Elsevier

Psychoneuroendocrinology

Volume 32, Issue 2, February 2007, Pages 133-139
Psychoneuroendocrinology

Immune, health and endocrine characteristics of depressed postpartum mothers

https://doi.org/10.1016/j.psyneuen.2006.11.007Get rights and content

Summary

The purpose of the study was to examine demographic, immune, endocrine, stress and health characteristics of depressed mothers, measured between 4 and 6 weeks postpartum, and compare them to non-depressed mothers. The top decile (N=25) of Profile of Mood States depression scores was used to categorize mothers as depressed and these data were then compared to means of the remaining mothers (N=175) in a study of stress and immunity during the postpartum. Depressed mothers were younger, had smaller birth weight infants, and their babies experienced more illness symptoms at 4–6 weeks postpartum. Depressed mothers were less likely to be breastfeeding and had lower serum prolactin levels. Depressed mothers were more likely to smoke, to have daytime sleepiness, and more symptoms of infection than non-depressed mothers. Depressed mothers also had higher perceived stress, postpartum stress, and negative life event reports.

There was evidence suggesting that depressed mothers had a downregulated hypothalamic–pituitary–adrenocortical (HPA) axis, in that salivary cortisol was lower in depressed mothers. Depressed mothers also had lower serum levels of Interferon-gamma (IFN-γ) and a lower IFN-γ/Interleukin-10 (IL-10) ratio in both sera and in whole blood stimulated cultures, suggesting a depressed Th1/Th2 ratio in depressed mothers. The data supports the possibility that postpartum depression may be associated with a dysregulated HPA axis and possible depressed cellular immunity.

Introduction

Postpartum depression (PPD) is described as a depressed mood, with or without anxiety, sleep disturbances, appetite disturbances, lack of energy, feelings of guilt and/or worthlessness, and decreased concentration. PPD usually occurs within the first 6 months of delivery (Hendrick et al., 1998) and occurs in 10–15% of postpartum woman (O’Hara and Swain, 1996). A woman is considered predisposed to PPD if she has a history of premenstrual syndrome, episodes of depression, life events that are stressful, lack of adequate support, previous PPD, or a family history of depression (O’Hara and Swain, 1996; Wisner et al., 2002). Other causative social factors include a poor marital relationship, primiparity, multiparity, and especially multiparity with short intervals between pregnancies (Gurel and Gurel, 2000). Poverty has been found to double the incidence of PPD (Hobfoll et al., 1995; Ritter et al., 2000).

Many etiologies of PPD have been proposed but it is unlikely that any single hypothesis can explain what appears to be heterogeneous. It is probable that complex interactions between hormones, neurotransmitters, and environmental factors are involved. Current prevailing hypotheses include the following: (1) dietary deficiencies and/or metabolic disorders, (2) alterations in biopterin/neopterin levels, (3) iron-deficiency anemia, (4) thyroid dysfunction and/or thyroid autoantibodies, (5) rapid changes in hormone levels in the postpartum, (6) hormonal changes and alterations in circadian rhythms and (7) hypothalamic–pituitary–adrenocortical (HPA) axis alterations and inflammatory mechanisms. Since we had completed a fairly large study of postpartum stress and immunity that included mood, endocrine and immune measures, we focused our analyses on variables suggested by the last hypothesis.

Studies have generally not found relationships between serum cortisol levels and PPD (Hendrick et al., 1998). However, few studies have measured free cortisol, and plasma levels reflect 90% binding to cortisol binding globulin (CBG). Cortisol is active only in the unbound state, and urinary free cortisol or salivary cortisol are better measures of the active form of cortisol. An early study did not find an association between salivary cortisol and postpartum mood (Harris et al., 1994) measured through pregnancy and until 35 days postpartum. In another study, morning salivary cortisol levels were higher on days 1–5 after birth in women experiencing postpartum blues (Ehlert et al., 1990). However, PPD is a different phenomenon than postpartum blues, which are common and self-limiting, occurring in the early days after birth.

It has been suggested that the hypercortisolism of late pregnancy might cause the development of adrenal suppression in the postpartum after the withdrawal of the extraordinarily high levels of plasma corticotrophin releasing hormone (CRH) produced by the placenta at birth (Magiakou et al., 1996; Kalantaridou et al., 2004). High levels of placental CRH during pregnancy suppress the production of hypothalamic CRH and after birth CRH production and CRH receptors in the hypothalamus may be down-regulated, resulting in decreased ACTH response and cortisol release. Women who develop postpartum blues or PPD may be more than usually suppressed. In susceptible women this decreased CRH response may continue with production of a resultant hypoadrenal state that is further exacerbated by the drop in estradiol after birth (Kammerer et al., 2006). A suppressed HPA axis has been suggested as a factor in the etiology of postpartum affective disorders in general. Such a CRH resistance state is similar to that observed in atypical/seasonal depression, chronic fatigue and fibromyalgia syndromes, and post-Cushing's syndrome therapy as times when patients undergo hypocortisolism.

In support of this theory, a study of 17 euthymic pregnant women, starting at week 20 of gestation, found one who developed depressive symptoms postpartum, and seven who developed the blues (Altemus et al., 1995). The euthymic women had a blunted plasma ACTH response to ovine CRH (oCRH), which returned to non-pregnant, normal levels by the 12th week postpartum. However, the women with the blues or outright depression maintained a much longer blunted plasma ACTH response to oCRH, although there were no appreciable differences in cortisol levels between the euthymic and dysthymic groups. Magiakou et al. (1996) also reported that women with PPD and postpartum dysphoria had a blunted ACTH response to oCRH. They studied the plasma ACTH response to CRH in postpartum women and found that women had a marked blunting of the ACTH response at 3 and 6 weeks postpartum, which became normal by 12 weeks. The lack of ACTH response was greater in those who developed either the blues or depression. Another small study showed that women with PPD had lower serum cortisol levels compared to controls (Parry et al., 2003). Tsigos and Chrousos (2002) suggested that CRH potentiators might be used to treat PPD and atypical depression. On the other hand, in vivo experiments with healthy women do not support blunting of the cortisol response to CRH in the postpartum. Attempting to mimic pregnancy and the puerperium in healthy, medication-free, non-pregnant women, by first injecting supraphysiological doses of estradiol and progesterone, and then precipitously withdrawing these hormones, the investigators then challenged the HPA by injecting oCRH. Cortisol release in response to ovine CRH was enhanced by supraphysiological levels of gonadal steroids (mimicking the pregnancy state) and this response was actually greater in women with a history of PPD (Bloch et al., 2005). This novel approach nevertheless does not fully reproduce the endocrinology of pregnancy or the postpartum. Estradiol has been used to treat PPD and is presumed to reestablish the normal stress response to CRH (Gregoire et al., 1996).

Potentially related to the HPA axis are the immunological changes characteristics of PPD. These studies have generally been done in the very early postpartum, however, and have focused on innate immunity. (Maes et al. (2000) found in a study of 91 pregnant women that serum IL-6, IL-1RA, and leukemia inhibitory factor receptor (LIFR) were significantly higher by the end of pregnancy and in the early postpartum period. There was a positive correlation between IL-6, IL-1RA levels and depressive and anxiety symptoms, “suggesting activation of cells of the macrophage/monocytic lineage in the former” (Maes et al., 2000, p. 133). In an earlier study, Maes et al. (1995) found that increased serum IL-1-RAs levels were positively correlated with major depression.

Maes et al. (2004) studied whether primiparae were more anxious in the early postpartum and more likely than multiparae to develop PPD. Previous work (Maes et al. (2000)) had shown that changes in serum prolyl endopeptidase (PEP) were correlated to increased anxiety and PPD. PEP may play a role in unipolar, bipolar, and major depressive disorders (Maes et al., 1994; Williams et al., 2002). PEP cleaves peptide bonds on the carboxyl side of proline in several active neuropeptides, including arginine vasopressin (AVP), thyrotropin-releasing hormone (TRH), substance P, oxytocin, bradykinin, and neurotensin (Welches et al., 1993). Maes et al. (2004) found that the neuroimmune response in primiparae was different than in multiparae both quantitatively and qualitatively. Primiparae demonstrated (1) higher anxiety levels and (2) changes in the immune response system and PEP. Their findings raise the question of length of time higher levels of PEP and lowered immune response continue in primiparous mothers (or in any mothers with anxiety and depression) since their study measured serum levels only within the first 6 days post delivery. Of relevance to the current research is Maes et al.'s (1994) finding that PEP activity was negatively correlated with post-Dexamethasone Suppression Test (DST) cortisol levels.

Few studies have simultaneously examined both endocrine and immune variables in postpartum women. Yet, there is a large body of research demonstrating relationships between stress hormones, depression and immune function. The general finding is that elevated stress hormones act via specific immune cell receptors to activate macrophages, inhibit Th1 cell activity, and activate the Th2 axis (Vedhara and Irwin, 2005). However, the postpartum is a unique state in terms of the HPA axis, and depression in the postpartum may manifest in a different manner than at other times of life. Since depression is so common in the postpartum, and other research has found relationships between depression, the HPA axis, and immunity, these were the variables of interest in this study.

Section snippets

Method

Data collected in a large study of stress and immunity in postpartum women (Groer et al., 2005) allowed the researchers to do a secondary analysis to examine those women who were significantly depressed, as measured by scores on the Profile of Mood States-Depression (POMS-D), at 4–6 weeks postpartum and compare them to non-depressed women. Demographic, endocrine, immune, stress, mood, and health characteristics of the depressed mothers were compared to non-depressed mothers. Variables chosen

Results

There were 199 mothers, 101 exclusive or nearly exclusive breastfeeders and 98 formula feeders, who completed the study. The mean time of measurement was 5.3 weeks postpartum. Depressed mothers were categorized as those with scores in the highest decile on the POMS-D scale (N=25). Their POMS-D mean score was 32.1 (range 21–47). The mothers with scores below the lowest limit of the top decile (N=169) had a mean POMS-D scores of 5.7 (range 0–20). The top decile was chosen as a group representing

Discussion

The mothers with the highest scores on the POMS-D were demographically like mothers in other studies. The incidence of depression in this sample was approximately 10%, when using the POMS-D as the measure of depression but these mothers were measured only at one time point, so the true incidence across the postpartum year is unknown. While the POMS is highly reliable and highly correlated with other depression scales in many populations, it is not one of the gold standards for measuring

Acknowledgments

This work has been supported by NIH NR01–5000.

References (42)

  • P. Owens et al.

    Postnatal disappearance of the pregnancy-associated reduced sensitivity of plasma cortisol to feedback inhibition

    Life Sci.

    (1987)
  • C. Tsigos et al.

    Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress

    J. Psychosom. Res.

    (2002)
  • W. Welches et al.

    A comparison of the properties and enzymatic activities of three angiotensin processing enzymes: angiotensin converting enzyme, prolyl endopeptidase and neutral endopeptidase 24.11

    Life Sci.

    (1993)
  • M. Abou-Saleh et al.

    Hormonal aspects of postpartum depression

    Psychoneuroendocrinology

    (1998)
  • M. Altemus et al.

    Suppression of hypothalamic pituitary–adrenal axis responses to stress in lactating women

    J. Clin. Endocrinol. Metab.

    (1995)
  • S. Ashman et al.

    Stress hormone levels of children of depressed mothers

    Dev. Psychopathol.

    (2002)
  • S. Bass et al.

    Relationships of breast and bottle feeding practices with infant health in an urban poor population

    J. Perinat. Neonatal Nurs.

    (1997)
  • M. Bloch et al.

    Cortisol response to ovine corticotrophin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression

    J. Clin. Endocrinol. Metab.

    (2005)
  • S. Cohen et al.

    A global measure of perceived stress

    J. Health Soc. Behav.

    (1983)
  • I. Elenkov et al.

    IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: implications for autoimmune disease activity during these times

    J. Clin. Endocrinol. Metab.

    (2001)
  • M. Groer et al.

    Relationships between self-reported symptoms of infection, menstrual-cycle-related distress, and cycle phase

    Behav. Med.

    (1993)
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