the Sackler Program for Epigenetics and Psychobiology at McGill University, Montreal; the Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore; the KK Women's and Children's Hospital, Singapore; and the Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Anqi
authors.initials: A
authors.lastname: Qiu
authors.forename: Ta Anh
authors.initials: TA
authors.lastname: Tuan
authors.forename: Mei Lyn
authors.initials: ML
authors.lastname: Ong
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Helen
authors.initials: H
authors.lastname: Chen
authors.forename: Anne
authors.initials: A
authors.lastname: Rifkin-Graboi
authors.forename: Birit F P
authors.initials: BF
authors.lastname: Broekman
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kwek
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
authors.forename: Yap-Seng
authors.initials: YS
authors.lastname: Chong
authors.forename: Peter D
authors.initials: PD
authors.lastname: Gluckman
authors.forename: Marielle V
authors.initials: MV
authors.lastname: Fortier
authors.forename: Joanna Dawn
authors.initials: JD
authors.lastname: Holbrook
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
mesh_terms: D001007:Anxiety / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D033261:Maternal-Fetal Relations; D010296:Parietal Lobe / Q000254:growth & development / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000254:growth & development / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D011297:Prenatal Exposure Delayed Effects; D011569:Psychiatric Status Rating Scales; D012846:Singapore
chemical_list: D002394:Catechol O-Methyltransferase