The effects of parental presence on amygdala and mPFC activation during fear conditioning: An exploratory study.

Learning safe versus dangerous cues is crucial for survival. During development, parents can influence fear learning by buffering their children's stress response and increasing exploration of potentially aversive stimuli. Rodent findings suggest that these behavioral effects are mediated through parental presence modulation of the amygdala and medial prefrontal cortex (mPFC). Here, we investigated whether similar parental modulation of amygdala and mPFC during fear learning occurs in humans. Using a within-subjects design, behavioral (final N = 48, 6-17 years, mean = 11.61, SD = 2.84, 60% females/40% males) and neuroimaging data (final N = 39, 6-17 years, mean = 12.03, SD = 2.98, 59% females/41% males) were acquired during a classical fear conditioning task, which included a CS+ followed by an aversive noise (US; 75% reinforcement rate) and a CS-. Conditioning occurred once in physical contact with the participant's parent and once alone (order counterbalanced). Region of interest analyses examined the unconditioned stress response by BOLD activation to the US (vs. implicit baseline) and learning by activation to the CS+ (vs. CS-). Results showed that during US presentation, parental presence reduced the centromedial amygdala activity, suggesting buffering of the unconditioned stress response. In response to learned stimuli, parental presence reduced mPFC activity to the CS+ (relative to the CS-), although this result did not survive multiple comparisons' correction. These preliminary findings indicate that parents modulate amygdala and mPFC activity during exposure to unconditioned and conditioned fear stimuli, potentially providing insight into the neural mechanisms by which parents act as a social buffer during fear learning. RESEARCH HIGHLIGHTS: (1)This study used a within-participant experimental design to investigate how parental presence (vs. absence) affects youth's neural responses in a classical fear conditioning task. (2)Parental presence reduced the youth's centromedial amygdala activation to the unconditioned stimulus (US), suggesting parental buffering of the neural unconditioned response (UR). (3)Parental presence reduced the youth's mPFC activation to a conditioned threat cue (CS+) compared to a safety cue (CS-), suggesting possible parental modulation of fear learning.

Childhood adversity is associated with anxiety and depression in older adults: A cumulative risk and latent class analysis.

BACKGROUND: The long-lasting influence of childhood adversity on mental health is well documented; however empirical research examining how this association extends into older adults is limited. This study operationalises adversity using cumulative risk and latent class analysis (LCA) models to assess how adversity exposure and typologies may predict anxiety and depression in older adults. METHODS: Data came from the Personality and Total Health (PATH) Through Life Project (N = 2551, age 60-66). Participants retrospectively reported their childhood experiences of domestic adversity on a 17-item scale. Mental health was measured using four validated questionnaires of depression and anxiety. RESULTS: Linear and generalised additive models (GAM) indicated a dose-response relationship, where a greater number of cumulative adversities were associated with poorer scores on all four mental health measures. LCA identified a four-class solution; with high adversity and high parental dysfunction being associated with poorer mental health outcomes while moderate parental dysfunction and low adversity groups scored at healthy levels. Women reported higher overall anxiety than men, but no notable interactions between ACEs and gender were observed. Patterns revealed by LCA were similar to patterns shown by the cumulative risk model. LIMITATIONS: There is a large time gap from childhood to assessment, making our study susceptible to recall bias. Also, our findings were based on cross-sectional data, limiting causal inferences. CONCLUSION: Childhood adversity had independent and additive contributions to depression and anxiety in older adulthood, and both cumulative risk and person-centred approaches captured this relationship.

Neuroimaging and Neurodevelopmental Outcomes Among Individuals With Complex Congenital Heart Disease: JACC State-of-the-Art Review.

Although neuroimaging advances have deepened our understanding of brain health in individuals with congenital heart disease (CHD), it is less clear how neuroimaging findings relate to neurodevelopmental and mental health outcomes across the lifespan. We systematically synthesized and critically evaluated evidence on associations between neuroimaging and neurodevelopmental, neurocognitive, psychiatric, or behavioral outcomes among individuals with transposition of great arteries or single-ventricle CHD (Protocol CRD42021229617). Six databases were searched and 45 papers from 25 unique studies were identified. Structural brain injury was generally linked to poorer neurodevelopment in infancy. Brain volumes and microstructural and functional brain changes appear linked to neurocognitive outcomes, including deficits in attention, learning, memory, and executive function in children and adolescents. Fetal neuroimaging studies were limited. Four papers investigated psychiatric outcomes; none found associations with neuroimaging. Multicenter, longitudinal studies incorporating functional neuroimaging and mental health outcomes are much-needed to inform early neuroprotective and therapeutic strategies in CHD.

A comparison of the infant gut microbiome before versus after the start of the covid-19 pandemic.

The COVID-19 pandemic and resulting public health directives led to many changes in families' social and material environments. Prior research suggests that these changes are likely to impact composition of the gut microbiome, particularly during early childhood when the gut microbiome is developing most rapidly. Importantly, disruption to the gut microbiome during this sensitive period can have potentially long-lasting impacts on health and development. In the current study, we compare gut microbiome composition among a socioeconomically and racially diverse group of 12-month old infants living in New York City who provided stool samples before the pandemic (N = 34) to a group who provided samples during the first 9-months of the pandemic (March-December 2020; N = 20). We found that infants sampled during the pandemic had lower alpha diversity of the microbiome, lower abundance of Pasteurellaceae and Haemophilus, and significantly different beta diversity based on unweighted Unifrac distance than infants sampled before the pandemic. Exploratory analyses suggest that gut microbiome changes due to the pandemic occurred relatively quickly after the start of the pandemic and were sustained. Our results provide evidence that pandemic-related environmental disruptions had an impact on community-level taxonomic diversity of the developing gut microbiome, as well as abundance of specific members of the gut bacterial community.

Multigenerational adversity impacts on human gut microbiome composition and socioemotional functioning in early childhood.

Adversity exposures in the prenatal and postnatal period are associated with an increased risk for psychopathology, which can be perpetuated across generations. Nonhuman animal research highlights the gut microbiome as a putative biological mechanism underlying such generational risks. In a sample of 450 mother-child dyads living in Singapore, we examined associations between three distinct adversity exposures experienced across two generations-maternal childhood maltreatment, maternal prenatal anxiety, and second-generation children's exposure to stressful life events-and the gut microbiome composition of second-generation children at 2 y of age. We found distinct differences in gut microbiome profiles linked to each adversity exposure, as well as some nonaffected microbiome features (e.g., beta diversity). Remarkably, some of the microbial taxa associated with concurrent and prospective child socioemotional functioning shared overlapping putative functions with those affected by adversity, suggesting that the intergenerational transmission of adversity may have a lasting impact on children's mental health via alterations to gut microbiome functions. Our findings open up a new avenue of research into the underlying mechanisms of intergenerational transmission of mental health risks and the potential of the gut microbiome as a target for intervention.

The Added Value of Crosstalk Between Developmental Circuit Neuroscience and Clinical Practice to Inform the Treatment of Adolescent Anxiety.

Significant advances have been made in recent years regarding the developmental trajectories of brain circuits and networks, revealing links between brain structure and function. Emerging evidence highlights the importance of developmental trajectories in determining early psychiatric outcomes. However, efforts to encourage crosstalk between basic developmental neuroscience and clinical practice are limited. Here, we focus on the potential advantage of considering features of neural circuit development when optimizing treatments for adolescent patient populations. Drawing on characteristics of adolescent neurodevelopment, we highlight two examples, safety cues and incentives, that leverage insights from neural circuit development and may have great promise for augmenting existing behavioral treatments for anxiety disorders during adolescence. This commentary seeks to serve as a framework to maximize the translational potential of basic research in developmental populations for strengthening psychiatric treatments. In turn, input from clinical practice including the identification of age-specific clinically relevant phenotypes will continue to guide future basic research in the same neural circuits to better reflect clinical practices. Encouraging reciprocal communication to bridge the gap between basic developmental neuroscience research and clinical implementation is an important step toward advancing both research and practice in this domain.

It's Time to Rebrand "Mommy Brain".

This Viewpoint discusses the concept of "mommy brain" and why it needs to change.

Associations between the human immune system and gut microbiome with neurodevelopment in the first 5 years of life: A systematic scoping review.

The aim of this review was to map the literature assessing associations between maternal or infant immune or gut microbiome biomarkers and child neurodevelopmental outcomes within the first 5 years of life. We conducted a PRISMA-ScR compliant review of peer-reviewed, English-language journal articles. Studies reporting gut microbiome or immune system biomarkers and child neurodevelopmental outcomes prior to 5 years were eligible. Sixty-nine of 23,495 retrieved studies were included. Of these, 18 reported on the maternal immune system, 40 on the infant immune system, and 13 on the infant gut microbiome. No studies examined the maternal microbiome, and only one study examined biomarkers from both the immune system and the gut microbiome. Additionally, only one study included both maternal and infant biomarkers. Neurodevelopmental outcomes were assessed from 6 days to 5 years. Associations between biomarkers and neurodevelopmental outcomes were largely nonsignificant and small in effect size. While the immune system and gut microbiome are thought to have interactive impacts on the developing brain, there remains a paucity of published studies that report biomarkers from both systems and associations with child development outcomes. Heterogeneity of research designs and methodologies may also contribute to inconsistent findings. Future studies should integrate data across biological systems to generate novel insights into the biological underpinnings of early development.

Effects of maternal childhood trauma on child emotional health: maternal mental health and frontoamygdala pathways.

BACKGROUND: Experiences of early life adversity pose significant psychological and physical health risks to exposed individuals. Emerging evidence suggests that these health risks can be transmitted across generations; however, the mechanisms underlying the intergenerational impacts of maternal early-life trauma on child health remain unknown. METHODS: The current study used a prospective longitudinal design to determine the unique and joint contributions of maternal childhood trauma (neglect and abuse) and maternal prenatal and postnatal mental health (anxiety and depressive symptoms) (N = 541) to children's resting frontoamygdala functional connectivity at 6 years (N = 89) and emotional health at 7-8 years, as indexed by parent-reported internalizing problems and child self-reported anxiety and depressive symptoms (N = 268-418). RESULTS: Greater maternal childhood neglect was indirectly associated with greater internalizing problems serially through a pathway of worse maternal prenatal and postnatal mental health (greater maternal anxiety and depressive symptoms). Worse maternal postnatal mental health was also uniquely associated with more negative child frontoamygdala resting-state functional connectivity, over and above maternal childhood trauma (both neglect and abuse) and prenatal mental health. More negative frontoamygdala functional connectivity was, in turn, associated with poorer child emotional health outcomes. CONCLUSIONS: Findings from the current study provide support for the existence of intergenerational influences of parental exposure to childhood trauma on childhood risk for psychopathology in the next generation and point to the importance of maternal factors proximal to the second generation (maternal prenatal and postnatal mental health) in determining the intergenerational impact of maternal early experiences.

Sometimes "we" can help: parents' pronoun use buffers fear and anxiety transmission.

BACKGROUND AND OBJECTIVES: Parents' natural language when describing health-related threats reflects parents' cognitions that may shape their transmission of anxiety and fear. Parents' greater communal focus (i.e., higher we-talk) and less self-focus (i.e., lower I-talk) may buffer against intergenerational fear/anxiety transmission. The current study investigated whether the relation between parents' and children's anxiety and pandemic-related fear differed by parent we- and I-talk. DESIGN AND METHODS: Parents of 114 children (2-19 years; M = 9.75, SD = 3.73) completed online measures assessing children's and parents' anxiety and COVID-19-related fears, and engaged in a written reflection on their early pandemic experiences. The proportion of parents' we-talk and I-talk during the reflection was obtained using Linguistic Inquiry Word Count software. RESULTS: Results of multilevel structural equation models were partially consistent with expectations: The protective effect of we-talk was only observed for parents with lower fear/anxiety. For parents with higher fear/anxiety, higher I-talk was associated with lower child fear/anxiety. At higher levels of parent we-talk and at lower levels of I-talk, there was an unexpectedly positive association between parents' and children's fear/anxiety. CONCLUSIONS: The concordance between parents' and their children's fear/anxiety differs depending on parents' natural language when reflecting on the pandemic.

Virtual social interaction and loneliness among emerging adults amid the COVID-19 pandemic.

Many social activities moved online during the global COVID-19 pandemic, yet research investigating whether virtual social interactions facilitate social connectedness has been inconclusive. In this study, participants completed online questionnaires assessing objective social isolation, loneliness, mental health, and virtual social interactions. There was clear evidence for worsening mental health among emerging adults during the COVID-19 pandemic characterized by large increases in depressive symptoms (mean increase = 8.35, 95% CI [6.97, 9.73], t(118) = 118, p < .001), and large decrements in happiness (mean decrease = -0.71, 95% CI [-0.84, -0.57], t(118) = 10.09, p < .001) and social satisfaction (mean decrease = -0.81, 95% CI [-1.00,-0.62], t(115) = 8.28, p < .001) post-pandemic onset. In line with expectations, those living in larger households amid the pandemic reported lower levels of loneliness and higher levels of happiness. A negative association was found between household size (an index of objective social isolation) and loneliness, b = -3.01, t(79) = 2.60, p = .011, 95% CI [-5.32, -0.71], and a positive association was found between household size and happiness, b = 22.86, t(75) = 3.30, p = .001, 95% CI [9.06, 36.65]. However, contrary to expectations, there was no association between loneliness and frequency of virtual social interactions. There was also no association between frequency of virtual social interactions and either happiness or depression. More research investigating social connectedness in the context of virtual social interactions is warranted.

Fear modulates parental orienting during childhood and adolescence.

Adults quickly orient toward sources of danger and deploy fight-or-flight tactics to manage threatening situations. In contrast, infants who cannot implement the safety strategies available to adults and depend heavily on caregivers for survival are more likely to turn toward familiar adults, such as their parents, to help them navigate threatening circumstances. However, work has yet to investigate how readily children and adolescents orient toward their parents in threatening or fearful contexts. The current work addressed this question using a visual search paradigm that included arrays of parents' and strangers' faces as target and distractor stimuli, preceded by a fear or neutral emotional priming procedure. Linear mixed-effects models showed that children and adolescents (N = 88, age range = 4-17 years; 42M/46F) were faster to search for the face of their parent than of a stranger. However, fear priming attenuated this effect of the parent on search times, such that children and adolescents were significantly slower to orient toward their parent in an array of strangers' faces if they were first primed with fear as opposed to a neutral video. This work indicates that fear priming may phasically interfere with parental orienting during childhood and adolescence, possibly because fear reallocates attention away from parents and toward (potentially threatening) unfamiliar people in the environment to facilitate the development of independent threat learning and coping systems.

Parenting under pressure: Parental transmission and buffering of child fear during the COVID-19 pandemic.

The current study investigated the impacts of parental behaviors (threat communication and comforting) on children's COVID-19 fears and whether effects differed by age. Caregivers of 283 children (5.5-17 years, M = 10.17, SD = 3.25) from 186 families completed online measures assessing children's and parents' COVID-19-related fears, children's sources of COVID-19 threat information, and parents' engagement in behaviors to reduce child distress (i.e., comfort behaviors). Higher COVID-19 fear in parents was associated with greater communication of COVID-19 threat information, which was associated with higher COVID-19 fear in younger, but not older, children. Over and above parental fear and threat communication, greater exposure to COVID-19 threat information from community sources (e.g., media, school, friends) was associated with greater COVID-19 fear in children, regardless of age. Greater engagement of parental comfort behaviors buffered the association between community sources of COVID-19 threat information and COVID-19 fears in older, but not younger, children. These findings suggest that younger children might be more vulnerable to developing heightened COVID-19 fears as a result of increasing sources of COVID-19 threat information in their lives. This study highlights the importance of supporting the socioemotional well-being of children and families through the COVID-19 pandemic and beyond.

Being the third wheel: Toddlers use bystander learning to acquire cue-specific valence knowledge.

Observing others is an important means of gathering information by proxy regarding safety and danger, a form of learning that is available as early as infancy. In two experiments, we examined the specificity and retention of emotional eavesdropping (i.e., bystander learning) on cue-specific discriminant learning during toddlerhood. After witnessing one adult admonish another for playing with Toy A (with no admonishment for Toy B), toddlers learned to choose Toy B for themselves regardless of whether they were tested immediately or 2 weeks later (Experiment 1). However, if asked to make a toy choice for someone else (i.e., when toddlers' personal risk was lower), approximately half the toddlers instead selected Toy A (Experiment 2). However, such choices were accompanied by toddlers' social monitoring of the adults, suggesting that toddlers may have been attempting to safely gain (via surrogacy) more information about risk contingencies. These findings suggest that toddlers can learn to discriminate valence in a cue-specific manner through social observation.

Evidence for cognitive plasticity during pregnancy via enhanced learning and memory.

Human and animal neuroscience studies support the view that plastic shifts occur in the brain during pregnancy that support the emergence of new maternal behaviours. The idea of adaptive plasticity in pregnancy is at odds with the notion of "baby brain", in which pregnant women describe the onset of forgetfulness. While inconsistent evidence for memory deficits during pregnancy has been reported, few studies have investigated spatial associative memory (which is consistently enhanced in studies of pregnant rodents). Moreover, most studies assess domain-general stimuli, which might miss adaptations specific to parent-relevant stimuli. In the present study, we examined the retention of spatial associative memory for parenting-relevant and non-parenting-relevant stimuli across 4-weeks in a sample of women in their third trimester of pregnancy, and compared their performance to a sample of never pregnant women. We demonstrated that relative to never pregnant women, pregnant women exhibited enhanced long-term retention of object-scene-location associations (spatial associative memory), as well as better initial learning about parenting-relevant, relative to non-parenting-relevant, stimuli. Thus, similar to studies in rodents, cognitive improvements were seen during pregnancy in humans, and those improvements were specific to the domain of spatial associative retention, and in the recognition of stimuli relevant to parenting.

Shifting children's attentional focus to emotions during art museum experiences.

Art exposure can influence children's emotional growth, but little is known about tools that aid emotional development in art museums. We implemented attentional and social manipulations to test whether (1) modifications to unscripted instructions and (2) caregiver prompts shape children's attentional focus towards either the emotional or elemental content (e.g., colour and medium) of paintings. These manipulations occurred within an on-going art museum education programme. Afterwards, children's (N = 60; ages 3-13 years) attentional focus towards emotions or elements was assessed by asking them to select words that best described the art. Children focused on emotion more, but the instructional manipulation successfully influenced word choices towards the targeted focus. Caregiver prompts also influenced focus towards the elements and away from emotions. These findings highlight that children's attention to art's emotional content can be altered by social context, which here was demonstrated within a museum programme.

Mosaic PRKACA duplication causing a novel and distinct phenotype of early-onset Cushing's syndrome and acral cutaneous mucinosis.

SIGNIFICANCE STATEMENT: We describe a mosaic PRKACA duplication in a young infant who presented with a Carney-like complex: bilateral non-pigmented micronodular adrenal hyperplasia, severe early-onset Cushing's syndrome, and distinct acral soft tissue overgrowth due to cutaneous mucinosis. This represents a novel manifestation of PRKACA disruption and broadens the extra-adrenal phenotype of PRKACA-associated Cushing's syndrome. Our data suggest that Cushing's syndrome phenotypes arising from somatic and germline PRKACA abnormalities can exist on a spectrum. We emphasise the value of ascertaining a genetic diagnosis for PRKACA-mediated adrenal and extra-adrenal disease to guide individualised and targeted care.

Human threat learning is associated with gut microbiota composition.

The ability to learn about threat and safety is critical for survival. Studies in rodent models have shown that the gut microbiota can modulate such behaviors. In humans, evidence showing an association with threat or extinction learning is lacking. Here, we tested whether individual variability in threat and extinction learning was related to gut microbiota composition in healthy adults. We found that threat, but not extinction learning, varies with individuals' microbiome composition. Our results provide evidence that the gut microbiota is associated with excitatory threat learning across species.

Parenting under pressure: A mixed-methods investigation of the impact of COVID-19 on family life.

BACKGROUND: development and implementation of effective family-based psychosocial intervention and treatment strategies during COVID-19 will require a detailed understanding of how the virus has impacted the lives of families. METHODS: written reports on the life impacts of COVID-19 for parents (n = 56) and their children (n = 43), and a questionnaire assessing parent positive and negative affect, were collected between April and May 2020. An inductive approach was used to identify themes in written reports, followed by statistical analysis to explore associations between themes and changes in parent positive and negative affect pre- and post-writing. RESULTS: parents and children reported both positive and negative psychosocial impacts of the virus, though parents expressed a greater diversity of positive themes than children. Common themes reported by parents included concerns about the impact of COVID-19 on their children, health concerns for others, and the stressful balancing act of parenting, assisting with children's school work, and working from home. Many parents reported gratitude, and reflected on the upsides of the pandemic for family relationships and parent-child bonding. Parents who expressed gratitude reported a decrease in negative affect pre- to post-writing. Common child-reported themes included yearning to return to school, pandemic-related fears, and longing for social connection. LIMITATIONS: the sample included a cross-section of mostly White (non-Hispanic), dual income, well-educated mothers, primarily from the United States. CONCLUSIONS: both parents and children reported reduced wellbeing during the COVID-19 pandemic. Future research should focus on identifying how to fulfill children's social needs and lessen caregivers' burdens during this time.

Perinatal attention, memory and learning during sleep.

The perinatal brain is well equipped to react to the environment during sleep. Several lines of research in animals and humans prior to and immediately after birth have documented the capability to respond, to process and remember patterns of stimulation. In this article, we will summarize recent findings as well as previous work documenting the memory and learning capacities of the developing brain during sleep and wake states. The role of these sleep state dependent processes may play in the ability to adapt to the postnatal environment will be discussed.

Au cours de la période périnatale, le cerveau est en mesure de réagir à l'environnement pendant le sommeil. Plusieurs recherches menées avant et immédiatement après la naissance chez des modèles animaux non-humains (oiseaux et rongeurs) et chez les humains montrent en effet que des capacités de réponse opèrent envers des stimulations auditives et olfactives, de même que des traitements associatifs et mnésiques. Cet article résume les données récentes aussi bien que des travaux plus classiques sur les aptitudes d'apprentissage et de mémoire du cerveau en développement au cours des phases d'éveil aussi bien qu'au cours du sommeil. Le rôle de ces processus précoces d'acquisition pendant le sommeil est discuté dans le cadre de l'adaptation immédiate aux conditions sensorielles de l'environnement postnatal.