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Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors

Published online by Cambridge University Press:  22 June 2015

K. Räikkönen ,
A.-K. Pesonen ,
J. R. O'Reilly ,
S. Tuovinen ,
M. Lahti ,
E. Kajantie ,
P. Villa ,
H. Laivuori ,
E. Hämäläinen  and
J. R. Seckl
...Show all authors
K. Räikkönen*
Affiliation:
Institute of Behavioral Sciences, University of Helsinki, Helsinki, Finland
A.-K. Pesonen
Affiliation:
Institute of Behavioral Sciences, University of Helsinki, Helsinki, Finland
J. R. O'Reilly
Affiliation:
Endocrinology Unit, University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh, UK
S. Tuovinen
Affiliation:
Institute of Behavioral Sciences, University of Helsinki, Helsinki, Finland
M. Lahti
Affiliation:
Institute of Behavioral Sciences, University of Helsinki, Helsinki, Finland
E. Kajantie
Affiliation:
National Institute for Health and Welfare, Helsinki, Finland Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland Helsinki University Central Hospital and University of Helsinki, University of Helsinki, Helsinki, Finland
P. Villa
Affiliation:
Research Programmes Unit, Women's Health, University of Helsinki, Helsinki, Finland Department of Obstetrics and Gynaecology (PV), University of Helsinki and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
H. Laivuori
Affiliation:
Haartman Institute, Medical Genetics, University of Helsinki, Helsinki, Finland
E. Hämäläinen
Affiliation:
HUSLAB and Department of Clinical Chemistry, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
J. R. Seckl
Affiliation:
Endocrinology Unit, University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh, UK
R. M. Reynolds
Affiliation:
Endocrinology Unit, University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh, UK
*
* Address for correspondence: Professor K. Räikkönen, Institute of Behavioral Sciences, P.O Box 9 (Siltavuorenpenger 1 A), 00014 University of Helsinki, 00029 Helsinki, Finland. (Email: katri.raikkonen@helsinki.fi)
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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.

Method.

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.

Keywords

BehaviourinfantmothermRNAplacentapregnancyprospective
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 15 , November 2015 , pp. 3217 - 3226
Copyright
Copyright © Cambridge University Press 2015 

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