Research Letters

Sublingual oestrogen treatment of postnatal depression

Clinical research has demonstrated a significant sex difference in the occurrence of depressive disorders. Beginning at pubertal onset, women report a higher incidence of depression than men. Women are also vulnerable to the development of depressive disorders such as premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression. These disorders are associated with reproductive stages involving changes in gonadal hormone levels. Specifically, female depression and female affective behaviors are influenced by estradiol levels. This review argues two major mechanisms by which estrogens influence depression and depressive-like behavior: through interactions with neurotrophic factors and through an influence on the serotonergic system. In particular, estradiol increases brain derived neurotrophic factor (BDNF) levels within the brain, and alters serotonergic expression in a receptor subtype-specific manner. We will take a regional approach, examining these effects of estrogens in the major brain areas implicated in depression. Finally, we will discuss the gaps in our current knowledge of the effects of estrogens on female depression, and the potential utility for estrogen receptor modulators in treatment for this disorder.

In women, breastfeeding generally results in reductions in anxiety and increased positive mood. However, approximately 10–15% of women experience depressed mood and increased anxiety during the first year postpartum. Recent research has demonstrated that offspring-exposure is important for the reduction in behaviours related to depression and anxiety in the mother. It remains to be determined whether these effects are due to factors related to pregnancy and/or pup-exposure, are associated with the degree of maternal behaviour by the mother towards offspring, or persist after weaning. To address these questions the present study used four groups of female rats; primiparous, nulliparous, primip-no-pups (primiparous females with pups permanently removed), and sensitized females. Depressive- and anxiety-like behaviours were assessed 1 week after weaning/pup-exposure (4 weeks after birth for primip-no-pups animals) using the forced swim test for measures of depressive-like behaviour, and the open field test and elevated plus maze for measure of anxiety-like behaviour. Results demonstrate that primiparous females without pup-exposure have increased depressive-like, but not anxiety-like, behaviour compared to primiparous and sensitized females. In addition, kyphotic nursing by primiparous mothers was negatively related to behavioural measures of depression and anxiety. From this work it is clear that pup-exposure is important for reductions in depressive-like behaviour in parturient females. Further research is needed to determine the extent of these changes and the neural and hormonal correlates of these events.

There is now compelling evidence that gonadal steroid hormones, through cellular and molecular mechanisms of action in the brain, influence behavioral and physiological processes that go beyond their traditional role in the regulation of hypothalamic activity and reproduction. These actions begin during gestation and may produce organizational, long-lasting, structural changes leading to sexual dimorphisms. This chapter focuses on the effects of gonadal steroid hormones on reward processing and decision-making, which critically depend on dopaminergic neurotransmission. It reviews evidence from animal and human studies that indicate the important roles played by variations of gonadal steroid hormones on a number of cerebral inter-individual differences (e.g., between men and women, between hypogonadal patients and healthy subjects) and intra-individual differences (e.g., differences across phases of the menstrual cycle or at different stages of the lifespan, such as menopause or andropause). Taken together, these studies help to understand the impact of gonadal steroids on vulnerability to drug abuse, neuropsychiatric diseases with differential expression across males and females, and hormonally mediated mood disorders.

Previous reports suggest that massive hormonal changes that accompany the peripartum period may trigger perinatal depression. We investigated the relationship between magnitude of change and total level of estrogen and progesterone and grade of peripartal depression and depressive symptoms. One hundred and ninety two women were assessed in the 38th week of pregnancy (SDS scores), peripartum period (DSM-III-R diagnosis (n = 105); SDS scores) and 6 months postpartum (EPDS; n = 89) regarding diagnosis of depression, self-ratings of depressive symptoms and levels of estrogen and progesterone. The comparison of three diagnostic groups (lifetime major depressive disorder MDD (N = 7), MDD at birth (N = 12), healthy controls (N = 70) showed that there were no differences in the magnitude of decline of estrogen and progesterone from day 1 to day 3 after birth . With respect to total levels of estrogen and progesterone, estrogen on day 3 was significantly higher [F(2, 92) = 6.6, p < 0.05] in women with current MDD than in those with lifetime MDD or normal controls. Depression scores were significantly higher at the end of pregnancy (12.6% self-identified as depressed) than in postpartum period (5.8% day 3 p < .0004; 9.2% day 5 p < .008), whereas 13.3% of women received a DSM-III –R diagnosis for MDD 5 days postpartum.

The results were in contrast to the current hypotheses of estrogen withdrawal or hypogonadal levels as an etiological factor for peripartum depression. But a limitation of the actual study is the low number of subjects with depression; therefore the current non-significant findings should be interpreted with great caution.

to capture the missing voices of mothers who are suffering postnatal depression.

qualitative methodology using in-depth interviews.

Melbourne, Victoria, Australia.

10 women who had been clinically diagnosed and admitted to a large hospital mother and baby unit in Australia.

stigma is frequently attached to women who are unhappy after the birth of their child, because they are not coping with the demands of motherhood or do not instantly bond with, and love, their baby. As a result, postnatal depression can be a terrifying and isolating experience for women. It is also a complex illness with varying degrees, reasons for onset and medical treatments.

in this study, we have captured the emotions and feelings of women first hand, allowing us and health-care practitioners who are treating women to truly understand this debilitating illness. It is hoped that, in making the wider community aware of depression after childbirth, fewer women will suffer in silence.

The effect of hormone withdrawal following hormone-simulated “pregnancy” on “depressive-like behavior” in the Forced Swim Test (FST) was investigated in female Long-Evans rats. Females were randomly assigned to “pregnant”, “pregnant”+estradiol benzoate (EB), and control groups. Both the “pregnant” and “pregnant”+EB groups received daily injections of the hormones estradiol and progesterone to simulate the 23-day gestational period in the rat. However, the “pregnant”+EB group continued to receive daily estradiol injections after “pregnancy”. All groups were tested 48 h after the last injection of the pregnancy period in the FST and subsequently in the Open Field Test (OFT). Results revealed that the “pregnant” rats exhibited significantly increased immobility and decreased struggling and swimming behaviors as compared to the “pregnant”+EB and control groups. These findings could not be explained by an overall depression in general locomotor activity among “pregnant” rats, as the “pregnant” rats made more area crossings in the OFT. Thus “pregnant” rats exhibited behaviors consistent with “depressive-like” symptoms “post-partum” (after their hormone regime was discontinued). Continual treatment with high levels of estradiol in the “pregnant”+EB group, however, reversed the exhibition of these behaviors. These results imply that withdrawal from chronic high levels of pregnancy-associated hormones (estradiol and progesterone) can produce depressed symptomology in rodents, which can be prevented by prolonging exposure to high levels of estradiol through the post-partum period. These findings are the first demonstration of “depressive-like” symptoms in a rodent model of post-partum pregnancy and the ability of high levels of estradiol to attenuate these “depressive-like” symptoms.