Neural correlates of face familiarity in institutionalised children and links to attachment disordered behaviour.

BACKGROUND: One of the most well-documented sequelae of early maltreatment and institutionalisation is attachment problems, including behaviours under the labels of reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED). Despite growing evidence of the neurobiological effects of institutionalisation, the neural correlates of these behavioural patterns are largely unknown. METHODS: The current study examined effects of both institutionalisation in general and attachment disordered behaviour, in particular, on brain-based markers of face processing, in 100 Portuguese children (70 currently institutionalised, 30 continuously raised by their families). Children's neural processing of caregiver's and stranger's faces was assessed with Event-Related Potentials (ERPs). RESULTS: Compared to children from the community, institutionalised children showed smaller amplitudes in the N170, to both stranger and caregiver faces. Amongst the institutionalised group, living in a setting with a higher children-to-caregivers' ratio was associated with smaller P400 amplitudes. The display of DSED symptoms was associated with a smaller P1 to both faces, as well as a reduced differentiation between faces in P400 amplitudes and smaller P400 to the stranger's face. In contrast, RAD symptoms were not associated with any ERP measures. CONCLUSIONS: Results replicate previously reported hypoactivation in institutionalised children, in a less-globally deprived setting than past work, indicating that such a pattern is associated with lack of individualised care and increased symptoms of DSED.

Experiences, concerns, and needs of pregnant and postpartum women during the Covid-19 pandemic in Cyprus: a cross-sectional study.

BACKGROUND: The current COVID-19 pandemic is a unique stressor with potentially challenging and negative consequences on the experiences of pregnant and postpartum women. International literature highlights the pandemic's negative impact on women's perinatal experiences. This is the first study in the scientific literature reporting on the impact of the COVID-19 pandemic, on the perinatal experiences of a large sample of women living in Cyprus. AIM: To examine the impact of the COVID-19 pandemic on the experiences, concerns and needs of pregnant and postpartum women in Cyprus. METHOD: The cross-sectional study was conducted from July 2020 to January 2021. A total of 695 women, 355 pregnant and 340 postpartum women (with infants up to 6 months of age), residing in Cyprus were surveyed. RESULTS: The great majority of the participants (80.9%) perceived the impact of the COVID-19 pandemic on their life as negative. The greatest sources of stress were identified and quantified for their impact on the participants. Our findings indicate that 74.1% of the pregnant women were concerned about changes due to COVID-19 measures impacting the presence of their family at the time of delivery, 57.2% about their newborn's health, and 43.1% about changes related to perinatal care. Postpartum women's concerns were mainly related to the welfare and health of their child (70.3%), whilst half of them (49.1%) expressed concerns about how they were going to care for their baby because of pandemic-related changes. Qualitative data revealed emerging themes as the basis of the pregnant and postpartum women's concerns and needs. CONCLUSIONS: The COVID-19 pandemic and the associated imposed measures and restrictions had adverse effects on pregnant and postpartum women's perinatal experiences in Cyprus. The women's concerns emphasized the need for the development of specialized, evidenced-based support systems which are essential particularly in pandemic-like situations, when pregnant and postpartum women are more vulnerable to isolation.

Mothers' distress exposure and children's withdrawn behavior - A moderating role for the Interferon Gamma gene (IFNG).

The dysregulation of the inflammatory response, including pro-inflammatory molecules, produces neuropsychiatric symptoms and depression-like behavior, including withdrawal from the physical and social environment. Genetic variants that enhance immune reactivity may thus increase inflammatory and withdrawn reactions to stress. Here we investigated a functional polymorphism of Interferon Gamma gene (IFNG +874 T > A, rs2430561) as moderator of the relationship between mothers' distress exposure and children's withdrawn behavior at preschool age. Participants were 198 Portuguese preschool children (mean age = 57.98 months). Exposure to mother's distress was assessed using the Brief Symptom Inventory, and withdrawn behavior with the Caregiver Teacher Report Form. All children provided saliva samples for genotyping. Contrary to expecations based on prior work, the rs2430561 AA genotype-not the T variant-interacted with (high levels of) mothers' distress exposure, to increase children's withdrawn behavior. No significant main effects were detected. The polymorphism in Interferon Gamma gene showed specific environmental stressor-dependent effects on withdrawn behavior during childhood, ones which are interpreted in light of the "behavioral immune system" hypothesis, and which proved inconsistent with diathesis-stress thinking.

Neural Correlates of Face Familiarity in Institutionally Reared Children With Distinctive, Atypical Social Behavior.

Although the impact of early adverse experience on neural processing of face familiarity has been studied, research has not taken into account disordered child behavior. This work compared the neural processing of familiar versus strangers' faces in 47 institutionalized children with a mean age of 54 months to determine the effects of (a) the presence versus absence of atypical social behavior and (b) inhibited versus indiscriminant atypical behavior. Results revealed a pattern of cortical hypoactivation in institutionalized children manifesting atypical social behavior and that inhibited children displayed larger neural response to a caregiver's face than to the stranger's, while indiscriminant children did not discriminate between stimuli. These findings suggest that neural correlates of face familiarity are associated with social functioning in institutionalized children.

Cortisol reactivity and negative affect among preterm infants at 12 months during a mother-infant interaction task.

The purpose of this study was to investigate correlates of preterm (PT) infant's cortisol reactivity and the association to infant negative affect, during a mother-infant interaction procedure. Participants included 48 infants born prematurely (gestational age < 37 weeks) and their mothers, assessed when infants were 12 months old corrected for prematurity. The examined variables comprised both neonatal and environmental dimensions including maternal interactive behavior. Infant negative affect and maternal interactive behavior were assessed with a standardized mother-infant interaction task. A baseline infant saliva sample was collected before the interaction began, and a second sample after the interaction episodes ended. Results revealed that decrease of infant's cortisol concentration was significantly associated with the exposure to more sensitive, and less intrusive maternal behaviors. However, once controlled for neonatal risk, family SES and maternal psychological distress, the associations were rendered non-significant. Although the association between cortisol reactivity and negative affect trended toward significance, maternal intrusiveness was the only significant predictor of observed infant negative affect. Findings suggest the importance of primary relational experiences on PT infants' early regulatory competencies.

Non-invasive diagnosis and monitoring tool of children's mental health: A point-of-care immunosensor for IL-6 quantification in saliva samples.

Mental disorders are commonly featured as chronic conditions with often onset during childhood. In this context, inflammation has been associated with a higher risk of developing physical and mental health problems. Interleukin (IL)-6 is a key mediator of inflammatory responses and plays a pivotal role in immune and nervous system interaction. High levels of IL-6 during childhood are associated with mental problems, indicating that the IL-6 molecular pathway may represent a new target for monitoring and treating these conditions. Here, we report the detection of IL-6 in saliva samples from children (N = 118, mean age 4.4 years old) with behavioral problems using an immunosensor based on electrochemical impedance spectroscopy. This work demonstrates that the proposed immunosensor requires smaller sample volumes and is significantly faster and more sensitive than conventional ELISA while maintaining comparable levels of specificity and reproducibility. The point-of care immunosensor for detection of IL-6 in saliva samples presented herewith is, therefore, an attractive solution to the clinical practice as a rapid non-invasive, high-sensitive monitoring tool of mental health problems, especially in vulnerable patient populations such as children.

Maternal Interactive Behaviours in Parenting Children with Williams Syndrome and Autism Spectrum Disorder: Relations with Emotional/Behavioural Problems.

This study compared maternal responsiveness to children with two neurodevelopmental disorders sharing different but, in some cases, overlapping social phenotypes-Williams syndrome (WS) and autism spectrum disorder (ASD)-and explored the relations between maternal responsiveness and child emotional/behavioural problems (EBP). The sample included 16 pre-schoolers with WS and 43 with ASD, and their mothers. Responsiveness was assessed during a mother-child interaction task. Mothers completed the CBCL 1½-5, providing a measure of EBP. No significant differences emerged between groups, and most dyads were characterized by less responsive behaviours. Maternal responsiveness proved related to child developmental age, but not with EBP. These results provide further insight into the rearing environment of children with neurodevelopmental disorders, highlighting the need for early relationship-based interventions.

Child's oxytocin response to mother-child interaction: The contribution of child genetics and maternal behavior.

The oxytocinergic system is a primary biological system involved in regulating a child's needs for bonding and for protection from threats. It is responsive to social experiences in close relationships, though evidence across studies is not entirely consistent. Guided by previous literature, we investigated individual and environmental factors predicting and presumably affecting children's oxytocin (OT) response during mother-child interaction. by focusing on children's OXTR genotype, and maternal behavior, respectively. This was achieved by assessing salivary OT levels of 88 Portuguese preschoolers prior to and following a mother-child interaction task, and by genotyping children's OXTR SNP rs53576. Maternal interactive behavior was assessed using Ainsworth scales. Results indicated that child genotype and mother's sensitive responsiveness interacted in predicting change in child OT concentrations from before to after the interaction. Specifically, Genotypic differences emerged under conditions of low maternal sensitive responsiveness: OT levels increased over time for children with the GG genotype when maternal sensitive responsiveness was low, but no such genotypic differences were evident when mothers were highly sensitive responsive. Findings provide preliminary support for the notion that increased understanding of children's OT and close relationships requires consideration of both individual and environmental factors.

Gene-environment interactions in psychopathology throughout early childhood: a systematic review.

Up to 20% of children and adolescents worldwide suffer from mental health problems. Epidemiological studies have shown that some of these problems are already present at an early age. The recognition that psychopathology is a result of an interaction between individual experiences and genetic characteristics has led to an increase in the number of studies using a gene-environment approach (G×E). However, to date, there has been no systematic review of G×E studies on psychopathology in the first 6 years of life. Following a literature search and a selection process, 14 studies were identified and most (n=12) of the studies found at least one significant G×E effect. This review provides a systematic characterization of the published G×E studies, providing insights into the neurobiological and environmental determinants involved in the etiology of children's psychopathology.

Role of human umbilical cord mesenchymal progenitors conditioned media in neuronal/glial cell densities, viability, and proliferation.

It has been recently reported that mesenchymal progenitor/stem cells isolated from the Wharton's Jelly (WJ) of umbilical cords (UC) ameliorate the condition of animals suffering from central nervous system (CNS)-related conditions. However, little is known on the mechanisms that regulate these actions. Therefore, the objective of the present work was to determine how the conditioned media (CM) of a population of mesenchymal progenitors present in the UC WJ, known as human umbilical cord perivascular cells (HUCPVCs), regulate processes such as cell viability, survival, and proliferation of postnatal hippocampal neurons and glial cells. For this purpose primary hippocampal and cortical cultures of neurons and glial cells, respectively, were incubated with CM from HUCPVCs. Results revealed that HUCPVCs CM increase glial cell viability and proliferation. Furthermore, it was observed that glial cell cultures exhibited higher numbers of GFAP-positive cells (astrocytes) and O4-positive cells (oligodendrocytes) when incubated with the CM. Additionally, it was also observed that the growth factors presents in the CM did not induce an increase on the microglial cells number. For hippocampal neurons similar results were obtained, as cultures exposed to HUCPVCs CM disclosed higher numbers of MAP-2-positive cells. Moreover it was also observed that the cell viability and proliferation in this primary hippocampal cell culture system was also higher, when compared to control cultures. From these results it was possible to conclude that HUCPVCs release neuroregulatory factors that have a direct impact on the densities, viability, and proliferation of glial cells and hippocampal primary cultures.

A trans-dimensional approach to the behavioral aspects of depression.

Depression, a complex mood disorder, displays high comorbidity with anxiety and cognitive disorders. To establish the extent of inter-dependence between these behavioral domains, we here undertook a systematic analysis to establish interactions between mood [assessed with the forced-swimming (FST) and sucrose consumption tests (SCT)], anxiety [elevated-plus maze (EPM) and novelty suppressed feeding (NSF) tests] and cognition (spatial memory and behavioral flexibility tests) in rats exposed to unpredictable chronic-mild-stress (uCMS). Expectedly, uCMS induced depressive-like behavior, a hyperanxious phenotype and cognitive impairment; with the exception of the measure of anxiety in the EPM, these effects were attenuated by antidepressants (imipramine, fluoxetine). Measures of mood by the FST and SCT were strongly correlated, whereas no significant correlations were found between the different measures of anxiety (EPM and NSF); likewise, measures of cognition by spatial memory and behavioral flexibility tests were poorly correlated. Inter-domain analysis revealed significant correlations between mood (FST and SCT) and anxiety-like behavior (NSF, but not EPM). Furthermore, significant correlations were found between cognitive performance (reverse learning task) and mood (FST and SCT) and anxiety-like behavior (NSF). These results demonstrate interactions between different behavioral domains that crosscut the disciplines of psychiatry and neurology.

Chronic stress causes frontostriatal reorganization and affects decision-making.

The ability to shift between different behavioral strategies is necessary for appropriate decision-making. Here, we show that chronic stress biases decision-making strategies, affecting the ability of stressed animals to perform actions on the basis of their consequences. Using two different operant tasks, we revealed that, in making choices, rats subjected to chronic stress became insensitive to changes in outcome value and resistant to changes in action-outcome contingency. Furthermore, chronic stress caused opposing structural changes in the associative and sensorimotor corticostriatal circuits underlying these different behavioral strategies, with atrophy of medial prefrontal cortex and the associative striatum and hypertrophy of the sensorimotor striatum. These data suggest that the relative advantage of circuits coursing through sensorimotor striatum observed after chronic stress leads to a bias in behavioral strategies toward habit.

Increased expression of ferritin, an iron-storage protein, in specific regions of the parahippocampal cortex of epileptic rats.

PURPOSE: Iron accumulation in the brain has been associated with neurodegenerative disorders, including epilepsy. In our previous SAGE study, we showed that ferritin, an iron-storage protein, was one of the genes (Ferritin-H) that showed overexpression before the chronic epileptic phase. In this study we used ferritin as indicator for disturbed iron homeostasis to acquire insight into whether this could play a role in the pathogenesis of temporal lobe epilepsy. METHODS: With immunocytochemistry, we studied the regional and cellular distribution of ferritin protein in an animal model for temporal lobe epilepsy in which spontaneous seizures develop a few weeks after electrically induced status epilepticus (SE). RESULTS: Increased ferritin expression was observed in regions known to be vulnerable to cell death, mainly in reactive microglial cells of epileptic rats. Ferritin expression after SE was initially high, especially throughout the hippocampus, but decreased over time. In the chronic epileptic phase, it was still upregulated in regions where extensive cell loss occurs during the early acute and latent period. Within the parahippocampal region, the most persistent ferritin overexpression was present in microglial cells in layer III of the medial entorhinal area. The upregulation was most extensive in rats that had developed a progressive form of epilepsy with frequent seizures (approximately five to 10 seizures per day). CONCLUSIONS: The fact that ferritin upregulation is still present in specific limbic regions in chronic epileptic rats, when neuronal loss is absent or minimal, suggests a role of iron in the pathogenesis and progression of epilepsy.