New Research on Postpartum Depression:
The Central Role of Inflammation and How Breastfeeding and Anti-Inflammatory Treatments Protect Maternal Mental Health
Kathleen Kendall-Tackett, PhD, IBCLC
From: LEAVEN, Vol. 43 No. 3, July-August-September 2007, pp. 50-53
In the August-September 2005 issue of LEAVEN, I summarized emerging research trends on postpartum depression (see "New Studies in Postpartum Depression," pages 75-79). Two years have passed since that last article, and what researchers have discovered in the interim has important implications for Leaders and lactation consultants. By understanding the processes that increase mothers' risk of depression, we can be more effective in our work with them. Central to our new understanding of depression is our expanded view of the role of stress.
The Stress Response: How Our Bodies Respond to Perceived Threat
When we are faced with threat, our bodies have a number of mechanisms designed to protect our lives. Three interrelated systems respond: catecholamine, hypothalamic-pituitary-adrenal (HPA) axis, and the immune system. The catecholamine system (the fight-or-flight response) releases three neurotransmitters (chemical substances that transmit nerve impulses): norepinephrine, epinephrine, and dopamine. The HPA axis also releases several hormones including the stress hormone cortisol. In recent years, researchers have discovered that the immune system also responds to threat by releasing molecules that increase inflammation. These molecules are known as proinflammatory cytokines and they have a causal role in depression. The proinflammatory cytokines that have been identified most consistently in depression are IL-1, IL-6, and TNF-a.
Maes and his colleagues (2000) first identified increased inflammation as being related to depression and anxiety in postpartum women. When inflammation was initially identified as a risk factor for depression, it was generally seen as one of many: one that was comparable to risk factors such as low social support, maternal history of affective (emotional) disorders or trauma, infant illness or prematurity, or low socioeconomic status. More recent research, however, has revealed that stress of all types increases inflammation, and that inflammation is the likely mechanism by which the other risk factors lead to depression. This is true for depression in general and for postpartum depression in particular. These recent studies constitute an important shift in how we think about depression: inflammation is not simply a risk factor; it is the risk factor that underlies all the others.
Pregnant and postpartum women are particularly vulnerable to these effects because their inflammation levels normally rise during the last trimester of pregnancy -- a time when they are also at high risk for depression (Kendall-Tackett 2005; 2007). Inflammation serves several important functions in pregnant women including preparing their bodies for labor and protecting them against infection once the baby is born. However, in depressed women, inflammation levels are too high.
Depression can also influence the systems that normally keep inflammation in check. For example, the stress hormone cortisol is anti-inflammatory and is generally secreted when inflammation levels get too high. However, depressed people either have too much or too little cortisol. For example, Groër and Morgan (2007), in their study of 200 postpartum women, found that depressed women had abnormally low levels of cortisol at four to six weeks postpartum. Low levels of cortisol are not sufficient to control inflammation. Conversely, if women's cortisol levels are too high, they can be resistant to its effects in a process similar to insulin resistance. In either case, the net result is elevated inflammation.
Depression and Preterm Birth
Depression poses another health risk in pregnant women -- increased risk of preterm birth. Several researchers have noted that depression and posttraumatic stress disorder (PTSD) increase the risk of preterm birth, and inflammation may explain why. For example, in one large study of pregnant women in France, women who were depressed had more than twice the rate of preterm birth compared to non-depressed women. This was found even though the women were receiving regular prenatal care and were at low risk for preterm birth (Dayan et al. 2006). Proinflammatory cytokines help prepare the body for labor by ripening the cervix and causing contractions. If they are elevated because of depression, they appear to trigger preterm labor (Kendall-Tackett 2007).
Inflammation may also explain another set of findings regarding preterm birth. In a study of 291 low-income pregnant women, participants were randomly assigned to receive either DHA-enriched eggs or regular eggs that they were to eat daily during the last trimester of their pregnancy. DHA is a long-chain Omega-3 fatty acid with anti-inflammatory effects (see below). Women who received the DHA-enriched eggs had an average increase in gestation of six days (Smuts et al. 2003). The DHA-enriched eggs may have increased gestation length by decreasing inflammation.
Stressors that Increase Inflammation in Postpartum Women
Some common experiences of new motherhood are well-known risk factors for depression. These include sleep disturbances, pain, and psychological trauma. All three of these are also related to increased inflammation, as described below.
Sleep Disturbances and Fatigue: Both sleep disturbances and daytime fatigue are related to inflammation. When proinflammatory cytokine levels are high, fatigue increases. One study found that at four weeks postpartum, fatigued women had higher levels of IL-1‚ than women who were less fatigued. The authors speculated that IL-1‚ may have an indirect link to postpartum depression through fatigue (Corwin et al. 2003). Inflammation may also cause disturbed sleep, which increases the level of daytime sleepiness (Motivala et al. 2005).
Pain: The pain-inflammation connection is well-known and common pain medications (such as ibuprofen) are anti-inflammatory. Pain can also trigger depression in postpartum women. Nipple pain is one common type. A study of 113 breastfeeding women demonstrated that women with pain were significantly more likely to be depressed than women without pain (38 percent versus 14 percent). In addition, women with pain had significantly higher scores on the Profile of Mood States questionnaire. Once the pain resolved, scores on these scales dropped to normal levels (Amir et al. 1996).
Psychological Trauma: Psychological trauma can also increase the risk of both depression and posttraumatic stress disorder (PTSD). Trauma can be due to a previous event, such as a sexual assault or natural disaster, or it can be due to recent events (including birth). A woman with a history of depression or trauma is often more vulnerable to current life stresses than women without such a history. Kiecolt-Glaser and colleagues (2007) noted that stress and depression appear to "prime" the inflammatory response so that it is more reactive to subsequent stressors. Like depression, posttraumatic stress disorder (PTSD) also disrupts the normal stress response. Cortisol levels can be abnormally high or low. When cortisol is low, it doesn't inhibit the inflammatory response system. Even if cortisol is elevated, the receptors can be less sensitive to cortisol and fail to restrain the inflammatory response.
Implications: Goals of Prevention and Treatment
This new research suggests two important and related goals for the prevention and treatment of depression in new mothers: reduce maternal stress and reduce inflammation. These are described below.
Reduce Maternal Stress: Since stress triggers inflammation, the first goal for preventing or treating depression is to reduce maternal stress. And that's where breastfeeding comes in. Current research indicates that breastfeeding protects maternal mood -- when it is going well. And one way that it does this is by reducing stress. In a study of 28 mothers who were both breast- and bottle-feeding, researchers measured mothers' stress levels immediately before and after both types of feeding. The researchers found that breastfeeding decreased negative mood and bottle feeding decreased positive mood in the same women (Mezzacappa and Katkin 2002).
Groër (2005) compared stress levels of three groups of women: women who were exclusively breastfeeding, women who were exclusively formula feeding, and non-postpartum healthy volunteers. She found that breastfeeding women had lower perceived stress, depression, and anger, and more positive life events than the controls or formula-feeding mothers. She concluded that breastfeeding was mildly protective of maternal mood.
A study of 43 breastfeeding women found that breastfeeding significantly decreased the stress hormones ACTH and cortisol in response to a lab-induced stressor. Breastfeeding, and specifically suckling at the breast, provided a short-term suppression of the stress response (Heinrichs et al. 2001). The authors hypothesized that this short-term suppression provided several evolutionary and biological advantages. It isolated the mother from distracting stimuli, facilitated the woman's immune system, protected her baby from high cortisol in the milk, and prevented stress-related inhibition of lactation.
As mentioned earlier, there is one important caveat to these findings: mothers get the stress-lowering effects of breastfeeding only when it is going well. If there are problems, it increases stress levels and risk of depression (Amir et al. 1996).
Reduce Inflammation: The second recommendation for the prevention or treatment of depression is to reduce mothers' inflammation. One way to accomplish this is through consumption of the long-chain Omega-3 fatty acids: EPA and DHA. I've written about the protective effects of EPA and DHA in previous articles. What is new is our understanding of why they work: they specifically lower levels of proinflammatory cytokines.
Pregnant and breastfeeding women in many industrialized countries are deficient in EPA and DHA because their dietary intake is insufficient. Moreover, their babies need these fatty acids for their developing nervous systems. Writing about mothers in Australia, Rees and colleagues (2005) observed that babies need about 67 mg a day of DHA for their development during the last trimester of pregnancy. Unfortunately, Australian mothers consume about 15 mg a day -- well under what is required. Babies take what they need from maternal stores, and mothers' stores become further depleted with each pregnancy. And these deficiencies appear to increase mothers' vulnerability to depression.
EPA and DHA in Population Studies
Several recent population studies have found that people who consume more EPA and DHA (usually by eating fatty coldwater fish) have lower rates of several affective disorders including major depression, bipolar disorder, and suicide risk (Kendall-Tackett 2007). In a large population study, mothers who ate high amounts of seafood during pregnancy, and who had high levels of DHA in their milk postpartum, had lower levels of postpartum depression (Hibbeln 2002). These findings are likely due to EPA and DHA's anti-inflammatory characteristics. A recent population study in Italy found that people with high levels of EPA and DHA in their blood also had lower levels of proinflammatory cytokines (Ferruchi et al. 2006).
These population studies indicate that EPA and DHA may help prevent mood disorders. However, pregnant and breastfeeding women are advised to limit the amount of fish they eat (the prime source of these fatty acids) because of contaminants in seafood. Unfortunately, most mothers cannot safely eat enough seafood while pregnant or breastfeeding to achieve an anti-depressant effect. Mercury, PCBs, and other contaminants found in fish are highly toxic to babies' developing nervous systems, so it is important to find sources that are contaminant-free. These include fish-oil supplements, prenatal vitamins, and fortified foods. The US Pharmacopeia is one reliable and neutral source of information on brands of EPA and DHA that are safe for pregnant and breastfeeding women. The US Pharmacopeia tests for contaminants and has verified several brands of over-the-counter fish oil supplements (see www.USP.org for a listing). There are also other fortified foods, and vegetarian sources of DHA. A detailed listing of other products can be found at www.Breastfeeding MadeSimple.com. Both EPA and DHA are compatible with breastfeeding. ALA, the Omega-3 found in flax seed and other plant sources, does not prevent or treat depression (Bratman and Girman 2003; Kendall-Tackett 2005). It isn't harmful. It simply does not help with depression. The minimum recommended dosage is 200 to 400 mg of DHA for the prevention of depression and 1000 mg of EPA for treatment (in most studies, this was used in addition to medications, with or without DHA). Mothers should discuss these and any supplements with their health care providers before taking them.
Other Anti-Inflammatory Treatments for Depression
Interestingly, other treatments for depression that are known to work are also anti-inflammatory. For example, the herbal antidepressant St. John's Wort is anti-inflammatory, antibacterial, and antiviral (Balch 2002). Standard antidepressants also lower inflammation and this feature may partially explain their efficacy. For example, a recent study compared C-reactive protein levels in cardiac patients with major depression before and after treatment with antidepressants of the selective serotonin reuptake inhibitors, or SSRIs class (e.g., Zoloft, Paxil, Prozac). C-reactive protein is an acute-phase protein and another marker of inflammation. It is also a known risk factor for cardiovascular disease. In these patients, C-reactive protein dropped significantly after treatment, regardless of whether depression resolved (O'Brien et al. 2006).
Cognitive therapy is also arguably anti-inflammatory. Cognitive therapy helps clients recognize negative or untrue beliefs that they have about themselves or others, and to challenge those beliefs with the truth. In numerous clinical trials, researchers have found it as effective as medications for depression, anxiety, obsessive-compulsive disorder, and chronic pain (Rupke 2006). From a physiological standpoint, cognitive therapy may also lower inflammation. Two recent studies have demonstrated that negative beliefs, such as hostility, increase the levels of proinflammatory cytokines (Kiecolt-Glaser et al. 2005; Suarez et al. 2004). The primary goal of cognitive therapy is to reduce negative cognitions (perceptions; Rupke 2006). Reducing negative cognitions will most likely have physical effects as well -- primarily by reducing inflammation.
Recent research has identified inflammation is a key factor in depression, and it is triggered by both physical and psychological stress. Postpartum women are particularly at risk because their inflammation levels are already naturally elevated in the last trimester of pregnancy. And this elevation continues throughout the postpartum period. Two approaches may prevent depression or reduce its severity: lowering maternal stress and reducing inflammation. Breastfeeding has been shown to reduce stress and protect maternal mood -- when it's going well. For mothers who are having difficulties, promptly addressing breastfeeding problems can protect maternal mental health. In addition, since many treatments for depression are compatible with breastfeeding, it can be preserved in most cases.
Interventions that lower inflammation have efficacy in treating depression. Proactive use of anti-inflammatory treatments may also increase mothers' resilience to the stresses of new motherhood. This can prevent subsequent episodes of depression or at the very least, lessen its severity.
Leaders, as always, have an important part to play in helping mothers during the postpartum period and beyond. And there are several specific things you can do with regard to depression. I've listed some suggestions below that are within our scope of practice. But we must always be careful not to cross the line and give mothers medical advice.
1. We can affirmatively state that breastfeeding, because it lessens stress, protects mothers mental health. We can also help by quickly addressing breastfeeding problems (including making referrals when appropriate) as they increase mothers' risk.
2. If mothers are currently depressed, they might worry that they will "give" their babies depression by breastfeeding. Actually, the opposite is true. We can let them know that breastfeeding is protecting their babies from any potential harmful effects of their depression and is something good they can do for their babies while they recover.
3. We can give mothers "permission" to lower stress in their lives because it can trigger depression. So many mothers I meet, particularly in the US, labor under the delusion that they must go it alone and be everything to everyone. We can help them see that lowering stress will benefit both them and their families.
4. By using resources, such as the THE BREASTFEEDING ANSWER BOOK and Medications and Mothers' Milk, we can offer health care providers information about medications and breastfeeding. Most antidepressants are compatible with breastfeeding, and this information can be helpful for both the mother you are currently working with and for any other mothers that provider sees in the future.
5. We can refer mothers to sources of information on depression that are breastfeeding friendly. For example, Nancy Mohrbacher and I have a page on depression specifically for mothers on www.BreastfeedingMadeSimple.com, with links to other sites. The New Hampshire Breastfeeding Task Force also offers a free breastfeeding-friendly curriculum on postpartum depression, with accompanying handouts for mothers (www.NHBreastfeeding TaskForce.org).
6. Finally, we can be a source of emotional support and encouragement. Most of you have likely prevented many cases of depression in your work as Leaders. Mother-to-mother support remains a key tool for preventing depression. So just by doing the work you are doing, you are aiding in the fight against postpartum depression. Keep up the good work!
Amir, L.H., Dennerstein, L., Garland, S.M., et al. Psychological aspects of nipple pain in lactating women. J Psychosom Obstet Gyn 1996; 17: 53-58.
Balch, P. Prescription for Herbal Healing. New York: Avery, 2002.
Bratman, S., & Girman, A.M. Handbook of Herbs and Supplements and Their Therapeutic Uses. St Louis: Mosby, 2003.
Corwin, E.J., Bozoky, I., Pugh, L.C., et al. Interleukin-1beta elevation during the postpartum period. Ann Behav Med 2003; 5: 41-47.
Dayan, J., Creveuil, C., Marks, M.N., et al. Prenatal depression, prenatal anxiety, and spontaneous preterm birth: A prospective cohort study among women with early and regular care. Psychosom Med 2006, 68: 938-946
Ferrucci, L., Cherubini, A., Bandinelli, S., et al. Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrin Metab 2006; 91: 439-446.
Groër, M. Differences between exclusive breastfeeders, formula-feeders, and controls: A study of stress, mood, and endocrine variables. Biol Res Nurs 2005; 7: 106-117.
Groër, M.W., & Morgan, K. Immune, health and endocrine characteristics of depressed postpartum mothers. Psychoneuroendocrinology 2007; 32: 133-139.
Heinrichs, M., Meinlschmidt, G., Neumann, I., et al. Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial stress in postpartum lactating women. J Clin Endocrin Metab 2001; 86: 4798-4804.
Hibbeln, J.R. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: A cross-national, ecological analysis. J Affective Dis 2002; 69: 15-29.
Kendall-Tackett, K.A. A new paradigm for depression in new mothers: The central role of inflammation and how breastfeeding and anti-inflammatory treatments protect maternal mental health. Int Breastfeeding J 2007; Mar., www.InternationalBreastfeedingJournal.com
Kendall-Tackett, K.A. Depression in New Mothers. Binghamton, New York: Haworth, 2005.
Kiecolt-Glaser, J.K., Belury, M.A., Porter, K., et al. Depressive symptoms, omega-6: omega-3 fatty acids, and inflammation in older adults. Psychosom Med 2007; 69; 217-224.
Kiecolt-Glaser, J.K., Loving, T.J., Stowell, J.R., et al. Hostile marital interactions, proinflammatory cytokine production, and wound healing. Arch Gen Psychiatry 2005; 62: 1377-1384.
Maes, M, Lin, A-H, Ombelet, W., et al. Immune activation in the early puerperium is related to postpartum anxiety and depression symptoms. Psychoneuroendocrinology 2000, 25: 121-137.
Mezzacappa, E.S., & Katkin, E.S. Breastfeeding is associated with reduced perceived stress and negative mood in mothers. Health Psychology 2002; 21, 187-193.
Miller, G.E., Rohleder, N., Stetler, C., et al. Clinical depression and regulation of the inflammatory response during acute stress. Psychosom Med 2005; 67: 679-685.
Motivala, S.J., Safati, A., Olmos, L., et al. Inflammatory markers and sleep disturbance in major depression. Psychosom Med 2005; 67: 187-194.
O'Brien, S.M., Scott, L.V., & Dinan, T.G. Antidepressant therapy and C-reactive protein levels. Brit J Psychiatry 2006; 188: 449-452.
Rees, A-M., Austin, M-P., & Parker, G. Role of omega-3 fatty acids as a treatment for depression in the perinatal period. Aust NZ J Psychiatry 2005; 39: 274-280.
Rupke, S.J., Blecke, D., & Renfrow, M. Cognitive therapy for depression.Am Fam Physician 2006; 73: 83-86.
Smuts, C.M., Huang, M., Mundy, D., et al.A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy. Obstet Gynecol 2005; 101: 469-479.