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 a powerful common-sense tools for health – for mom and baby.

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