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Can hormones in breastfeedingprotect against postnatal depression?

Postnatal depression (PND) is a devastating condition affecting the mental health of an increasing number of women following

birth (Royal College of Midwives (RCM), 2007). Prevalence rates vary between studies but an average prevalence of 13% can be suggested (Dennis, 2005; National Institute for Health and Clinical Excellence (NICE), 2006; Horowitz et al, 2009). Symptoms include tearfulness, persistent low mood and fatigue, lack of drive and insomnia with most cases starting in the first 3 months post-partum (Dennis, 2005).

The evidence for the benefits of breastfeeding in helping to reduce PND has previously been considered (Donaldson-Myles, 2011), and found the evidence to be inconclusive, with study results confounded by unclear definitions of breast-feeding. However, it is generally accepted that formula feeding mothers experience more depressive symptoms than their breastfeeding counterparts (Dennis and McQueen, 2009). The question is whether this is because depressed mothers are less likely to succeed in their attempts to breastfeed, thereby compounding depressive mood, or whether breastfeeding in itself confers some protection against depression? This article

explores the possible psycho-protective role of the hormones specifically related to lactation and reviews the evidence which helps explain why breastfeeding mothers appear to be at a lower risk of PND.

Do hormonal changes cause PND?During pregnancy and the puerperium major hormonal changes take place in the body as a result of alterations to the hypothalamic-pituitary-adrenal (HPA) axis. These include the placenta producing the hormones progesterone and oestrogen which maintain and nurture the preg-nant state. Levels of these hormones fall sharply at birth, reaching pre-pregnancy levels at around the fifth postpartum day (Dalton, 1989; Hendrick et al, 1998).

The possibility of a biological link between the hormonal environment of the puerperium and depression has been suggested since the time of Hippocrates (Hanley, 2009); however, many authors explored this relationship by looking at how hormonal changes may cause PND. It is known, for example, that a steep fall in proges-terone after delivery has an association with the ‘baby blues’ (Harris et al, 1994; Glangeaud-Freudenthal et al, 1999) Recent research, however, suggests that certain endocrine changes present in breastfeeding women may actually help prevent PND (Abou-Saleh et al, 1998; Klier et al, 2007).

What is the role of prolactin?It is known that the secretion of the lactogenic hormone prolactin increases during pregnancy, rising steadily until delivery. Production is then further stimulated by the baby suckling at the breast. It is produced by the adenohypophysis (the anterior lobe of the pituitary gland), situated at the base of the skull (Box 1). It is the main stimulant for milk production. Its secretion is influenced by biochemical circadian rhythms being produced in larger quantities when the woman is asleep. Following birth, prolactin levels remain high if the woman is breastfeeding on demand and this stimulates milk production further. The raised prolactin inhibits the production of oestrogen, progesterone and follicle-stimulating hormone

AbstractThe benefits of breastfeeding are widely accepted; however, one of the likely advantages of breastfeeding is often overlooked: breastfeeding may help protect against postnatal depression. An earlier article (Donaldson-Myles, 2011) reviewed the evidence of the beneficial effects of breastfeeding against postnatal depression. This article now examines the hormonal changes engendered by human suckling and lactation which appear to reduce the incidence of depression. It explores the role of stress and inflammation in depression together with the attenuating effects of the hormones of lactation. Prolactin and oxytocin are shown to have an inhibitory influence on the hypothalamic-pituitary-adrenal axis which is activated at times of stress. In addition, evidence that oxytocin has a central calming effect on the brain is discussed. An understanding of the moderating effects of the lactational hormones on postnatal depression could assist midwives in encouraging vulnerable women to breastfeed and help combat this devastating condition. Using this evidence-based information, midwives can utilize their valuable and limited time to encourage and support breastfeeding in women who are prone to depression to help improve their mental wellbeing.

Fiona Donaldson-MylesSupervisor of Midwives,The Soldiers, Sailors, Airmen and Families Association - Forces Help (SSAFA), The Princess Mary’s Hospital, RAF Akrotiri, BFPO 57

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Can hormones in breastfeedingprotect against postnatal depression?

in a negative feedback mechanism and ovula-tion is initially suppressed. In this way exclusively breastfeeding women differ from formula feeding women in that they have high serum prolactin levels and are generally anovulatory. In non-breast-feeding women prolactin levels return to normal within 3–4 weeks post-delivery (Alder et al, 1986; Hendrick et al, 1998).

Various studies have pointed to the possibility that raised prolactin levels protect against PND. Abou-Saleh et al (1998) undertook an investiga-tion into 70 postpartum women in Dubai who were assessed at 7 days using the Edinburgh Postnatal Depression Score (EPDS). Blood samples for a range of hormones were taken twice on the day of the mental health assessment.

Unfortunately, only 34 postpartum partici-pants agreed to the venepuncture, limiting the study’s strength, but it did involve two compar-ison groups: 23 women still pregnant and 38 non-pregnant women. The findings showed that postpartum women had significantly higher levels of prolactin than the controls and that those who breastfed had significantly higher levels than non-breastfeeders with significantly lower EPDS scores.

When a statistical analysis of all the variables was made, decreased prolactin was found to be one of the accurate predictors of depression, as was non-breastfeeding, increased progesterone and increased maternal age. This was a very small study but the findings were supported by Harris et al (1989) whose extensive research into the role of hormones in PND found that a low plasma prolactin is associated with depression irrespec-tive of the method of feeding. Asher et al (1995) found that the only hormonal change consist-ently associated with a raised EPDS score was low prolactin.

Maureen Groër (2005), in her research into 138 mothers’ feeding method and hormone status during the first 4 weeks after delivery, found the most significant finding in relation to prolactin was that the low levels found in formula feeding mothers correlated with an increase in stress and low mood. Groër et al (2005) came to the same conclusion when they assessed endocrine and immune relationships with postpartum fatigue. They found that the higher levels of prolactin in breastfeeding women seemed to buffer the effects of stress. Groër describes how stress in the post-partum period activates the HPA axis, normally leading to increased release of cortisol, the stress hormone, but prolactin and oxytocin inhibit this response. She has called this protective mech-anism the ‘lactational stress resistance model’ (Groër, 2005: 108).

What is the role of oxytocin?Oxytocin is a neuro-hormone that plays an impor-tant part in the physiology of lactation. Oxytocin found in the peripheral circulation is synthesized in the hypothalamus and stored in the poste-rior pituitary gland before being released into the bloodstream (Box 2). Plasma levels increase during pregnancy and rise further at birth. Oxytocin has long been known to have an effect on uterine contractibility and milk ejection from the breast and is released into the blood during breastfeeding, resulting in much higher levels of oxytocin in breastfeeding women than in women who are formula feeding. It is widely thought that oxytocin moderates stress responses by reducing the secretion of adrenocorticotropic hormone (ACTH) and cortisol (Windle et al, 1997; Boutet et al, 2006; Jolley et al, 2007). In addition to being released into the bloodstream under the influence of the hypothalamus, oxytocin is also produced by pariocellular neurones in the brain and can be released centrally where it acts as a neuro-peptide hormone—a neuro-signalling molecule—acting on the central nervous system (Cyranowski et al, 2008). Special pathways for the passage of oxytocin exist in the brain and there are significant levels of oxytocin in cerebrospinal fluid (Argiolas and Gessa, 1991). This suggests that oxytocin produc-tion and release is a complex biochemical process that cannot be measured by plasma levels alone.

Box 1. Prolactin l Prolactin, the lactional hormone, is produced in the anterior lobe of the pituitary gland

l Production is circadian and increases during sleep l Levels rise throughout pregnancy and are highest in breastfeeding women l Low prolactin is associated with depression l High levels of prolactin seem to buffer stress responses by opposing the effect of cortisol

Box 2. Oxytocin l Oxytocin is a neuro-hormone which is present in the peripheral circulation, the cerebrospinal fluid and the brain

l It has a short half-life and its release is pulsatile, making accurate measurement difficult

l Levels rise in pregnancy and are high in breastfeeding women as it is the hormone of uterine contractibility and milk ejection

l It is strongly associated with successful mother-baby bonding and pair bonding in mammals

l In humans oxytocin has been shown to reduce stress, have a calming effect and improve mood by moderating the effects of adrenocortico-tropic hormone (ACTH) and cortisol

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Since the early 1960s oxytocin has been thought to play a complex and multi-role function in maternal behaviour and stress. It is strongly impli-cated in mother-baby bonding and pair-bonding success in mammals (Turner et al, 2002). Animal research has shown that oxytocin production increases when female mammals are under stress and that when this happens the females exhibit more serene behaviour (Windle et al, 1997). In mouse experiments, Arletti and Bertolini (1987) described oxytocin working as an ‘anti-depressant’ and demonstrated that reduced oxytocin levels led to poor maternal behaviour and increased anxiety. Grippo et al (2007) found that when they subjected female prairie voles to social isolation, the voles displayed characteristics of depression such as reduced self-interest, but when their levels of plasma oxytocin rose, there were positive changes in behaviour such as increased grooming, feeding and care for their young. They postulated that these raised oxytocin levels were a biochemical response to stress and had a soothing effect which promoted social engagement. Several studies have also shown that oxytocin has an amnesic effect on animals (Argiolas and Gessa, 1991; de Wied et al, 1993) which could possibly be useful in helping to forget stressful experiences or pain. The evidence from these animal studies strongly points to oxytocin having an inhibiting role on cortisol.

Extrapolation from animal studies to humans should of course be treated with caution. It is known that oxytocin is released into the human circulation in a pulsatile fashion, making assess-ment through blood sampling at timed intervals potentially inaccurate. In addition, human oxytocin is thought to have a short half-life, making assessment even more difficult (Amico et al, 1987; Boutet at al, 2006). Animals allow unrestricted access to the breast whereas humans may feed in a set pattern or mix mechanical expression with breast suckling and we do not know how different feeding behaviour might affect oxytocin produc-tion. Thus these factors make the application of animal research to the human situation complex. However, the potential for further research into the relationship between oxytocin and enhanced maternal mood is tremendous and begs the ques-tion ‘do women who have high oxytocin levels benefit from a natural anxiolytic?’

Turner et al (2002) looked at the effect strong emotions such as aggression and anxiety might have on plasma oxytocin levels in women by inducing these feelings in the research setting and measuring serum concentrations. They found that those participants who showed a rise in oxytocin exhibited less feelings of anxiety but overall the findings were not statistically significant. The authors acknowledged that problems with stud-ying oxytocin release includes its episodic and pulsatile secretion, its tendency to be affected by circadian rhythms and the inaccessibility of meas-uring oxytocin in cerebrospinal fluid.

However, Uvnäs-Mobcrg et al (1990) found that oxytocin levels in lactating women did show a negative correlation with the emotions of aggres-sion, guilt and suspicion and that women felt calm and less anxious during breastfeeding when their oxytocin levels were highest. Boutet et al (2006) found that the first hour of breastfeeding, when plasma oxytocin concentration is greatest, seemed to protect women from psychological distress. Mezzacappa and Katlin (2002) also investigated this link by studying the immediate effect of breast-feeding or bottle feeding on the same mother. Women who were both breast and formula feeding had their feelings and reactions assessed before and after feeding their baby. Participants were blind to which method of feeding they were about to give the baby and were asked to score their mood on a self-report scale before and after the feed. Physiological responses were also measured. The results showed that mood became signifi-cantly less positive from pre- to post-feed when the mother gave a formula feed compared to when she breast fed. The mood then became significantly

Prolactin and oxytocin have been shown to have an inhibitory influence on the hypothalamic- pituitary-adrenal axis activated at times of stress.

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less negative after breastfeeding sessions. This finding indicated that, in the same mother, the act of breastfeeding by itself decreased negative mood compared to giving a feed by bottle. Albeit a small study, this research was unique in this field in that by using the same mothers there was no difference in the characteristics of the two groups. There was something about the breastfeeding that appeared to reduce feelings of stress despite all other param-eters remaining the same.

The researchers speculated that the surge of oxytocin at suckling might be responsible for this effect, acting as an ‘endogenous anti-depressant’ and went on to suggest that, in line with research on oxytocin improving mother-infant bonding, the positive feeling achieved following suckling may become a self-fulfilling prophecy enhancing positive perceptions of the baby. However, alter-nate explanations for these differences should not be discounted.

Breastfeeding, depression and inflammation Inflammation is a process which occurs in the body in response to both physical and psycho-logical stress. In response to insults of stress the sympathetic nervous system releases catecho-lamines such as dopamine, epinephrine, serotonin and angiotensin and the HPA axis is stimulated to produce ACTH and cortisol (Raison et al, 2006) (Box 3).

The psycho-neuro-immunological response to the release of these stress hormones is an increase in the production of pro-inflammatory cytokines—messenger molecules which stimu-late inflammation and are involved in wound healing, allergic responses, and auto-immune diseases (Groër and Davis, 2006; Kendall-Tackett, 2007). Cytokines require a receptor T-cell to cause a response. It is thought that the release of cortisol and cytokines in particular initiate an acute phase reaction (APR) which results in an increased production of T-cells, mast cells, plate-lets, lymphocytes, APR proteins, such as C-reactive protein, and lipids. The result is that the body is in a neuro-inflammatory state with an altered endo-crine and immunological profile. When cytokines are within normal response levels they are protec-tive against infection and strengthen the immune system. However, if the level becomes abnormally high, as in cases of severe or chronic inflamma-tion, they become dysfunctional and ineffective and their presence contributes to the effects of the other abnormal endocrine secretions resulting in alterations in sleep patterns, appetite and mood (Raison et al, 2006).

In 2003 a comprehensive literature review showed that over 150 studies demonstrated a link between depression and inflammatory responses in the body (Padgett and Glaser, 2003). In 2007, in her review of the literature on inflammation and maternal mental health, Kendall-Tackett argued that as inflammation is a key factor in depression, postpartum women are at increased risk because their inflammation levels are natu-rally elevated due to the immune system already being altered due to pregnancy, with postpartum women experiencing some of the known pro-inflammatory stimulators such as fatigue, pain and trauma (Kendall-Hackett, 2007).

Kendall-Tackett (2007) advocated exclusive breastfeeding as a positive natural intervention to reduce the risk of PND by attenuating stress responses and reducing the inf lammatory response of the body. In her assessment of the impact of pain as a trigger for inflammation she highlights how common nipple pain is in breastfeeding and stresses that breastfeeding difficulties should be dealt with promptly to ‘halt the cascade of stress hormones and pro-inflam-matory cytokines, decreasing their risk [sic] for depression’ (Kendall-Tackett, 2007: 8). Maureen Groër (2005) has also concluded that stress, inflammation and fatigue reduce immunity to infection in postpartum women and that breast-feeding seems to moderate the effect. She found that immunity was decreased and susceptibility to infection was increased in depressed bottle feeding women but not in depressed breast-feeding women.

‘Recent and robust studies have largely supported the proposition that breastfeeding can help protect women from the effects of stress.’

Box 3. Depression and chronic inflammation l Depression can lead to neuro-inflammatory changes which reduce immunity

l Inflammatory responses are partly provoked by adrenocorticotropic hormone (ACTH) and cortisol released from the hypothalamic- pituitary-adrenal (HPA) axis

l The hormones of breastfeeding counter the effects ACTH and cortisol l Breastfeeding women may experience less inflammation and be less susceptible to infection

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Groër et al (2004) also established that when a lactating mother was under psychological stress there was an increase in immunoglobulin A (IgA) secreted in breast milk. Only exclusively breast-feeding women were included in this study. The authors assessed women’s mood state and infec-tion symptoms at 4–6 weeks post-delivery. Samples of hindmilk, foremilk and blood were collected. Raised breast milk IgA was positively associated with raised maternal serum cortisol suggesting that stress in the postpartum woman stimulates the HPA axis and this is turn affects the content of the milk. The finding that the content of human milk can alter in response to maternal stress and that the alteration is an increased produc-tion of immunoglobulins, improving protection from infection for the child, is a profound finding. This is strong evidence to support the theory that a two-way psycho-neuro-hormonal pathway concerning mood and lactation exists; mood being capable of influencing serum and breast milk content and the act of breastfeeding influencing secretions, in turn affecting mood.

ConclusionsThis review explored the hormones related to breastfeeding and the positive influence they have on maternal mood. The stress-related inflam-matory process and its effect on mood was also described with particular reference to the post-natal state and breastfeeding

The likely psycho-protective effects of breast-feeding are often overlooked or put down to folklore, but recent and robust studies have largely supported the proposition that breast-feeding can help protect women from the effects of stress. Research on the hormones of lactation has established that their role, although not fully

understood in humans, is fundamental to the link between breastfeeding and PND. Prolactin, oestrogen and progesterone are easier to study than oxytocin. Despite the importance of the rela-tionship between oxytocin and maternal mental health, research into the full role of oxytocin is not likely to expand in the near future due to the difficulty in quantifying such an elusive and shifting neuro-hormone and to the ethical issues involved in studying vulnerable groups such as pregnant and postpartum women.

This review shows there is credible scientific evidence to support the proposition that breast-feeding helps protect against PND. It is important that midwives understand the physiology and neuro-endocrinology of breastfeeding in order to give well-informed and effective advice on the links between breastfeeding and improved maternal mental health. BJM

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l These hormones may also increase the immunoglobulin levels in breast milk helping to protect the baby against infection

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