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Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity

  • R. M. Reynolds (a1), A.-K. Pesonen (a2), J. R. O'Reilly (a1), S. Tuovinen (a2), M. Lahti (a2), E. Kajantie (a3) (a4) (a5), P. M. Villa (a6), H. Laivuori (a7), E. Hämäläinen (a8), J. R. Seckl (a1) and K. Räikkönen (a2)...
Abstract
Background

Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus.

Method

We studied women participating in a prospective pregnancy cohort: the Prediction and Prevention of Preeclampsia (PREDO) Study, Helsinki, Finland. Maternal depressive symptoms were assessed at 2-week intervals throughout pregnancy in 56 healthy women with singleton, term pregnancies. Messenger ribonucleic acid (mRNA) levels of glucocorticoid (GR) and mineralocorticoid (MR) receptors and serotonin transporter (SLC6A4), 11β-hydroxysteroid dehydrogenase type 1 (HSD1) and 2 (HSD2) were quantified in placental biopsies.

Results

In adjusted analyses women who reported higher depressive symptoms across the whole pregnancy had higher mRNA levels of GR [effect size 0.31 s.d. units, 95% confidence interval (CI) 0.01–0.60, p = 0.042] and MR (effect size 0.34 s.d. units, 95% CI 0.01–0.68, p = 0.047). These effects were significant for symptoms experienced in the third trimester of pregnancy for GR; findings for MR were also significant for symptoms experienced in the second trimester. GR and MR mRNA levels increased linearly by having the trimester-specific depressive symptoms scores 0, 1 or 2–3 times above the clinical cut-off for depression (p = 0.003, p = 0.049, respectively, and p = 0.004, p = 0.15 in adjusted analyses).

Conclusions

Our findings offer potential gestational-age-specific mechanisms linking maternal depressive symptoms during pregnancy via placental biology. Future studies will test whether these also link with adverse offspring outcomes.

Copyright
Corresponding author
* Address for correspondence: R. Reynolds, Endocrinology Unit, BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK. (Email: R.Reynolds@ed.ac.uk)
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A Bonnin , N Goeden , K Chen , ML Wilson , J King , JC Shih , RD Blakely , ES Deneri , P Levitt (2011). A transient placental source of serotonin for the fetal forebrain. Nature 472, 347350.

E Conradt , BM Lester , AA Appleton , DA Armstrong , CJ Marsit (2013). The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn behaviour. Epigenetics 8, 13211329.

EC Cottrell , JR Seckl (2009). Prenatal stress, glucocorticoids and the programming of adult disease. Frontiers in Behavioural Neuroscience 3, 19.

AM Devlin , U Brain , J Austin , TF Oberlander (2010). Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth. PLoS ONE 5, e12201.

CRW Edwards , R Benediktsson , R Lindsay , JR Seckl (1993). Dysfunction of the placental glucocorticoid barrier: a link between the foetal environment and adult hypertension? Lancet 341, 355357.

T Field (2011). Prenatal depression effects on early development: a review. Infant Behaviour and Development 34, 114.

T Field , M Diego , J Dieter , M Hernandez-Reif (2006). Prenatal depression effects on the fetus and the newborn: a review. Infant Behaviour and Development 29, 445455.

T Field , MA Diego , M Hernandez-Reif , B Figueiredo , A Ascencio , S Schanberg , C Kuhn (2008). Prenatal dysthymia versus major depression effects on maternal cortisol and fetal growth. Depression and Anxiety 25, E1.

IH Gotlib , J Joorman , KL Minor , J Hallmayer (2008). HPA axis reactivity: a mechanism underlying the associations among serotonin TLPR stress, and depression. Biological Psychiatry 63, 847851.

K Hogg , EM Price , CW Hanna , WP Robinson (2012). Prenatal and perinatal environmental influences on the human fetal and placental epigenome. Clinical Pharmacology and Therapeutics 92, 716726.

T Hompes , B Izzi , E Gellens , M Morreels , S Fieuws , A Pexsters , G Schops , M Dom , R Van Bree , K Freson , J Verhaeghe , B Spitz , K Demyttenaere , V Glover , B Van den Bergh , K Allegaert , S Claes (2013). Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. Journal of Psychiatric Research 47, 880891.

VE Murphy , R Smith , WB Giles , VL Clifton (2006). Endocrine regulation of human fetal growth: the role of the mother, placenta and fetus. Endocrine Reviews 27, 141169.

I Nast , M Bolten , G Meinlschmidt , DH Hellhammer (2013). How to measure prenatal stress? A systematic review of psychometric instruments to assess psychosocial stress during pregnancy. Paediatric and Perinatal Epidemiology 27, 313322.

B Novakovic , R Saffery (2012). The ever growing complexity of placental epigenetics – role in adverse pregnancy outcomes and fetal programming. Placenta 33, 959970.

TF Oberlander , J Weinberg , M Papsdorf , R Grunau , S Misri , AM Devlin (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3, 97106.

K O'Donnell , TG O'Connor , V Glover (2009). Prenatal stress and neurodevelopment of the child: focus on the HPA axis and role of the placenta. Developmental Neuroscience 31, 285292.

KJ O'Donnell , A Bugge Jensen , L Freeman , N Khalife , TG O'Connor , V Glover (2012). Maternal prenatal anxiety and downregulation of placental 11β-HSD2. Psychoneuroendocrinology 37, 818826.

V O'Keane , S Lightman , M Marsh , S Pawlby , AS Papadopoulos , A Taylor , R Moore , K Patrick (2011). Increased pituitary–adrenal activation and shortened gestation in a sample of depressed pregnant women: a pilot study. Journal of Affective Disorders 130, 300305.

JD Olivier , H Akerud , H Kaihola , JL Pawluski , A Skalkidou , U Högberg , I Sundström-Poromaa (2013). The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring. Frontiers in Cellular Neuroscience 7, 73.

KL Ponder , A Salisbury , B McGonnigal , A Laliberte , B Lester , JF Padbury (2011). Maternal depression and anxiety are associated with altered gene expression in the human placenta without modification by antidepressant use: implications for fetal programming. Developmental Psychobiology 53, 711723.

L Radloff (1977). The CES-D Scale: a self-report symptom scale to detect depression in a community sample. Applied Psychological Measurement 1, 385401.

K Räikkönen , JR O'Reilly , A-K Pesonen , E Kajantie , P Villa , H Laivuori , E Hämäläinen , JR Seckl , RM Reynolds (2014). Lower maternal socioeconomic status is associated with increased placental glucocorticoid regeneration and sensitivity. Clinical Endocrinology 81, 175182.

K Räikkönen , AK Pesonen , TJ Roseboom , JG Eriksson (2012). Early determinants of mental health. Best Practice and Research Clinical Endocrinology and Metabolism 26, 599611.

KJ Ressler , CB Nemeroff (2000). Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and Anxiety 12, 219.

RM Reynolds , GH Jacobsen , AJ Drake (2013). What is the evidence in humans that DNA methylation changes link events in utero and later life disease? Clinical Endocrinology 78, 814822.

JW Rich-Edwards , AP Mohllajee , K Kleinman , MR Hacker , J Majzoub , RJ Wright , MW Gillman (2008). Elevated midpregnancy corticotropin-releasing hormone is associated with prenatal, but not postpartum, maternal depression. Journal of Clinical Endocrinology and Metabolism 93, 19461951.

JC Velasquez , N Goeden , A Bonnin (2013). Placental serotonin: implications for the developmental effects of SSRIs and maternal depression. Frontiers in Cellular Neuroscience 7, 47.

P Villa , E Kajantie , K Räikkönen , AK Pesonen , E Hämäläinen , M Vainio , P Taipale , H Laivuori , The Predo Study Group (2013). Aspirin in the prevention of pre-eclampsia in high-risk women: a randomized placebo-controlled PREDO Trial. British Journal of Obstetrics and Gynaecology 120, 6474.

CS Wyrwoll , MC Holmes (2012). Prenatal excess glucocorticoid exposure and adult affective disorders: a role for serotonergic and catecholamine pathways. Neuroendocrinology 95, 4755.

R Yehuda , SM Engel , SR Brand , J Seckl , SM Marcus , GS Berkowitz (2005). Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. Journal of Clinical Endocrinology and Metabolism 90, 41154118.

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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
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