Social buffering of the maternal and infant HPA axes: Mediation and moderation in the intergenerational transmission of adverse childhood experiences.

Supportive social relationships can reduce both psychological and physiological responses to stressful experiences. Recently, studies have also assessed the potential for social relationships to buffer the intergenerational transmission of stress. The majority of these studies, however, have focussed on social learning as a mechanism responsible for the intergenerational transmission of stress. Evidence of biological mechanisms is lacking. The objective of the current study was, therefore, to determine whether the association between maternal adverse childhood experiences (ACEs) and infant hypothalamic-pituitary-adrenal (HPA) axis function is mediated by maternal HPA axis function during pregnancy and moderated by social support. Data were from 243 mother-infant dyads enrolled in a prospective longitudinal cohort (the Alberta Pregnancy Outcomes and Nutrition Study). Maternal history of ACEs was retrospectively assessed while maternal perceived social support and salivary cortisol were assessed prospectively at 6-22 weeks gestation (Time 1) and 27-37 weeks gestation (Time 2), and infant cortisol reactivity to a laboratory stressor and maternal perceived social support were assessed at 5-10 months postnatal (Time 3). Results revealed that maternal HPA axis function during pregnancy mediated the effects of maternal ACEs on infant HPA axis reactivity, suggesting that the maternal HPA axis is a mechanism by which maternal early life stress is transmitted to offspring. Furthermore, social support in the prenatal and postnatal periods moderated the cascade from maternal ACEs to infant HPA axis reactivity. Specifically, prenatal social support moderated the association between ACEs and maternal HPA axis function during pregnancy, and postnatal social support moderated the association between maternal HPA axis function and infant cortisol reactivity. These findings highlight the social sensitivity of the HPA axis and suggest the utility of social relationships as an intervention target to reduce the effects of maternal early life stress on infant outcomes.

Biological embedding of perinatal social relationships in infant stress reactivity.

Whereas significant advances have been made in understanding how exposure to early adversity "gets under the skin" of children to result in long term changes in developmental outcomes, the processes by which positive social relationships become biologically embedded remain poorly understood. The aim of this study was to understand the pathways by which maternal and infant social environments become biologically embedded in infant cortisol reactivity. Two hundred seventy-two pregnant women and their infants were prospectively assessed during pregnancy and at 6 months postpartum. In serial mediation analyses, higher perceived social support from partners during pregnancy was associated with lower infant cortisol reactivity or larger decreases in cortisol in response to a stressor at 6 months of age via lower self-reported prenatal maternal depression and higher mother-infant interaction quality. The findings add to our understanding of how perinatal social relationships become biologically embedded in child development.

Developmental origins of infant stress reactivity profiles: A multi-system approach.

BACKGROUND: This study tested the hypothesis that maternal physiological and psychological variables during pregnancy discriminate between theoretically informed infant stress reactivity profiles. METHODS: The sample comprised 254 women and their infants. Maternal mood, salivary cortisol, respiratory sinus arrhythmia (RSA), and salivary α-amylase (sAA) were assessed at 15 and 32 weeks gestational age. Infant salivary cortisol, RSA, and sAA reactivity were assessed in response to a structured laboratory frustration task at 6 months of age. Infant responses were used to classify them into stress reactivity profiles using three different classification schemes: hypothalamic-pituitary-adrenal (HPA)-axis, autonomic, and multi-system. Discriminant function analyses evaluated the prenatal variables that best discriminated infant reactivity profiles within each classification scheme. RESULTS: Maternal stress biomarkers, along with self-reported psychological distress during pregnancy, discriminated between infant stress reactivity profiles. CONCLUSIONS: These results suggest that maternal psychological and physiological states during pregnancy have broad effects on the development of the infant stress response systems. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 578-599, 2016.

CRYAB modulates the activation of CD4+ T cells from relapsing-remitting multiple sclerosis patients.

BACKGROUND: Suppression of activation of pathogenic CD4(+) T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. OBJECTIVE: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. METHODS: CD4(+) T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73-92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. RESULTS: The secretion of pro-inflammatory cytokines by CD4(+) T cells was decreased in the presence of CRYAB in a subset of relapsing-remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8(+) T cells, in CD4(+) T cells of MS patients that displayed suppressed cytokine production (responders). CONCLUSION: CRYAB may be capable of suppressing the activation of CD4(+) T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

Parental Use of "Cry Out" in a Community Sample During the First Year of Infant Life.

OBJECTIVE: The primary objective was to identify the characteristics of parents and infants and parenting practices associated with delayed responsiveness to infant crying during the first year of infant life. A secondary objective was to evaluate, in a subsample of maternal-infant pairs, the associations between delayed responsiveness to infant crying and observational measures of maternal-infant interaction and infant-maternal attachment. METHOD: This is a secondary analysis of the data from a community sample of pregnant women recruited to the Alberta Pregnancy Outcomes and Nutrition study. Mothers completed questionnaires during the first year of infant life (n = 1826), and a convenience subsample of maternal-infant pairs (n = 137) participated in laboratory assessments of maternal-infant interaction at 6 months of age and infant-maternal attachment at 20 months. RESULTS: Parental use of "cry out" as a strategy to deal with a crying infant was associated with parental characteristics (being white and having a relatively higher income), infant characteristics (higher problematic behavior at 3 months and reduced problematic behavior at 12 months), sleep ecology (infants sleeping alone), and parental soothing strategies (less frequently taking the infant into the parent's bed, cuddling, or carrying the crying infant). Cry out was not associated with observational measures of maternal sensitivity or infant-maternal attachment. CONCLUSION: When used selectively and in response to the specific needs and characteristics of the infant, delayed responsiveness may reduce problematic behavior and does not harm the infant's socioemotional development.

Partner social support during pregnancy and the postpartum period and inflammation in 3-month-old infants.

Prenatal social stress "programs" offspring immune activity in animal models, but how the prenatal social environment affects human offspring inflammation is not known. Here, we test associations between prenatal partner support quality, i.e. positive/helpful support, negative/upsetting support, and their interaction, and infant inflammatory markers. A sample of 113 women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort were followed from early pregnancy to 3-months postpartum. Partner support quality was measured during pregnancy and the postpartum period. Three-month-old infant blood samples were assayed for inflammatory markers, i.e., adaptive immune markers IFNγ, IL12p70 and IL10. The prenatal positive-by-negative partner support interaction predicted infant IFNγ, IL12p70, and IL10, p's<.035, independent of covariates and postpartum partner support. When negative partner support was high, high positive support predicted higher infant IFNγ, IL12p70, and IL10. As such, partner support during pregnancy that is both highly negative/upsetting and also highly positive/helpful predicted adaptive immunity markers in infants at 3 months of age.

Developmental origins of infant emotion regulation: Mediation by temperamental negativity and moderation by maternal sensitivity.

Emotion regulation is essential to cognitive, social, and emotional development and difficulties with emotion regulation portend future socioemotional, academic, and behavioral difficulties. There is growing awareness that many developmental outcomes previously thought to begin their development in the postnatal period have their origins in the prenatal period. Thus, there is a need to integrate evidence of prenatal influences within established postnatal factors, such as infant temperament and maternal sensitivity. In the current study, prenatal depression, pregnancy anxiety, and diurnal cortisol patterns (i.e., the cortisol awakening response (CAR) and diurnal slope) were assessed in 254 relatively low-risk mother-infant pairs (primarily White, middle-class) in early (M = 15 weeks) and late pregnancy (M = 33 weeks). Mothers reported on infant temperamental negativity (Infant Behavior Questionnaire-Revised) at 3 months. At 6 months, maternal sensitivity (Parent Child Interaction Teaching Scale) and infant emotion regulation behavior (Laboratory Temperament Assessment Battery) were assessed. Greater pregnancy anxiety in early pregnancy and a blunted CAR in late pregnancy predicted higher infant temperamental negativity at 3 months, and those infants with higher temperamental negativity used fewer attentional regulation strategies and more avoidance (i.e., escape behavior) at 6 months. Furthermore, this indirect effect was moderated by maternal sensitivity whereby infants with elevated negativity demonstrated maladaptive emotion regulation at below average levels of maternal sensitivity. These findings suggest that the development of infant emotion regulation is influenced by the ways that prenatal exposures shape infant temperament and is further modified by postnatal caregiving. (PsycINFO Database Record