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The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring.

ABSTRACT: While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offspring neurodevelopment is unclear. This study characterizes the placental and circulatory lipids in antenatal depression, as well as socio-emotional outcomes in the offspring. Targeted liquid chromatography-mass spectrometry covering 470 lipid species was performed on placenta from 186 women with low (n?=?70) or high (n?=?116) levels of antenatal depressive symptoms assessed using the Edinburgh Postnatal Depression Scale at 26 weeks' gestation. Child socio-emotional outcomes were assessed from the Child Behavior Check List (CBCL) at 48 months. Seventeen placental lipid species showed an inverse association with antenatal EPDS scores. Specifically, lower levels of phospholipids containing LC-PUFAs: omega-3 docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and omega-6 arachidonic acid (AA) were significantly associated with depressive symptoms. Additional measurement of LC-PUFA in antenatal plasma samples at mid-gestation confirmed the reduced circulation of these specific fatty acids in mothers. Reduced concentration of the placental phospholipids also predicted poorer socio-emotional outcomes in the offspring. This study provides new insights into the role of the materno-fetal lipid cross-talk as a mechanism linking maternal mental health to that of the offspring. These findings show the potential utility of nutritional approaches among pregnant women with depressive symptoms to reduce offspring risk for later socio-emotional problems.

SUBMITTER: Wong G

PROVIDER: S-EPMC7862650 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring.

Wong Gerard G Weir Jacquelyn M JM Mishra Priti P Huynh Kevin K Nijagal Brunda B Gupta Varsha V Broekman Birit F P BFP Chong Mary Foong-Fong MF Chan Shiao-Yng SY Tan Kok Hian KH Tull Dedreia D McConville Malcolm M Calder Philip C PC Godfrey Keith M KM Chong Yap Seng YS Gluckman Peter D PD Meaney Michael J MJ Meikle Peter J PJ Karnani Neerja N

Translational psychiatry 20210204 1

While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offsprin ...[more]

PMID: 33542173

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Project description:BackgroundResearch on parent-level factors linked to adolescent attachment security would inform interventions to prevent or reduce youth psychopathology and other negative outcomes. The current study examined one relevant parent-level variable: maternal interpersonal problems. Interpersonal problems, a key characteristic of personality pathology, are well described by the interpersonal circumplex (IPC) and have been shown to be associated with maladaptive adult attachment in close/romantic relationships; however, studies have not examined relationships with offspring attachment. Therefore, the first aim of the current study was to examine the relationship between maternal interpersonal problems and adolescent attachment insecurity. Based on previous evidence that parents' recalled bonding with caregivers is associated with the quality of bonding and attachment with offspring, the second aim was to examine whether mothers' recalled bonding with their own mothers partially explained this relationship.MethodsParticipants included 351 psychiatric inpatient adolescents (Mage = 15.26, 64.1% female) and their biological mothers. Logistic regressions tested whether maternal interpersonal problems were associated with Child Attachment Interview classifications (secure vs. insecure; secure vs. preoccupied vs. dismissing; not disorganized vs. disorganized). A mediation model (N = 210) tested whether the relationship between maternal interpersonal problems and adolescent attachment was mediated by the mother's recalled maternal bonding.ResultsMaternal interpersonal problems were associated with insecure (vs. secure), dismissing (vs. secure), and preoccupied (vs. secure) attachment. There was no significant relationship between maternal interpersonal problems and disorganized attachment. Mediation analyses showed that maternal interpersonal problems were indirectly related to adolescent attachment security via the mother's recalled maternal care, though only a small amount of variance (7%) in adolescent offspring attachment was accounted for by the model.ConclusionsResults provide the first evidence that maternal interpersonal problems are associated with higher likelihood of insecure attachment in adolescents. Therefore, researchers could consider drawing upon the IPC literature to further examine mechanisms of intergenerational risk and to tailor interventions aimed to improve parent-child relations and attachment. Additionally, findings highlight the mediating role of the mothers' recalled experiences with caregivers in the transmission of risk, suggesting attachment-based or mentalization-based interventions may be helpful for mothers with interpersonal problems and personality pathology.

Project description:IntroductionAntenatal depression is associated with a broad range of suboptimal outcomes in offspring, although the underlying mechanisms are not yet understood. Animal studies propose inflammation and glucocorticoids as mediators of the developmental programming effect of prenatal stress on offspring stress responses, but studies in humans are not yet at this stage. Indeed, to date no single study has examined the effects of a rigorously defined, clinically significant Major Depressive Disorder (MDD) in pregnancy on maternal antenatal inflammatory biomarkers and hypothalamic-pituitary (HPA) axis, as well as on offspring HPA axis, behavior and developmental outcomes in the first postnatal year.MethodsA prospective longitudinal design was used in 106 women (49 cases vs. 57 healthy controls) to study the effect of MDD in pregnancy and associated antenatal biology (inflammatory and cortisol biomarkers), on offspring stress response (cortisol response to immunization, at 8 weeks and 12 months), early neurobehavior (Neonatal Behavioral Assessment Scale, NBAS, at day 6), and cognitive, language and motor development (Bayley Scales of Infant and Toddler Development at 12 months).ResultsCompared with healthy controls, women with MDD in pregnancy had raised interleukin (IL) IL-6 (effect size (δ) = 0.53, p = 0.031), IL-10 (δ = 0.53, p = 0.043), tumor necrosis factor alpha (δ = 0.90, p = 0.003) and vascular endothelial growth factor (δ = 0.56, p = 0.008), together with raised diurnal cortisol secretion (δ = 0.89, p = 0.006), raised evening cortisol (δ = 0.64, p = 0.004), and blunted cortisol awakening response (δ = 0.70, p = 0.020), and an 8-day shorter length of gestation (δ = 0.70, p = 0.005). Furthermore, they had neonates with suboptimal neurobehavioral function in four out of five NBAS clusters measured (range of δ = 0.45-1.22 and p = 0.049-<0.001) and increased cortisol response to stress at one year of age (δ = 0.87, p < 0.001). Lastly, maternal inflammatory biomarkers and cortisol levels were correlated with infant stress response, suggesting a mechanistic link.ConclusionThis study confirms and extends the notion that depression in pregnancy is associated with altered offspring behavior and biological stress response, and demonstrates that changes in maternal antenatal stress-related biology are associated with these infant outcomes.

Project description:ObjectiveThe majority of studies that have examined parental alcohol use and offspring outcomes have either focused on exposure in the antenatal period or from clinical populations. This study sought to examine proximal and distal associations between parental alcohol use and offspring conduct problems and depressive symptoms in a population birth cohort.MethodsWe used prospective data from a large UK based population cohort (ALSPAC) to investigate the association between parental alcohol use, measured in units, (assessed at ages 4 and 12 years) with childhood conduct trajectories, (assessed on six occasions from 4 to 13.5 years, n = 6,927), and adolescent depressive symptoms (assessed on four occasions from ~13 to ~18 years, n = 5,539). Heavy drinking was defined as ?21 units per week in mothers and partners who drank 4+ units daily.ResultsWe found little evidence to support a dose response association between parental alcohol use and offspring outcomes. For example, we found insufficient evidence to support an association between maternal alcohol use at age 4 years and childhood conduct problems (childhood limited: OR = 1.00, 95% CI = .99, 1.01; adolescent onset: OR = 0.99, 95% CI = .98, 1.00; and early-onset persistent: OR = 0.99, 95% CI = .98, 1.00) per 1-unit change in maternal alcohol use compared to those with low levels of conduct problems. We also found insufficient evidence to support an association between maternal alcohol use at age 4 years and adolescent depressive symptoms (intercept: b = .001, 95% CI = -.01, .01, and slope: b = .003, 95% CI = -.03, .03) per 1-unit change in maternal alcohol use. Results remained consistent across amount of alcohol consumed (i.e., number of alcohol units or heavy alcohol use), parent (maternal self-reports or maternal reports of partner's alcohol use), and timing of alcohol use (assessed at age 4 or age 12 years).ConclusionsThere is no support for an association between parental alcohol use during childhood and conduct and emotional problems during childhood or adolescence.

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The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring.

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The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring.

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