Fire In The Belly


What goes wrong for the 10-15% of women who feel like hiding under the covers instead of gazing blissfully into their newborns peaceful face?  Is it expectations unmet?  Is it hormones?  Is it the brain? Having spent several years treating these women, I believe that what we are calling postpartum depression and anxiety is in fact postpartum immune dysfunction, and its attendant inflammation. The relationship between endocrine and immune variables in the postpartum period, in women with depression, anxiety, and psychosis, has yet to be clarified.  Several years of preliminary work have focused on the premise that these affected women experience suppression of the hypothalamic-pituitary axis (free cortisol and corticotropin releasing hormone) more severely and extensively than “normal” controls.  In states of low cortisol (or low hypothalamic activity), inflammation, infection, and autoimmunity are more likely.  Specifically, studies have noted that macrophages are activated and TH1 cells are suppressed, suggesting that this aberrant immune response may be a significant driving force in the presentation of altered mood states.

A relatively recent discovery is the psychoneuroimmunologic bridge – the kynurenine pathway.

In animal and clinical research, the kynurenine/tryptophan ratio has been used as a marker of inflammation correlated with postpartum depressive behaviors and states.  Inflammatory messengers, or cytokines IL6 and TNFalpha, have been demonstrated to be elevated in the cerebrospinal fluid of women at the time of their childbirth who then presented with depression at 6 weeks postpartum.  Similarly, elevated levels of IL-1B predicted depressive symptoms at one month postpartum.  In the non-pregnant population, inflammatory underpinnings of depressive illness (cytokines, chemokines, reactive proteins, adhesion molecules) have been well-established, and anti-inflammatory interventions have been explored.   Among other disruptive behaviors, these inflammatory agents induce the enzyme indoleamine 2,3-dioxygenase, which “steals” tryptophan in the production of kynurenine, resulting in a net decrease in the almighty serotonin.  Cortical cells appear to specifically covert kynurenine to kynurenic acid, which acts to decrease activity through acetylcholine antagonism.  Meanwhile, in the amygdala, primitive impulses may go unchecked secondary to NMDA receptor agonism by quinolinic acid.  A brilliant review of this theory proposes that this sequence of unfortunate events may account for the intrusive violent images and impulses that often accompany postpartum mental pathology.

An area of innovative speculation is looking at the role of melatonin as a treatment intervention in the third trimester and postpartum.  If serotonin is compromised by inflammation or dietary insufficiency of tryptophan, melatonin will be as well.  Melatonin plays a pivotal role in sleep onset and maintenance, but perhaps of equal importance, as a powerful antioxidant line of defense.

So what can we do about all this inflammation? One thing we can do is to minimize stoking the flames of this system further.  We, as citizens of the first world, are awash in a particular type of immune sabotage: the Teflon we cook with, our fire-retardant coated carpets and furniture, our fluoridated water laced with pharmaceuticals, pesticides and GMOs in our food (which has been processed beyond all recognition).  In fact, a study of umbilical cord samples of a random population of newborns demonstrated the presence of 287 chemicals, 217 of which are toxic to the nervous system directly, let alone their perturbation of a delicately calibrated immune system that is just beginning to learn “self” from “other”.

Our most important interface between self and the environment is the gut.  The vagus nerve appears to be the primary conduit between the 200-600 million nerve cells in our enteric or intestinal nervous system and our central nervous system.  Stimulation and function of these cells is directly effected by the population of bacteria that nourish the enterocytes, promote immune tolerance, and alert us of danger.  While our intestinal microbiome is determined by our mode of birth delivery (c-section vs vaginal birth), whether we were breastfed,  and early exposures through environment and diet, it is ever modifiable through macro and micronutrients, stress, and supplementation.  In fact, clinical investigation into the beneficial effects of probiotics (lactobacillus and bifidobacterium) on mood and anxiety have suggested that probiotics may promote anti-inflammatory responses through IL10 activation, and alleviate anxiety.

While exercise, relaxation response, and targeted supplementation of the postpartum patient with anti-inflammatory nutrients (such as turmeric, probiotics, and melatonin) have not been formally studied, promoting immune system balance through minimization of lifestyle-related sources of inflammation (i.e. sugar, trans fats, stress, poor sleep, toxic chemical exposures) represent powerful common-sense tools for health – for mom and baby.


Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.


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  1. Check out JR Hibbeln on omega-3 deficits accounting for post-partum depression. According to Hibbeln, omega-3s get diverted to fetus (where they play major roles in developing the nervous system) resulting in deficits in moms. Hibbeln has supplemented omega-3s and therein lowered risk for post-partum depression. Charles Serhan has shown that omega-3s get converted to resolvins which place a break on the immune system. (Charles Serhan is prolific-recent reviews are thorough). With regard to the indolamine 2,3 deoxygenase story, this enzyme is also the drive on T reg production, which are major breaks on inflammation. Moreover, studies suggest that it’s the kynurenine that is directly the culprit in inducing depression without the serotonin being an issue. (reviewed in littrell, Frontiers in Psychology-it’s downloadable.)

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  2. Don’t forget that “postpartum depression,” like all of the invented DSM “disorders,” is not a single entity – it is an effect that could have a large number of causes, not just one. Omega-3 deficits are probably involved in some cases, and completely absent in others.

    Psychosocial factors also play a huge role in this phenomenon, and are almost always given short shrift. For instance, such changes as loss of income, loss of employment, need to return to employment prematurely, shifts in expectations from partner, changes in sexual activity, loss of sleep, nutritional demands of nursing, and re-emergence of childhood abuse issues are extremely common, and all can be very significant contributing factors to depression or anxiety following birth. That list could be expanded.

    Additionally, it is a well-known but massively underpublicized fact that domestic abuse frequently begins or escalates during or after a pregnancy, either because the new mother is now more dependent and more vulnerable and hence safer to attack, or because having to “share” a partner’s attentions with the new baby leads to a narcissistic partner becoming jealous and hostile toward the new mother. In any case, screening for domestic abuse should be an automatic part of any assessment of “postpartum depression” before a physiological cause is assumed to be primary, because it is a VERY common phenomenon in our culture, affecting over 1/10 of all women at any given time, and up to 1/3 over the course of a lifetime.

    Depression is very complex and not reducible to either simple brain chemistry or simple nutritional causes or treatments. It requires an individualized and thorough assessment of the person who is having the experience, including a wide range of both physiological and psychosocial factors.

    —- Steve

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  3. And, please, let us not forget the relationship, found in studies, between post-partum depression and the new mother feeling socially isolated and not having assistance at home with the infant.

    This is another symptom of nuclear families living apart from the extended family, long-time community ties, and traditional support systems. No wonder new mothers feel overwhelmed.

    What prospective mothers might very well need is friends like them. They should be guided into peer support networks as part of their prenatal care.

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  4. Is it possible this could be related to the sudden onset of intense food allergies post-partum? I have a close friend this happened to. There were intense life stressors after the birth and she developed very bad gluten sensitivity and a host of other allergies that actually expanded over time–now includes all nuts, soybeans, some vegetables and fruits. Really rough, she was seriously, clinically malnourished, lost a great deal of weight, and was told it was psychosomatic by her doctor. She finally figure out what it was but not until at least six months of very rough times. Is generally pretty good now with food restrictions, but their are occasional scares (she’s had very rapid and intense anaphyllactic shock a few times) and the diet is, well, not a lot of fun! Anyway, I’ve heard of this sort of rapid flip into hyper-allergic state after childbirth a few other times and wonder if there might be some relation to what you describe here. Many thanks for the article! DS

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  5. I suffered post-partum psychosis. My case was complex, as Stephen Gilbert suggests. It was a combination of exhaustion and unresolved childhood issues, and a spiritual crisis.

    But as Altostrata rightly suggests, the remedy can be as simple as a caring support community rallying around, as happened in my case.My church functioned in a very nurturing way. My best friend took the other children(not the infant) and I had a week of bedrest and journalling. My husband was also a wonderful support. This combination of prayer and rest was the only prescription I needed, and served to heal me completely, both body and soul. A program of cognitive therapy was able to help me in follow-up, to eliminate the “stinking thinking” and deal well with the unresolved issues from childhood traumas that had pushed me over the edge.

    I am very thankful that I was not forced on meds, as my psychosis was very florid, and it happened just before the Andrea Yates tragedy.

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