Severe depression during and after pregnancy may be triggered by a runaway inflammatory immune response in some women, according to a new study published online in Brain, Behavior, and Immunity.
“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 study lead author Eric Achtyes, MD, a staff psychiatrist at Pine Rest Christian Mental Health Services and an associate professor at Michigan State University, both in Grand Rapids, Michigan.
“Hopefully, this study will allow us to develop treatments that more specifically target those who are at risk for an ‘inflammatory’ perinatal depression.”
Dr. Achtyes and colleagues analyzed blood samples from 165 women, some diagnosed with peripartum-onset depression. They identified several inflammatory factors that appeared to contribute to pregnancy-related depression: increased levels of inflammatory cytokines IL-6 and IL-8; decreased levels of IL-2, a cytokine important for immune function; and lower levels of serotonin. According to researchers, tryptophan is shunted toward the kynurenine pathway, which is linked with inflammation, instead of toward the production of serotonin, a chemical regulator of mood.
Women with lower serotonin levels were at increased risk for suicidal behavior, even after researchers adjusted for depression severity and psychosocial factors, the study found.
“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,” researchers wrote. “We propose that inflammatory cytokines and the kynurenine pathway are potential treatment targets in peripartum-onset depression, opening up the possibility of novel therapeutic strategies targeting the peripartum.”
Achtyes E, Keaton SA, Smart L, et al. Inflammation and kynurenine pathway dysregulation in post-partum women with severe and suicidal depression. Brain, Behavior, and Immunity. 2019 November 5;[Epub ahead of print].