Summary: Inflammatory factors appear to contribute to pregnancy-related depression onset and severity. Researchers found elevated levels of IL-6 and IL-8 and reduced levels of IL-2 in blood samples taken from blood samples of pregnant women who reported symptoms of depression. Additionally, they found serotonin was drastically reduced.
Source: Van Andel Research Institute
A runaway, inflammatory immune response may be responsible for triggering severe depression during and after pregnancy, according to a new study published in the journal Brain, Behavior and Immunit.
Not to be mistaken for the rapidly passing “baby blues,” which is common right after delivery, pregnancy-related depression is a serious medical condition that can escalate in severity and may even require hospitalization. One in five new mothers experience depression after pregnancy, with symptoms beginning during pregnancy and generally worsening after delivery. An estimated 14% have suicidal ideation during pregnancy.
“Pregnancy-related depression is common yet poorly understood,” said Lena Brundin, M.D., Ph.D., an associate professor at Van Andel Institute and senior author of the study. “Biologically speaking, pregnancy is a major inflammatory event that can upend many of the body’s day-to-day molecular processes. If we can better understand these irregularities, it could lead to new ideas about how best to treat perinatal depression.”
The team, which included researchers from Pine Rest Christian Mental Health Services and Michigan State University, analyzed blood samples from 165 patient volunteers at Pine Rest’s Mother and Baby Program and the Obstetrics and Gynecology Clinic at Spectrum Health in Grand Rapids.
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.
“Inflammation is an important and normal part of the immune system and, in early pregnancy, prevents the mother’s immune system from attacking the fetus. However, when the inflammatory reaction is protracted or more intense than is optimal, it may lead to worsening depression in a subset of vulnerable women,” said Eric Achtyes, M.D., M.S., staff psychiatrist at Pine Rest, an associate professor at Michigan State and the study’s lead author. “Hopefully, this study will allow us to develop treatments that more specifically target those who are at risk for an ‘inflammatory’ perinatal depression.”
In addition to Brundin and Achtyes, authors include Sarah A. Keaton, Ph.D., Amanda R. Burmeister, Ph.D., Patrick L. Heilman, Ph.D., Stanislaw Krzyzanowski and Martha L. Escobar Galvis, Ph.D. of Van Andel Institute; LeAnn Smart and Madhavi Nagalla, M.D., of Pine Rest Christian Mental Health Services; Gilles J. Guillemin, Ph.D., and Chai K. Lim, Ph.D., of Macquarie University; Maria Muzik, M.D., of University of Michigan; Teodor T. Postolache, M.D., Ph.D., of University of Maryland School of Medicine; and Richard Leach, M.D., of Michigan State University. Achtyes, Nagalla and Keaton also are affiliated with Michigan State University; Leach also is affiliated with Spectrum Health. Van Andel Institute’s Pathology and Biorepository Core and Bioinformatics and Biostatistics Core also contributed to this study.
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Funding: Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award no. R01MH104622 (Brundin). The content is solely the responsibility of the authors and does not necessarily represent the official views of any funding organization.
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Original Research: Closed access
“Inflammation and kynurenine pathway dysregulation in post-partum women with severe and suicidal depression”. Lena Brundin et al.
Brain, Behavior and Immunity doi:10.1016/j.bbi.2019.10.017.
Inflammation and kynurenine pathway dysregulation in post-partum women with severe and suicidal depression
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.