Maternal inflammation during pregnancy and offspring psychiatric symptoms in childhood: Timing and sex matter

Giollabhui, Naoise Mac; Breen, Elizabeth C.; Murphy, Shannon; Maxwell, Seth D.; Cohn, Barbara A.; Krigbaum, Nickilou Y.; Cirillo, Piera M.; Perez, Christian; Alloy, Lauren B.; Drabick, Deborah A. G.; Ellman, Lauren M.

doi:10.1016/j.jpsychires.2019.01.009

Cited by 57 publications

(52 citation statements)

References 50 publications

(67 reference statements)

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“…These findings align with a recent study in humans which showed that elevated maternal cytokine levels in the first and second trimesters of pregnancy were associated with increased internalizing and externalizing symptoms in children. This study also found that gestational timing of inflammation and the child's sex can influence behavioural outcomes 55 . The current study did not consider gestational timing; however, the immune conditions included here are chronic, rather than acute, in nature.…”

Section: Discussionsupporting

confidence: 54%

“…The type and timing of MIA during pregnancy has been noted as an important factor which might exert differential effects on neurodevelopment 55,82,83 . Different types of MIA may utilize different immune molecules and pathways.…”

Section: Discussionmentioning

confidence: 99%

“…These findings are reflected in the incidence rate of ASD with four times more human males 1 being affected and higher rates of repetitive behaviour are found in males, compared to females 53,54 . A recent study in humans also showed that the child's sex, along with gestational timing of maternal inflammation (measured by elevated pro-inflammatory cytokines), can contribute to differential behavioural outcomes in the child 55 . While males appear to be more vulnerable to a maternal inflammation-mediated expression of neurodevelopmental difficulties, the mechanisms underlying this association remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…infection vs. chronic diseases such as autoimmunity, or asthma), the timing (i.e. early vs. late gestation), the duration (short vs. episodic/continuous exposures), and severity of the MIA, to produce differential behavioural outcomes in males and females 55 – 57 .…”

Section: Introductionmentioning

confidence: 99%

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Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity

et al. 2020

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Epidemiological and animal research shows that maternal immune activation increases the risk of autism spectrum disorders (ASD) in offspring. Emerging evidence suggests that maternal immune conditions may play a role in the phenotypic expression of neurodevelopmental difficulties in children with ASD and this may be moderated by offspring sex. This study aimed to investigate whether maternal immune conditions were associated with increased severity of adverse neurodevelopmental outcomes in children with ASD. Maternal immune conditions were examined as predictors of ASD severity, behavioural and emotional well-being, and cognitive functioning in a cohort of 363 children with ASD (n = 363; 252 males, 111 females; median age 3.07 [interquartile range 2.64-3.36 years]). We also explored whether these outcomes varied between male and female children. Results showed that maternal asthma was the most common immune condition reported in mothers of children with ASD. A history of maternal immune conditions (p = 0.009) was more common in male children with ASD, compared to female children. Maternal immune conditions were associated with increased behavioural and emotional problems in male and female children. By contrast, maternal immune conditions were not associated with decreased cognitive function. The findings demonstrate that MIA may influence the expression of symptoms in children with ASD and outcomes may vary between males and females.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity

et al. 2020

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“…For instance, the proinflammatory cytokine IL-1β negatively regulates hippocampal neurogenesis, suggesting a possible mechanism through which chronic inflammation could affect schizophrenia susceptibility ( 79 ). Notably, maternal inflammation correlates with later childhood psychiatric symptoms ( 80 ). Other potential risk pathways include effects from maternal fever, maternal antibodies crossing the placenta and medications, such as analgesics and anti-inflammatories, taken by the mother during infection, all of which may impact fetal neurodevelopment ( 81 – 83 ).…”

Section: Perinatal Developmentmentioning

confidence: 99%

Considering the Microbiome in Stress-Related and Neurodevelopmental Trajectories to Schizophrenia

et al. 2020

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Early life adversity and prenatal stress are consistently associated with an increased risk for schizophrenia, although the exact pathogenic mechanisms linking the exposures with the disease remain elusive. Our previous view of the HPA stress axis as an elegant but simple negative feedback loop, orchestrating adaptation to stressors among the hypothalamus, pituitary, and adrenal glands, needs to be updated. Research in the last two decades shows that important bidirectional signaling between the HPA axis and intestinal mucosa modulates brain function and neurochemistry, including effects on glucocorticoid hormones and brain-derived neurotrophic factor (BDNF). The intestinal microbiome in earliest life, which is seeded by the vaginal microbiome during delivery, programs the development of the HPA axis in a critical developmental window, determining stress sensitivity and HPA function as well as immune system development. The crosstalk between the HPA and the Microbiome Gut Brain Axis (MGBA) is particularly high in the hippocampus, the most consistently disrupted neural region in persons with schizophrenia. Animal models suggest that the MGBA remains influential on behavior and physiology across developmental stages, including the perinatal window, early childhood, adolescence, and young adulthood. Understanding the role of the microbiome on critical risk related stressors may enhance or transform of understanding of the origins of schizophrenia and offer new approaches to increase resilience against stress effects for preventing and treating schizophrenia.

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Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Lipner,

Mac Giollabhui,

Breen

et al. 2024

JAMA Psychiatry

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ImportancePrenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined.ObjectiveTo determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations.Design, Setting, and ParticipantsThis was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023.ExposuresLevels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy.Main Outcomes and MeasuresSelf-reported depressive symptoms at adolescent follow-up.ResultsA total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75).Conclusions and RelevanceIn this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

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Maternal inflammation during pregnancy and offspring psychiatric symptoms in childhood: Timing and sex matter

Cited by 57 publications

References 50 publications

Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity

Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity

Considering the Microbiome in Stress-Related and Neurodevelopmental Trajectories to Schizophrenia

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

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