Elsevier

Journal of Affective Disorders

Volume 198, 1 July 2016, Pages 108-121
Journal of Affective Disorders

Review article
Thyroid peroxidase autoantibodies and perinatal depression risk: A systematic review

https://doi.org/10.1016/j.jad.2016.03.021Get rights and content

Highlights

  • 11 articles were eligible for qualitative synthesis.

  • High levels of TPO-AB during pregnancy increase risk for antenatal depression.

  • High levels of TPO-AB during pregnancy increase risk for postnatal depression.

  • Postpartum TPO-AB and concurrent depression were weakly associated.

Abstract

Background

While thyroid autoantibodies have been linked to depression in general population samples, it is unclear if the immunological milieu of pregnancy alters this association. As a result, we systematically reviewed the literature to determine if abnormal levels of autoantibodies that target thyroperoxidase (TPO-AB) during the perinatal period are associated with an increased risk of antenatal and postnatal depression.

Methods

MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched through February 2016. Primary studies that examined TPO-AB titers during pregnancy or the postpartum period, and antenatal or postnatal depression were eligible. The quality of each study was assessed using the Newcastle-Ottawa Scale.

Results

Among the eleven articles selected for synthesis, three of these examined associations between TPO-AB and depression both during pregnancy and in the postpartum period. Three of five studies reported statistically significant associations between elevated TPO-AB titers (TPO-AB+) and concurrent depression at 12–25 weeks gestation. Four of five studies found significant associations between TPO-AB+ status at 12–25 weeks gestation and depression in the postpartum period. Two of four studies found links between postpartum TPO-AB and depression concurrently in the puerperium.

Limitations

Lack of adjustment for confounding variables limits causal inference and conclusions about the predictive power of TPO-AB.

Conclusions

Studies suggest that TPO-AB+ in early to mid-pregnancy is associated with concurrent depression and may be predictive of depression in the postpartum period. Future studies with improved methodology are required to better understand the full pathophysiological implications and predictive utility of TPO-AB in perinatal depression.

Introduction

Depression during the perinatal period is associated with an increased risk of adverse outcomes for both women and their children. Depression during pregnancy (i.e., antenatal depression) has been linked to elevated rates of obstetrical complications (Grote et al., 2010), as well as depression in the postpartum period (O’hara and Swain, 1996). Postnatal depression is associated with impaired mother-infant bonding (Moehler et al., 2006, O’Higgins et al., 2013) and increased levels of emotional and cognitive problems in offspring during both childhood (Beck, 1998) and adolescence (Hay et al., 2008, Korhonen et al., 2014, Murray et al., 2010, Verbeek et al., 2012).

Research suggests that the etiology of perinatal depression involves a combination of social (Beck, 2001, Lancaster et al., 2010), psychological (Bunevicius et al., 2009a, Leigh and Milgrom, 2008, O’hara and Swain, 1996, Zeng et al., 2015), and biological factors (Leung and Kaplan, 2009, Meltzer-Brody, 2011, Serati et al., 2016, Skalkidou et al., 2012). Indeed, dysregulation of various endocrine systems have been implicated in the pathophysiology of both antenatal and postnatal depression (Meltzer-Brody, 2011, Serati et al., 2016, Skalkidou et al., 2012). Multiple studies examining associations between thyroid hormones (e.g., thyroxine, thyrotropin, and triiodothyronine) and depression during the perinatal period have been suggestive of a link (Abou-Saleh et al., 1998, Ijuin et al., 1998, Lambrinoudaki et al., 2010, Pedersen et al., 2007, Pedersen et al., 2016, Saleh et al., 2012, Sylvén et al., 2013), though a consensus does not exist as to whether clinical syndromes of thyroid dysfunction (e.g., hyper- and/or hypothyroidism) are linked to depression in the perinatal period (Basraon and Costantine, 2011, Lazarus, 1997, Lucas et al., 2001, Pop et al., 1991, Walfish et al., 1992).

During pregnancy, the maternal immune system undergoes many changes to accommodate for the development of the fetus (Zenclussen, 2013) and attempts to return to its pre-pregnancy state in the postpartum period. These changes include alterations in the production of autoantibodies that target thyroid antigens such as thyroid peroxidase (TPO-AB)1 (Glinoer et al., 1994, Stagnaro-Green et al., 1992). TPO-AB, previously referred to as microsomal antibody (Portmann et al., 1985, Ruf et al., 1987), is the most common type of thyroid autoantibody found in euthyroid individuals (Hollowell et al., 2002) and is associated with various forms of thyroid dysfunction (Hollowell et al., 2002, Vanderpump et al., 1995). Though not yet fully substantiated, multiple studies have suggested that an association may exist between thyroid autoantibodies and depression in general population samples (Carta et al., 2004, Degner et al., 2015, Pop et al., 1998, van de Ven et al., 2012). However, it is not yet clear if similar associations exist for women in the perinatal period (e.g., McCoy et al., 2008, Harris et al., 1989).

Since an understanding of the links between TPO-AB and depression in the perinatal period not only has important pathophysiological implications, but may also have significant clinical utility, we set out to systematically review studies examining associations between abnormal TPO-AB titers in the perinatal period and depression during pregnancy and the puerperium.

Section snippets

Search strategies for systematic review

We searched MEDLINE, EMBASE, PsycINFO, and CINAHL from their respective inceptions through February 13th, 2016 for studies that examined associations between thyroid indices during pregnancy or the first year of postpartum and antenatal or postnatal depression. The search strategy employed for MEDLINE utilized the following terms: (exp depressive disorder/ or exp depression, postpartum/ or exp depressive disorder, major/ or exp depression/ or exp puerperal disorders/) and (exp obstetrics/ or

Results

Our initial searches yielded 1026, 1284, 38, and 54 studies in MEDLINE, EMBASE, PsycINFO, and CINAHL, respectively (Fig.1). Forty-six full text articles were examined as they were thought to contain data that could address our objective (associations between TPO-AB during pregnancy or the puerperium and antenatal or postnatal depression). Thirty-three failed to contain relevant data and thirteen articles were selected for review. However, two of the thirteen were later excluded because both

Discussion

In this systematic review of studies examining associations between abnormal titers of TPO-AB during the perinatal period and antenatal and postnatal depression, we found that three of five studies reported significant associations between TPO-AB+ and concurrent depression at 12–25 weeks of gestation (Groer and Vaughan, 2013, Kuijpens et al., 2001, Pop et al., 2006). Four of five studies also found significant associations between TPO-AB+ at 12–25 weeks of gestation and depression in the

Conclusions

In summary, the studies comprising this systematic review suggest that associations may exist between TPO-AB+ status during early to mid-gestation and perinatal depression. However, more research is required to clarify the predictive value and pathophysiological implications of these associations. Future studies that adjust for confounding variables, and that examine TPO-AB levels at different time points during pregnancy and the postpartum period, and that define it as a continuous variable

References (71)

  • C. Pedersen et al.

    Late pregnancy thyroid-binding globulin predicts perinatal depression

    Psychoneuroendocrinology

    (2016)
  • M.F. Prummel et al.

    Thyroid peroxidase autoantibodies in euthyroid subjects

    Best. Pract. Res. Clin. Endocrinol. Metab.

    (2005)
  • M. Serati et al.

    Perinatal major depression biomarkers: a systematic review

    J. Affect Disord.

    (2016)
  • S.M. Sylvén et al.

    Thyroid function tests at delivery and risk for postpartum depressive symptoms

    Psychoneuroendocrinology

    (2013)
  • T. Verbeek et al.

    Postpartum depression predicts offspring mental health problems in adolescence independently of parental lifetime psychopathology

    J. Affect. Disord.

    (2012)
  • T.G. Wegmann et al.

    Bidirectional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a TH2 phenomenon?

    Immunol. Today

    (1993)
  • Y. Zeng et al.

    Prevalence and predictors of antenatal depressive symptoms among Chinese women in their third trimester: a cross-sectional survey

    BMC Psychiatry

    (2015)
  • M.T. Abou-Saleh et al.

    Hormonal aspects of postpartum depression

    Psychoneuroendocrinology

    (1998)
  • R. Azar et al.

    Mild depressive symptoms are associated with elevated C-reactive protein and proinflammatory cytokine levels during early to midgestation: a prospective pilot study

    J. Women's Heal

    (2012)
  • S. Basraon et al.

    Mood disorders in pregnant women with thyroid dysfunction

    Clin. Obstet. Gynecol.

    (2011)
  • C.T. Beck

    Predictors of postpartum depression: an update

    Nurs. Res.

    (2001)
  • M.E. Benros et al.

    Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study

    JAMA Psychiatry

    (2013)
  • R. Bunevicius et al.

    Psychosocial risk factors for depression during pregnancy

    Acta Obstet. Gynecol. Scand.

    (2009)
  • R. Bunevicius et al.

    Depressive disorder and thyroid axis functioning during pregnancy

    World J. Biol. Psychiatry

    (2009)
  • M.G. Carta et al.

    The link between thyroid autoimmunity (Antithyroid peroxidase autoantibodies) with anxiety and mood disorders in the community: a field of interest for public health in the future

    BMC Psychiatry

    (2004)
  • J.L. Cox et al.

    Detection of Postnatal depression. Development of the 10-item Edinburgh Postnatal depression scale

    Br. J. Psychiatry

    (1987)
  • D. Degner et al.

    Association between autoimmune thyroiditis and depressive disorder in psychiatric outpatients

    Eur. Arch. Psychiatry Clin. Neurosci.

    (2015)
  • S.L. Farr et al.

    Mental health and access to services among US women of reproductive age

    Am. J. Obstet. Gynecol.

    (2010)
  • D. Glinoer et al.

    Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders

    J. Clin. Endocrinol. Metab.

    (1994)
  • M.W. Groer et al.

    Positive thyroid peroxidase antibody titer is associated with dysphoric moods during pregnancy and Postpartum

    J. Obstet. Gynecol. Neonatal Nurs.

    (2013)
  • N.K. Grote et al.

    A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction

    Arch. Gen. Psychiatry

    (2010)
  • S. Haeri et al.

    Do pregnant women with depression have a pro-inflammatory profile?

    J. Obstet. Gynaecol. Res.

    (2013)
  • M. Hamilton

    A rating scale for depression

    J. Neurol. Neurosurg. Psychiatry

    (1960)
  • B. Harris et al.

    Association between postpartum thyroid dysfunction and thyroid antibodies and depression

    BMJ

    (1992)
  • D.F. Hay et al.

    Antepartum and postpartum exposure to maternal depression: different effects on different adolescent outcomes

    J. Child. Psychol. Psychiatry Allied Discip.

    (2008)
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