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Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Differential Effects of Prenatal Depression and Anxiety on Infant Sleep: Dual-Pathway Mechanisms Involving the HPA
Can Liu1,2, Yuan Lin3, Ye Li1,2
1School of Public Health, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
Insights
Prenatal depression increases infant sleep problems, partly mediated by cortisol. Prenatal anxiety impacts infant gut microbes and tryptophan, affecting sleep via a gut-brain axis pathway.
Area of Science:
- Perinatal mental health
- Infant sleep science
- Gut microbiome research
- Tryptophan metabolism
Background:
- Prenatal psychological distress is linked to adverse infant outcomes, including sleep disturbances and altered gut microbiota.
- The specific mediating roles of the neonatal gut microbiome and tryptophan metabolism in these associations are not well understood.
Purpose of the Study:
- To investigate the mediating roles of neonatal gut microbiome and tryptophan metabolism in the relationship between prenatal psychological distress (anxiety and depression) and infant sleep disturbances.
- To identify distinct pathways linking maternal prenatal mental health to infant sleep outcomes.
Main Methods:
- Prospective birth cohort study of 2288 mother-infant pairs.
- Assessment of prenatal anxiety/depression and infant sleep via questionnaires up to 12 months.
- Multi-omics analyses (16S rRNA sequencing for meconium microbiota, LC-MS/MS for cord blood tryptophan metabolites) in a 112-pair sub-cohort.
- Statistical analyses including LASSO regression, mediation analyses, and XGBoost modeling.
Main Results:
- Prenatal depression was a significant risk factor for infant sleep disturbance (OR=1.53), with a stronger effect in female infants.
- Cord blood cortisol partially mediated the link between prenatal depression and infant sleep disturbance.
- Prenatal anxiety was associated with reduced gut microbial diversity and Bifidobacterium, and decreased 3-HAA/serotonin levels, which were linked to sleep disturbance.
- Serial mediation analysis confirmed a pathway involving gut microbiota and tryptophan metabolism influencing sleep.
- XGBoost model predicted sleep disturbance with an AUC of 0.727, highlighting microbial diversity, Streptococcus, dopamine, and 3-HAA as key predictors.
Conclusions:
- Distinct mediating pathways link prenatal depression (via cortisol) and anxiety (via gut microbiome and tryptophan metabolism) to infant sleep disturbances.
- These findings offer potential targets for developing personalized interventions to improve infant sleep health.
Study Objectives:
Prenatal psychological distress is associated with adverse offspring outcomes, including infant sleep disturbances and altered gut microbiota, yet the mediating roles of neonatal gut microbiome and tryptophan metabolism remain underexplored.
Methods:
This prospective birth cohort study enrolled 2288 mother-infant pairs, using questionnaires to assess prenatal anxiety/depression and infant sleep patterns up to 12 months. A 112-pair sub-cohort underwent multi-omics analyses: meconium microbiota profiling via 16S rRNA sequencing and cord blood tryptophan metabolite quantification via LC-MS/MS. LASSO regression, mediation analyses, and XGBoost modeling were applied.
Results:
Results showed prenatal depression-only was a significant risk factor for infant sleep disturbance (fully adjusted OR = 1.53, 95% CI:1.04-2.25), with a stronger effect in female infants (OR = 2.11, p = 0.022). Cord blood cortisol partially mediated this link (ACME = -7.47, 95% CI: [-14.82, -0.12], p = 0.048). Prenatal anxiety correlated with reduced meconium microbial alpha-diversity, lower Bifidobacterium abundance, and decreased 3-HAA/serotonin levels, which were associated with sleep disturbance; serial mediation confirmed the gut microbiota-tryptophan metabolism pathway. The XGBoost predictive model achieved an AUC of 0.727, with microbial diversity, Streptococcus abundance, dopamine, and 3-HAA as top contributors.
Conclusions:
This study identifies distinct mediating pathways for depression and anxiety, providing targets for personalized infant sleep health interventions.
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