Skip to main content
×
Home
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 11
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Schiller, Crystal Edler Meltzer-Brody, Samantha and Rubinow, David R. 2015. The role of reproductive hormones in postpartum depression. CNS Spectrums, Vol. 20, Issue. 01, p. 48.


    Serati, M. Redaelli, M. Buoli, M. and Altamura, A.C. 2016. Perinatal Major Depression Biomarkers: A systematic review. Journal of Affective Disorders, Vol. 193, p. 391.


    Breen, Michael S. Stein, Dan J. and Baldwin, David S. 2016. Systematic review of blood transcriptome profiling in neuropsychiatric disorders: guidelines for biomarker discovery. Human Psychopharmacology: Clinical and Experimental, Vol. 31, Issue. 5, p. 373.


    Curley, Maureen 2014. An Explanatory Model to Guide Assessment, Risk and Diagnosis of Psychological Distress after Abortion. Open Journal of Obstetrics and Gynecology, Vol. 04, Issue. 15, p. 944.


    Osborne, Lauren Clive, Makena Kimmel, Mary Gispen, Fiona Guintivano, Jerry Brown, Tori Cox, Olivia Judy, Jennifer Meilman, Samantha Braier, Aviva Beckmann, Matthias W Kornhuber, Johannes Fasching, Peter A Goes, Fernando Payne, Jennifer L Binder, Elisabeth B and Kaminsky, Zachary 2016. Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels. Neuropsychopharmacology, Vol. 41, Issue. 6, p. 1648.


    Freitas, Cassidy J. and Fox, Curtis A. 2015. Fathers Matter: Family Therapy’s Role in the Treatment of Paternal Peripartum Depression. Contemporary Family Therapy, Vol. 37, Issue. 4, p. 417.


    Tan, Ene-Choo Chua, Tze-Ern Lee, Theresa M. Y. Tan, Hui-San Ting, Joe L. Y. and Chen, Helen Y. 2015. Case-control study of glucocorticoid receptor and corticotrophin-releasing hormone receptor gene variants and risk of perinatal depression. BMC Pregnancy and Childbirth, Vol. 15, Issue. 1,


    Henningsson, S Madsen, K H Pinborg, A Heede, M Knudsen, G M Siebner, H R and Frokjaer, V G 2015. Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study. Translational Psychiatry, Vol. 5, Issue. 12, p. e688.


    Kim, Kiwon Hong, Jin Pyo Cho, Maeng Je Fava, Maurizio Mischoulon, David Lee, Dong-Woo Heo, Jung-Yoon and Jeon, Hong Jin 2016. Loss of sexual interest and premenstrual mood change in women with postpartum versus non-postpartum depression: A nationwide community sample of Korean adults. Journal of Affective Disorders, Vol. 191, p. 222.


    Wankerl, M Miller, R Kirschbaum, C Hennig, J Stalder, T and Alexander, N 2014. Effects of genetic and early environmental risk factors for depression on serotonin transporter expression and methylation profiles. Translational Psychiatry, Vol. 4, Issue. 6, p. e402.


    O’Connor, Thomas G. Monk, Catherine and Burke, Anne S. 2016. Maternal Affective Illness in the Perinatal Period and Child Development: Findings on Developmental Timing, Mechanisms, and Intervention. Current Psychiatry Reports, Vol. 18, Issue. 3,


    ×

Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling

  • D. Mehta (a1), D. J. Newport (a2), G. Frishman (a3), L. Kraus (a1), M. Rex-Haffner (a1), J. C. Ritchie (a4), A. Lori (a5), B. T. Knight (a6), E. Stagnaro (a2), A. Ruepp (a3), Z. N. Stowe (a6) and E. B. Binder (a1) (a2)
  • DOI: http://dx.doi.org/10.1017/S0033291713003231
  • Published online: 31 January 2014
Abstract
Background

Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort.

Method

We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R.

Results

We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD.

Conclusions

These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.

Copyright
Corresponding author
*Address for correspondence: E. B. Binder, M.D., Max Planck Institute of Psychiatry, Kraepelinstrasse 2, Munich 80804, Germany. (Email: binder@mpipsykl.mpg.de) [E. B. Binder] (Email: mehta@mpipsykl.mpg.de) [D. Mehta]
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

G Albacar , T Sans , R Martin-Santos , L Garcia-Esteve , R Guillamat , J Sanjuan , F Canellas , JM Carot , M Gratacos , J Bosch , A Gaviria , A Labad , AG Zotes , E Vilella (2010). Thyroid function 48 h after delivery as a marker for subsequent postpartum depression. Psychoneuroendocrinology 35, 738742.

KM Bailara , C Henry , J Lestage , JM Launay , F Parrot , J Swendsen , AL Sutter , D Roux , D Dallay , J Demotes-Mainard (2006). Decreased brain tryptophan availability as a partial determinant of post-partum blues. Psychoneuroendocrinology 31, 407413.

CT Beck (1998). The effects of postpartum depression on child development: a meta-analysis. Archives of Psychiatric Nursing 12, 1220.

HA Bennett , A Einarson , A Taddio , G Koren , TR Einarson (2004). Depression during pregnancy : overview of clinical factors. Clinical Drug Investigation 24, 157179.

M Bloch , I Aharonov , I Ben Avi , S Schreiber , A Amit , A Weizman , F Azem (2011). Gonadal steroids and affective symptoms during in vitro fertilization: implication for reproductive mood disorders. Psychoneuroendocrinology 36, 790796.

M Bloch , N Rotenberg , D Koren , E Klein (2005). Risk factors associated with the development of postpartum mood disorders. Journal of Affective Disorders 88, 918.

M Bloch , N Rotenberg , D Koren , E Klein (2006). Risk factors for early postpartum depressive symptoms. General Hospital Psychiatry 28, 38.

M Bloch , PJ Schmidt , M Danaceau , J Murphy , L Nieman , DR Rubinow (2000). Effects of gonadal steroids in women with a history of postpartum depression. American Journal of Psychiatry 157, 924930.

PA Brennan , R Pargas , EF Walker , P Green , DJ Newport , Z Stowe (2008). Maternal depression and infant cortisol: influences of timing, comorbidity and treatment. Journal of Child Psychology and Psychiatry 49, 10991107.

HE Covington 3rd, V Vialou , EJ Nestler (2009). From synapse to nucleus: novel targets for treating depression. Neuropharmacology 58, 683693.

N Craddock , L Forty (2006). Genetics of affective (mood) disorders. European Journal of Human Genetics 14, 660668.

D Deecher , TH Andree , D Sloan , LE Schechter (2008). From menarche to menopause: exploring the underlying biology of depression in women experiencing hormonal changes. Psychoneuroendocrinology 33, 317.

FN Demetrio , J Renno Jr, A Gianfaldoni , M Goncalves , HW Halbe , AH Filho , C Gorenstein (2011). Effect of estrogen replacement therapy on symptoms of depression and anxiety in non-depressive menopausal women: a randomized double-blind, controlled study. Archives of Women's Mental Health 14, 479486.

WC Drevets , ME Thase , EL Moses-Kolko , J Price , E Frank , DJ Kupfer , C Mathis (2007). Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nuclear Medicine and Biology 34, 865877.

MJ Essex , MH Klein , E Cho , NH Kalin (2002). Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior. Biological Psychiatry 52, 776784.

L Forty , L Jones , S Macgregor , S Caesar , C Cooper , A Hough , L Dean , S Dave , A Farmer , P McGuffin , S Brewster , N Craddock , I Jones (2006). Familiality of postpartum depression in unipolar disorder: results of a family study. American Journal of Psychiatry 163, 15491553.

CC Hsiao , CY Liu , MC Hsiao (2004). No correlation of depression and anxiety to plasma estrogen and progesterone levels in patients with premenstrual dysphoric disorder. Psychiatry and Clinical Neurosciences 58, 593599.

A Inoue , N Yoshida , Y Omoto , S Oguchi , T Yamori , R Kiyama , S Hayashi (2002). Development of cDNA microarray for expression profiling of estrogen-responsive genes. Journal of Molecular Endocrinology 29, 175192.


KS Kendler , MC Neale , RC Kessler , AC Heath , LJ Eaves (1992). A population-based twin study of major depression in women. The impact of varying definitions of illness. Archives of General Psychiatry 49, 257266.

RC Kessler , EE Walters (1998). Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the National Comorbidity Survey. Depression and Anxiety 7, 314.

V Krishnan , EJ Nestler (2010). Linking molecules to mood: new insight into the biology of depression. American Journal of Psychiatry 167, 13051320.

JL Kuijpens , HL Vader , HA Drexhage , WM Wiersinga , MJ van Son , VJ Pop (2001). Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum. European Journal of Endocrinology 145, 579584.

BM Leung , BJ Kaplan (2009). Perinatal depression: prevalence, risks, and the nutrition link – a review of the literature. Journal of the American Dietetic Association 109, 15661575.

S Lokuge , BN Frey , JA Foster , CN Soares , M Steiner (2011). Depression in women: windows of vulnerability and new insights into the link between estrogen and serotonin. Journal of Clinical Psychiatry 72, e1563e1569.

M Lommatzsch , K Hornych , C Zingler , P Schuff-Werner , J Hoppner , JC Virchow (2006). Maternal serum concentrations of BDNF and depression in the perinatal period. Psychoneuroendocrinology 31, 388394.

M Maes , W Ombelet , R Verkerk , E Bosmans , S Scharpe (2001). Effects of pregnancy and delivery on the availability of plasma tryptophan to the brain: relationships to delivery-induced immune activation and early post-partum anxiety and depression. Psychological Medicine 31, 847858.

M Maes , R Verkerk , S Bonaccorso , W Ombelet , E Bosmans , S Scharpe (2002). Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation. Life Sciences 71, 18371848.

M McCarthy , C McMahon (2008). Acceptance and experience of treatment for postnatal depression in a community mental health setting. Health Care for Women International 29, 618637.

D Mehta , M Gonik , T Klengel , M Rex-Haffner , A Menke , J Rubel , KB Mercer , B Putz , B Bradley , F Holsboer , KJ Ressler , B Muller-Myhsok , EB Binder (2011). Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies. Archives of General Psychiatry 68, 901910.

C Mitchell , D Notterman , J Brooks-Gunn , J Hobcraft , I Garfinkel , K Jaeger , I Kotenko , S McLanahan (2011). Role of mother's genes and environment in postpartum depression. Proceedings of the National Academy of Sciences USA 108, 81898193.

RC Ng , CK Hirata , W Yeung , E Haller , PR Finley (2010). Pharmacologic treatment for postpartum depression: a systematic review. Pharmacotherapy 30, 928941.

TG O'Connor , P Caprariello , ER Blackmore , AM Gregory , V Glover , P Fleming (2007). Prenatal mood disturbance predicts sleep problems in infancy and toddlerhood. Early Human Development 83, 451458.

MW O'Hara , JA Schlechte , DA Lewis , MW Varner (1991). Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables. Journal of Abnormal Psychology 100, 6373.

S Pawlby , DF Hay , D Sharp , CS Waters , V O'Keane (2009). Antenatal depression predicts depression in adolescent offspring: prospective longitudinal community-based study. Journal of Affective Disorders 113, 236243.

AM Quelopana , JD Champion , T Reyes-Rubilar (2011). Factors associated with postpartum depression in Chilean women. Health Care for Women International 32, 939949.

A Rahman , Z Iqbal , J Bunn , H Lovel , R Harrington (2004). Impact of maternal depression on infant nutritional status and illness: a cohort study. Archives of General Psychiatry 61, 946952.

DR Rubinow (2005). Reproductive steroids in context. Archives of Women's Mental Health 8, 15.

DR Rubinow , MC Hoban , GN Grover , DS Galloway , P Roy-Byrne , R Andersen , GR Merriam (1988). Changes in plasma hormones across the menstrual cycle in patients with menstrually related mood disorder and in control subjects. American Journal of Obstetrics and Gynecology 158, 511.

PJ Schmidt , LK Nieman , MA Danaceau , LF Adams , DR Rubinow (1998). Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. New England Journal of Medicine 338, 209216.

D Sit , H Seltman , KL Wisner (2011). Seasonal effects on depression risk and suicidal symptoms in postpartum women. Depression and Anxiety 28, 400405.

DE Stewart , KM Boydell (1993). Psychologic distress during menopause: associations across the reproductive life cycle. International Journal of Psychiatry in Medicine 23, 157162.

S Terasaka , Y Aita , A Inoue , S Hayashi , M Nishigaki , K Aoyagi , H Sasaki , Y Wada-Kiyama , Y Sakuma , S Akaba , J Tanaka , H Sone , J Yonemoto , M Tanji , R Kiyama (2004). Using a customized DNA microarray for expression profiling of the estrogen-responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals. Environmental Health Perspectives 112, 773781.

IS Yim , LM Glynn , CD Schetter , CJ Hobel , A Chicz-Demet , CA Sandman (2010). Prenatal beta-endorphin as an early predictor of postpartum depressive symptoms in euthymic women. Journal of Affective Disorders 125, 128133.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Type Description Title
UNKNOWN
Supplementary Materials

Mehta Supplementary Material
Table S3

 Unknown (652 KB)
652 KB
UNKNOWN
Supplementary Materials

Mehta Supplementary Material
Figure 1

 Unknown (142 KB)
142 KB
UNKNOWN
Supplementary Materials

Mehta Supplementary Material
Table S4

 Unknown (26 KB)
26 KB
UNKNOWN
Supplementary Materials

Mehta Supplementary Material
Table S1

 Unknown (31 KB)
31 KB
UNKNOWN
Supplementary Materials

Mehta Supplementary Material
Table S2

 Unknown (39 KB)
39 KB
UNKNOWN
Supplementary Materials

Mehta Supplementary Material
Figure 2

 Unknown (108 KB)
108 KB