title: Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors.
abstract: BACKGROUND
  Glucocorticoids and serotonin may mediate the link between maternal environment, fetal brain development and 'programming' of offspring behaviors. The placenta regulates fetal exposure to maternal hormonal signals in animal studies, but few data address this in humans. We measured prospectively maternal depressive symptoms during pregnancy and mRNAs encoding key gene products determining glucocorticoid and serotonin function in term human placenta and explored associations with infant regulatory behaviors.
  
  
  METHODS
  Bi-weekly self-ratings of the Center for Epidemiologic Studies Depression Scale from 12th to 13th gestational week onwards and term placental mRNAs of 11beta-hydroxysteroid dehydrogenase type 2 (HSD2B11), type 1 (HSD1B11), glucocorticoid (NR3C1), mineralocorticoid receptors (NR3C2) and serotonin transporter (SLC6A4) were obtained from 54 healthy mothers aged 32.2 ± 5.3 years with singleton pregnancies and without pregnancy complications. Infant regulatory behaviors (crying, feeding, spitting, elimination, sleeping and predictability) were mother-rated at 15.6 ± 4.2 days.
  
  
  RESULTS
  Higher placental mRNA levels of HSD2B11 [0.41 standard deviation (s.d.) unit increase per s.d. unit increase; 95% confidence interval (CI) 0.13-0.69, p = 0.005], HSD1B11 (0.30, 0.03-0.57, p = 0.03), NR3C1 (0.44, 0.19-0.68, p = 0.001) and SLC6A4 (0.26, 0.00-0.53, p = 0.05) were associated with more regulatory behavioral challenges of the infant. Higher placental NR3C1 mRNA partly mediated the association between maternal depressive symptoms during pregnancy and infant regulatory behaviors (p < 0.05).
  
  
  CONCLUSIONS
  Higher placental expression of genes regulating feto-placental glucocorticoid and serotonin exposure is characteristic of infants with more regulatory behavioral challenges. Maternal depression acts, at least partly, via altering glucocorticoid action in the placenta to impact on offspring regulatory behaviors.
authors.affiliation: Institute of Behavioral Sciences,University of Helsinki,Helsinki,Finland.
authors.forename: K
authors.initials: K
authors.lastname: Räikkönen
authors.affiliation: Institute of Behavioral Sciences,University of Helsinki,Helsinki,Finland.
authors.forename: A-K
authors.initials: AK
authors.lastname: Pesonen
authors.affiliation: Endocrinology Unit,University/BHF Centre for Cardiovascular Science,Queen's Medical Research Institute,Edinburgh,UK.
authors.forename: J R
authors.initials: JR
authors.lastname: O'Reilly
authors.affiliation: Institute of Behavioral Sciences,University of Helsinki,Helsinki,Finland.
authors.forename: S
authors.initials: S
authors.lastname: Tuovinen
authors.affiliation: Institute of Behavioral Sciences,University of Helsinki,Helsinki,Finland.
authors.forename: M
authors.initials: M
authors.lastname: Lahti
authors.affiliation: National Institute for Health and Welfare,Helsinki,Finland.
authors.forename: E
authors.initials: E
authors.lastname: Kajantie
authors.affiliation: Research Programmes Unit,Women's Health,University of Helsinki,Helsinki,Finland.
authors.forename: P
authors.initials: P
authors.lastname: Villa
authors.affiliation: Haartman Institute,Medical Genetics,University of Helsinki,Helsinki,Finland.
authors.forename: H
authors.initials: H
authors.lastname: Laivuori
authors.affiliation: HUSLAB and Department of Clinical Chemistry,Helsinki University Central Hospital, University of Helsinki,Helsinki,Finland.
authors.forename: E
authors.initials: E
authors.lastname: Hämäläinen
authors.affiliation: Endocrinology Unit,University/BHF Centre for Cardiovascular Science,Queen's Medical Research Institute,Edinburgh,UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Seckl
authors.affiliation: Endocrinology Unit,University/BHF Centre for Cardiovascular Science,Queen's Medical Research Institute,Edinburgh,UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D003863:Depression / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D005938:Glucocorticoids / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D018730:Infant Behavior / Q000502:physiology*; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D000066553:Problem Behavior; D012333:RNA, Messenger / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin
keywords: Behaviour; infant; mRNA; mother; placenta; pregnancy; prospective