A multi-systems approach to understanding the effects of antenatal distress: biological underpinnings of perinatal depressive symptoms and biobehavioural outcomes in the child

Evidence linking maternal antenatal depression with an increased risk of altered biological and behavioral outcomes in offspring is substantial. However, knowledge concerning the underlying mechanisms is strikingly less advanced. The current dissertation addresses this gap by adopting a multi-systems approach and prospectively investigating three main biological pathways, involving stress and inflammation, possibly underlying the effects of maternal antenatal depression on infants’ early development, taking into account the potential buffering role of postnatal maternal care. One-hundred-ten healthy pregnant women, together with their offspring, were studied from late pregnancy to three months after delivery as part of the Effects of Depression on Infants (EDI) Study. In Chapter 3, cross-sectional associations between maternal depressive symptoms and stress-related biology in late pregnancy and soon after delivery were examined. Chapters 4 and 5 investigated the prospective associations between antenatal variations in maternal depressive symptoms, stress and inflammation and infant behavioral and biological outcomes at birth (Chapter 4) and 3 months after delivery (Chapter 5). Lastly, Chapter 6 explored the moderating role of maternal caregiving in the association between prenatal maternal influences and 3- month-olds’ bio-behavioral outcomes. Current findings indicate that antenatal depressive symptoms are associated with an altered diurnal cortisol pattern and heightened inflammation in late pregnancy and independently predict 3-month-olds’ negative affectivity. Additionally, this thesis provides evidence that variations in maternal stress-related biology during pregnancy are associated with offspring physiological and behavioural outcomes and that the impact of antenatal maternal cortisol on infant cortisol stress reactivity may be moderated by maternal sensitive caregiving. Despite the fact that replication of these findings in larger and different samples is needed, our results are in keeping with the hypothesis that maternal antenatal stress exerts a programming effect on offspring bio-behavioral development and that the impact partially depends on the quality of the early rearing environment

Emotional Availability in Samples of Mothers at High Risk for Depression and With Substance Use Disorder

Background: Maternal substance use disorder (SUD) and depression have been extensively associated with dysfunctions in parent-child interactions. However, few studies have compared caregiving behaviors of these mothers. The current study aims to explore maternal emotional availability (EA) in mothers with maternal SUD and depressive symptoms in order to investigate whether these conditions represent a different risk gradient for early parenting.Methods: Mother-infant relationship was investigated in 18 mothers with SUD, 11 mothers at risk for depression, and 39 mothers from general population. The dyads were videotaped during a free-play session and the quality of parent-child interactions was assessed using the EA Scales (EAS) and the Emotional Attachment and EA Clinical Screener (EA2-CS).Results: Mothers with SUD scored lower on sensitivity, non-intrusiveness, and non-hostility with respect to the low-risk sample, whereas mothers at risk for depression scored lower on sensitivity and non-hostility compared to the latter. No significant differences between mothers with SUD and mothers at risk for depression emerged on the EAS, whereas different specific classifications on the EA Clinical Screener were found for the SUD (i.e., Complicated), depression (i.e., Detached), and low-risk (i.e., Emotionally Available) samples.Conclusion: If the current findings are replicated, they might have significant implications for selecting targets of early mother-infant interventions

Maternal caregiving moderates the impact of antenatal maternal cortisol on infant stress regulation

Background Emerging evidence suggests that antenatal exposure to maternal stress signals affects the development of the infant stress response systems. Animal studies indicate that maternal sensitive caregiving can reverse some of these effects. However, the generalizability of these findings to humans is unknown. This study investigated the role of maternal caregiving in the association between multiple markers of maternal antenatal stress and infant stress regulation. Methods The sample consisted of 94 mother-infant (N = 47 males, mean postnatal weeks = 12; SD = 1.84) dyads. Maternal levels of Interleukin-6, C-Reactive Protein (CRP), diurnal cortisol and alpha amylase, depressive and anxiety symptoms were assessed in late pregnancy (mean gestational age = 34.76; SD = 1.12), whereas postnatal symptomatology, caregiving, and infant cortisol response to the inoculation were evaluated at 3 months. Results Hierarchical linear models (HLMs) showed a significant interaction between maternal antenatal cortisol, caregiving, and time on infant cortisol reactivity, while controlling for gender, maternal age, and postnatal depression. Specifically, higher levels of maternal antenatal cortisol were associated with greater cortisol response only among infants of less emotionally available mothers. All other markers of antenatal stress were not significantly associated with infant cortisol reactivity either independently or in interaction with maternal caregiving. Conclusions Albeit preliminary, results provide the first evidence in humans that maternal sensitive caregiving may eliminate the association between antenatal maternal cortisol and infant cortisol regulation

Neuroendocrine and immune markers of maternal stress during pregnancy and infant cognitive development

Antenatal exposure to maternal stress is a factor that may impact on offspring cognitive development. While some evidence exists of an association between maternal antenatal depressive or anxiety symptoms and infants’ cognitive outcomes, less is known about the role of biological indices of maternal antenatal stress in relation to infant cognitive development. The current study investigated the association between maternal depressive and anxiety symptoms, stress and inflammatory markers during pregnancy and infant’s cognitive development in a sample of 104 healthy pregnant women (mean gestational age=34.76; SD=1.12) and their 12-week-old infants (mean postnatal weeks=11.96; SD=1.85). Maternal depressive and anxiety symptoms were evaluated during pregnancy, alongside measurements of serum Interleukin-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol and alpha amylase (sAA) concentrations. Infant cognitive development, maternal caregiving and concurrent anxiety or depressive symptoms were assessed 12 weeks after delivery. Hierarchical linear regressions indicated that higher maternal diurnal cortisol and CRP levels were independently associated with lower infant cognitive development scores, while adjusting for infant gender and gestational age, maternal IQ, caregiving, depressive or anxiety symptoms. Though correlational, findings seem suggestive of a role for variation in maternal biological stress signals during pregnancy in influencing infants’ early cognitive development

Kinetic partitioning of major-minor cations between olivine and Hawaiian tholeiitic basalt under variable undercooling and cooling rate conditions

In order to elucidate the kinetic partitioning of cations between olivine and basalt, we performed undercooling (−ΔT) and cooling rate (CR) experiments at atmospheric pressure and QFM-2 buffer. Starting from the super- liquidus temperature of 1250 ◦C, a Hawaiian tholeiitic basalt was cooled at the rates of 4 (CR4), 20 (CR20), and 60 (CR60) ◦C/h to the final target temperatures of 1175 ◦C (−ΔT = 35 ◦C; −ΔT35) and 1125 ◦C (−ΔT = 85 ◦C; −ΔT85). Results show that polyhedral olivine morphologies are obtained at -ΔT35, whereas strong disequilib- rium skeletal and/or dendritic textures form at -ΔT85. The amount of forsterite in olivine decreases from to 85% to 78% with increasing both -ΔT and CR. A diffusive boundary layer also develops in the melt next to the olivine surface and its composition becomes progressively enriched in Ca, owing to its incompatible behavior with the lattice site. Residual melts are progressively depleted in silica and enriched in alkali from CR4 to CR60, but silica- rich melts are observed with increasing -ΔT. In terms of Fe2+-Mg exchange, olivines obtained at -ΔT35 are always in equilibrium with the diffusive boundary layer, comprising both the interface melt next to the olivine surface and the far-field melt where all chemical gradients cease. At -ΔT85, however, the Fe2+-Mg exchange indicates two distinct equilibration stages between olivine core and far-field melt, and between olivine rim and interface melt. Partition coefficients (Kd) of Mg, Fe, Mn, Ca, and Cr calculated at the olivine-melt interface preferentially change as a function of -ΔT rather than CR. From -ΔT35 to -ΔT85, KdMg, KdFe, KdMn, and KdCr remarkably in- crease, whereas the opposite applies to KdCa. Through the application of equilibrium partitioning models, we found that Mg, Fe, Mn, and Ca are incorporated into the olivine lattice site at near-equilibrium proportions. This generally good agreement with modeling data demonstrates that diffusive mass transport of cations in our ex- periments occurred under the conditions of local equilibrium at the olivine surface. In contrast, marked de- viations from the expected equilibrium are found for KCr in response to the major influence of crystal field stabilization energy on cation incorporation

Kinetic aspects of major and minor elements in olivine from variably cooled basaltic melts

Olivine is an important mineral phase in naturally cooled basaltic rocks. The texture and composition of olivine are strictly related to the interplay between the degree of magma undercooling and crystal growth rate. Crystals formed at low undercoolings and growth rates generally show polyhedral-hopper textures and quite homogeneous compositions, while skeletal-dendritic textures and strong crystal zonation occur at high undercoolings and growth rates. In this context, we have performed disequilibrium crystallization experiments to better understand the effects of crystallization kinetics on the incorporation of major and minor cations in the olivine lattice. Experiments were carried out in a 1 atm vertical tube CO-CO2 gas-mixing furnace using basaltic glass (i.e., OIB) as starting material, imposing different undercooling and cooling rates. We used room pressure and QFM-2 oxygen fugacity. Each experiment started at superliquidus temperature, which was kept constant for 2 h before cooling. After this stage, we linearly decreased the temperature to the final target of 1125 and 1175 °C, for a total undercooling (-ΔT) of 85 °C and 35 °C, respectively. Each experiment was tested at different cooling rates: 2 °C/h, 20 °C/h, and 60 °C/h. Finally, samples were quenched for recovery. Results show that the olivine texture shifts from euhedral (i.e. polyhedral texture) to anhedral (i.e. dendritic texture) as function of the undercooling during rapid crystal growth. In -ΔT = 35 °C experiments, olivine crystals show a faint zonation. Conversely, a strong zonation develops in crystals grown during - ΔT = 85 °C. The compositional gradient in the melt increases with increasing cooling rate and undercooling, forming a diffusive boundary layer that expands towards the far field melt (15 μm wide for low undercooling and minimum 2 time wider for high undercooling). Because of the effects of crystallization kinetics, skeletal-dendritic olivine incorporates higher proportions of minor elements, which are generally incompatible within the crystal lattice at equilibrium conditions. Al, P, Ti and Cr distribution seem to follow the primary and secondary olivine branches

Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: When timing matters

This database includes the raw data linked with the paper “Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: When timing matters” published on Translational Psychiatry, doi: 10.1038/s41398-022-02160-0. This publication is part of the longitudinal and multi-centric “Measuring the outcomes of maternal COVID-19-related prenatal exposure (MOM-COPE)” research project. In this paper, we report data on NR3C1 and SLC6A4 methylation status in Italian mothers and infants who were exposed to the COVID-19 pandemic lockdown during different trimesters of pregnancy. Procedures: 283 mother-infant dyads were enrolled at delivery. Within 24 hours from delivery, buccal cells were collected to assess NR3C1 (44 CpG sites) and SLC6A4 (13 CpG sites) methylation status. Mothers self-reported on depressive symptoms and anxiety by replying to an online adapted version of the well-validated Beck Depression Inventory and State-Trait Anxiety questionnaires, respectively. Analytical plan: Principal component (PC) analyses were used to reduce methylation data dimension to one PC per maternal and infant gene methylation. Mother-infant dyads were split into three groups based on the pregnancy trimester during which they were exposed to the COVID-19 lockdown. To assess the presence of significant differences in maternal and infant methylation of SLC6A4 and NR3C1 genes by pregnancy trimester of exposure to the COVID-19 pandemic lockdown, four separate one-way ANOVAs were carried out with Trimester (levels: third, second, first) as the between-subject variable and each of the methylation PCs. Findings in brief: Mothers and infants who were exposed to the lockdown during the first trimester of pregnancy had lower NR3C1 and SLC6A4 methylation when compared to counterparts exposed during the second or third trimesters. The effect remained significant after controlling for confounders

Kinetic aspects of major and minor elements in olivine from variably cooled basaltic melts

Olivine is an important mineral phase in naturally cooled basaltic rocks. The texture and composition of olivine are strictly related to the interplay between the degree of magma undercooling and crystal growth rate. Crystals formed at low undercoolings and growth rates generally show polyhedral-hopper textures and quite homogeneous compositions, while skeletal-dendritic textures and evident crystal zonations occur at high undercoolings and growth rates. In this context, we have performed equilibrium and disequilibrium (i.e., cooling rate) experiments to better understand, by a comparatively approach, the effects of crystallization kinetics on the incorporation of major and trace cations in olivine lattice. The experiments were carried out in a 1 atm vertical tube CO-CO2 gas-mixing furnace to perform experiment at atmospheric pressure and oxygen fugacity of QFM-2 using a basaltic glass (i.e., OIB) as starting materials. The equilibrium experiment was performed at 1175 °C. These target temperatures were kept constant for 240 h and then quenched. Conversely, the disequilibrium experiments were performed at the superliquidus temperature of 1250, and 1300 °C, which was kept constant for 2 h before cooling. The final target temperatures of 1150 (undercooling -ΔT = 50 °C), and 1175 °C (-ΔT = 25 °C) were attained by applying cooling rates of 2 °C/h, 20 °C/h, and 60 °C/h. Then the experimental charges were quenched. Results show that the olivine texture shifts from euhedral (i.e., equilibrium) to anhedral (i.e., disequilibrium) under the effect of cooling rate and rapid crystal growth. In equilibrium experiments, the composition of olivine is homogeneous and non chemical gradients are found in the melt next to the crystal surface. In contrast, a diffusive boundary layer develops in the melt surrounding the olivine crystals growing rapidly under the effect of cooling rate and degree of undercooling. The compositional gradient in the melt increases with increasing cooling rate and undercooling, causing the diffusive boundary layer to expand towards the far field melt (15 μm wide for low undercooling and 2 time wider for high undercooling). Because of the effects of crystallization kinetics, skeletal-dendritic olivines incorporates higher proportions of major and trace elements that are generally incompatible within their crystal lattice under equilibrium conditions

Respiratory Sinus Aarrhythmia (RSA) stress response in preschool age varies by serotonin transporter polymorphism (5-HTTLPR): A preliminary report

The serotonin transporter promoter region polymorphism (5-HTTLPR) has been implicated in stress regulation, with increased stress reactivity often being found in carriers of the low-expressing short (S) allele. Nevertheless, the role of the 5-HTTLPR in influencing parasympathetic stress reactivity, as indexed by Respiratory Sinus Arrhythmia (RSA), is still unknown. This study examined, for the first time, whether the 5-HTTLPR was associated with variations in RSA response to maternal separation in a sample of 69 healthy 5-year-old children. Preschoolers’ RSA was measured during an age-adapted version of the Strange Situation Procedure (SSP). The 5-HTTLPR polymorphism was tested as a predictor of RSA dynamic response to the SSP through multilevel models. A significant interaction between 5-HTTLPR and SSP episodes was found. In particular, whereas a significant decrease in RSA levels was observed during the stranger episode in the whole sample, S allele carriers showed a significant decrease in RSA levels from the stranger episode to the first separation episode, followed by an increase for the rest of the procedure. Albeit preliminary, data support the view that the 5-HTTLPR may contribute to individual differences in RSA stress reactivity from preschool age