Identifying a biological signature of prenatal maternal stress

Abstract

Psychological stress affects maternal gastrointestinal (GI) permeability, leading to low-grade inflammation, which can negatively affect fetal development. We investigated a panel of circulating markers as a biological signature of this stress exposure in pregnant women with and without the stress-related GI disorder irritable bowel syndrome (IBS). Markers of GI permeability and inflammation were measured in plasma from healthy and IBS cohorts of women at 15 and 20 weeks’ gestation. Biomarkers were evaluated with respect to their degree of association to levels of stress, anxiety, and depression as indicated by responses from the Perceived Stress Scale, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale. High levels of stress were associated with elevations of soluble CD14, lipopolysaccharide binding protein (LBP), and tumor necrosis factor–α, while anxiety was associated with elevated concentrations of C-reactive protein (CRP) in otherwise healthy pregnancies. Prenatal depression was associated with higher levels of soluble CD14, LBP, and CRP in the healthy cohort. High levels of prenatal anxiety and depression were also associated with lower concentrations of tryptophan and kynurenine, respectively, in the IBS cohort. These markers may represent a core maternal biological signature of active prenatal stress, which can be used to inform intervention strategies via stress reduction techniques or other lifestyle approaches. Such interventions may need to be tailored to reflect underlying GI conditions, such as IBS.

Inflammatory biomarkers and perinatal depression: a systematic review

“…Higher cerebrospinal fluid IL-1b, IL-23 and IL-33 concentrations at pre-cesarean time were significantly associated with increased odds of perinatal depression (37). Higher levels of TNF-α in depressed pregnant women were found when compared to controls in three studies (35, 38, 41). Nevertheless, these findings were not similar across all studies.…”

“…In general, higher levels of mostly pro-inflammatory markers (namely, CRP, IFN-γ/IL-4 ratio, IL-1β, IL-1R, IL-5, IL-6, IL-8, IL-9, IL-12, IL-13, IL-23, IL-33 and TNF-α) were associated to higher depressive symptomatology or observed in depressed groups. For example, groups with higher depression symptoms demonstrated significantly higher circulating CRP levels (41) in comparison with those with lower depression symptom scores. Increased levels of CRP were also observed in a group with depression and trauma, in comparison to healthy pregnant volunteers (39).…”

“…In respect to markers representing the tryptophan kynurenine pathway, e.g. tryptophan (TRP) and/or kynurenine (KYN) and/or the ratio KYN/TRP were assessed in ten studies: two during pregnancy (41,46); seven involving both pregnancy and postpartum (3,4,(47)(48)(49)(50)(51); and one at postpartum (52). Findings point out some mixed results, considering the assessment time point considered and the statistical associations studied.…”

The Role of the Kynurenine Pathway in the (Patho) physiology of Maternal Pregnancy and Fetal Outcomes: A Systematic Review

“…31,36 Three cohort studies investigated tryptophan and kynurenine in relation to levels of anxiety. 32,34,35 None of these studies found an association between tryptophan or kynurenine and anxiety symptoms during pregnancy. In all 3 studies the state of anxiety was measured using the State-Trait Anxiety Inventory (STAI).…”

Embryonic Exposure to Tryptophan Yields Bullying Victimization via Reprogramming the Microbiota-Gut-Brain Axis in a Chicken Model

“…Tryptophan (Trp), as an essential amino acid, is mainly derived from the diet in the small intestine and, as the sole precursor of serotonin (5-HT), is directly and indirectly involved in modulating brain function [ 5 ], which plays a critical role in developing social-emotional behaviors in offspring [ 6 ]. The altered Trp metabolism is one of the core biological signatures of prenatal maternal stress [ 7 ] caused by intrauterine inflammation, increasing the potential risk of neurodevelopmental disorders (NDDs), such as autism spectrum disorders (ASD) [ 8 ], which is closely related to bullying in youth [ 9 , 10 , 11 ]. Urinary Trp and purine metabolites are consistently upregulated in the gestational diabetes mellitus patients [ 12 ], and excessive Trp compromises pregnancy, e.g., pre-eclampsia [ 13 ].…”