Inflammation and kynurenine pathway dysregulation in post-partum women with severe and suicidal depression, 2019, Achtyes et al

[rvallee]

https://www.sciencedirect.com/science/article/pii/S0889159119310773

Highlights

• Severe peripartum depression (PPD) with suicidality is an understudied disorder.

• Severe depression in the post-partum involves dysregulation of the immune response.

• Tryptophan is shunted towards the kynurenine pathway instead of serotonin production.

• Women with reduced plasma serotonin are at an increased risk for suicidal behavior.

• Inflammation and the kynurenine pathway may be treatment targets in severe PPD.

Abstract
Depression during pregnancy and the post-partum is common, with severe cases resulting in suicidal behavior. Despite the urgent and unmet medical need, the biological underpinnings of peri-partum depression remain unclear. It has been suggested that it is triggered by dynamic changes of the immune system during pregnancy and at delivery. Therefore, we investigated whether a pro-inflammatory status in plasma, together with changes in the kynurenine pathway activity, is associated with the development of severe depression and suicidal behavior in the post-partum. Our cross-sectional study targets a unique, understudied population in which the pronounced severity of symptoms required hospitalization.

We analyzed plasma IL-1β, IL-2, IL-6, IL-8, TNF-α, tryptophan, serotonin, kynurenine, nicotinamide, quinolinic- and kynurenic acids in post-partum women diagnosed with peripartum onset depression (PPD) and healthy controls (n = 165). We assessed depression severity using the Edinburgh Postnatal Depression Scale and suicidality using the Columbia-Suicide Severity Rating Scale.

We found that increased plasma IL-6 and IL-8 and reductions of serotonin, IL-2 and quinolinic acid were associated with the severity of depressive symptoms and increased the risk for PPD. Moreover, women with lower serotonin levels were at an increased risk for suicidal behavior, even when adjusting for depression severity, psychosocial factors, age BMI, and medication.

Our results indicate that severe depression in the post-partum involves dysregulation of the immune response and the kynurenine pathway, with a concomitant reduction in serotonin levels. We propose that inflammatory cytokines and the kynurenine pathway are potential treatment targets in PPD, opening up the possibility of novel therapeutic strategies targeting the peripartum.

From a press release by the university: https://www.vai.org/pregnancy-related-depression-lena-brundin/

They found that several inflammatory factors appear to contribute to pregnancy-related depression onset and severity. Levels of IL-6 and IL-8 — both inflammatory chemicals called cytokines — were elevated while levels of another cytokine called IL-2, which plays an important role in immune function, were low. At the same time, there was a drastic reduction in serotonin, an important chemical regulator of mood.

These changes point to alterations in the way a molecular building block called tryptophan, which is required for serotonin production, is hijacked and shunted away by the kynurenine pathway, a molecular cascade closely linked to inflammation. The resulting loss of serotonin tracks with depressive symptom intensity; the less serotonin, the more severe the symptoms.

Hello tryptophan my old friend.


I frankly find it doubtful that cognition, thoughts and beliefs, play more than a minor role, if at all, in the vast majority of depression. If it does it's probably trivial. Far too many happy people with everything going on for them developed it. Meanwhile this pathological thinking has probably discouraged many potential avenues because of a certainty over a critical role of psychology, especially thoughts and behaviors.

That hypothesis makes little sense and frankly looking at the BPS obsession over those and how convinced they are they play a role only reinforces that. Their beliefs almost seem like a standard bearer that the opposite is more likely to be true.

And beyond that very likely that nearly all, if not absolutely all, of the maligned chronic diseases have similar causes, in the immune system though involving different mechanisms in response to pathogens, toxins, pollution or repeated infections.

I really hope that this here leads to better handling of PPD, especially shedding off the misguided beliefs that formed all earlier thinking.

 

[wastwater]

http://www.cytokines-and-depression.com/