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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 wellbeing of children and families through the COVID-19 pandemic and beyond. [ABSTRACT FROM AUTHOR]

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 andmedium) of paintings. Thesemanipulations 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. [ABSTRACT FROM AUTHOR]

Humans learn about their environments by observing others, including what to fear and what to trust. Observational fear learning may be especially important early in life when children turn to their parents to gather information about their world. Yet, the vast majority of empirical research on fear learning in youth has thus far focused on firsthand classical conditioning, which may fail to capture one of the primary means by which fears are acquired during development. To address this gap in the literature, the present study examined observational fear learning in youth (n = 33; age range: 6–17 years) as they watched videos of their parent and an "unfamiliar parent" (i.e., another participant's parent) undergo fear conditioning. Youth demonstrated stronger fear learning when observing their parent compared to an unfamiliar parent, as indicated by changes in their self‐reported liking of the stimuli to which their parents were conditioned (CS+, a geometric shape paired with an aversive noise; CS‐, a geometric shape never paired with an aversive noise) and amygdala responses. Parent trait anxiety was associated with youth learning better (i.e., reporting a stronger preference for the CS‐ relative to CS+), and exhibiting stronger medial prefrontal‐amygdala connectivity. Neuroimaging data were additionally acquired from a subset of parents during firsthand conditioning, and parental amygdala and mPFC activation were associated with youth's neural recruitment. Together, these results suggest that youth preferentially learn fears via observation of their parents, and this learning is associated with emotional traits and neural recruitment in parents. [ABSTRACT FROM AUTHOR]

Gastrointestinal and mental disorders are highly comorbid, and animal models have shown that both can be caused by early adversity (e.g., parental deprivation). Interactions between the brain and bacteria that live within the gastrointestinal system (the microbiome) underlie adversity–gastrointestinal–anxiety interactions, but these links have not been investigated during human development. In this study, we utilized data from a population of 344 youth (3–18 years old) who were raised with their biological parents or were exposed to early adverse caregiving experiences (i.e., institutional or foster care followed by international adoption) to explore adversity–gastrointestinal–anxiety associations. In Study 1, we demonstrated that previous adverse care experiences were associated with increased incidence of gastrointestinal symptoms in youth. Gastrointestinal symptoms were also associated with concurrent and future anxiety (measured across 5 years), and those gastrointestinal symptoms mediated the adversity–anxiety association at Time 1. In a subsample of children who provided both stool samples and functional magnetic resonance imaging of the brain (Study 2, which was a "proof-of-principle"), adversity was associated with changes in diversity (both alpha and beta) of microbial communities, and bacteria levels (adversity-associated and adversity-independent) were correlated with prefrontal cortex activation to emotional faces. Implications of these data for supporting youth mental health are discussed. [ABSTRACT FROM AUTHOR]

Highlights: [•] Infantile amnesia is an underutilized approach to studying memory. [•] Developmental changes in molecular balance may underlie infantile amnesia. [•] Manipulations that affect infantile amnesia may provide insights into engram. [•] Infantile amnesia may be a useful model of forgetting in aging. [ABSTRACT FROM AUTHOR]

Adolescence is a period of heightened susceptibility to anxiety disorders, yet we have little experimental evidence on what factors may lead to psychopathology in adolescence. Preclinical models of extinction are commonly used to study the treatment of anxiety symptoms. Interestingly, recent research has shown that there are fundamental changes in the process of extinction across development, which may have implications for our understanding of psychopathology across the lifespan. Specifically, this research shows that the process of extinction parallels the nonlinear function of prefrontal cortex development, such that extinction behaviour is similar in juvenile and adult rats, but involves different processes in infancy and adolescence (periods of rapid growth and pruning, respectively). Our previous studies have shown that early-life stress accelerates the transition between infant and juvenile extinction systems. In the current series of experiments, we examined whether the same early-life stress, maternal separation (MS), would lead to an earlier transition between the juvenile and adolescent extinction systems, and between the adolescent and adult extinction systems. We show that MS adolescent rats exhibit more adult-like extinction behaviour, and that adolescent-like extinction emerges earlier in development (i.e. in pre-adolescent rats). These results may have important implications for the understanding and treatment of anxiety symptoms in adolescent populations. [ABSTRACT FROM AUTHOR]

• Maternal separation did not accelerate maturation of PNNs in amygdala or PFC. • Maternal separation did not affect PV density in infant and juveniles. • No sex differences were observed in effects of maternal separation on PNNs or PV. • Impact of early adversity may be more easily seen with functional neural measures. Early life adversity impacts on a range of emotional, cognitive, and psychological processes. A recent theoretical model suggests that at least some of these effects are due to accelerated maturation of specific physiological systems and/or neural circuits. For example, maternal separation (MS), a model of early life adversity in rodents, accelerates maturation of memory systems, and here we examined its impact on maturation of perineuronal nets (PNNs) and parvalbumin (PV)-containing inhibitory interneurons. PNNs are specialized extracellular matrix structures suggested to be involved in stabilizing long-term memories and in the closure of a sensitive period in memory development. PV-containing inhibitory interneurons are the type of cell that PNNs preferentially surround, and are also thought to be involved in memory. In Experiment 1, with male rats, there was an increase in PNNs in both the amygdala and prefrontal cortex with age from infancy to juvenility. Contrary to prediction, MS had no impact on either PNN or PV expression. The same pattern was observed in female rats in Experiment 2. Taken together, these data show that the early maturation of memory in MS infants is not due to an accelerated maturation of PNNs or PV-containing cells in either the amygdala or prefrontal cortex. [ABSTRACT FROM AUTHOR]

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., (© 2024 John Wiley & Sons Ltd.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

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., (© 2022 The Authors.)

Introduction: Research has highlighted relationships between the micro-organisms that inhabit our gastrointestinal tract (oral and gut microbiota) with host mood and gastrointestinal functioning. Mental health disorders and functional gastrointestinal disorders co-occur at high rates, although the mechanisms underlying these associations remain unclear. The Bugs and Brains Study aims to investigate complex relationships between anxiety/depression and irritable bowel syndrome (IBS) in two ways. First, its primary component will compare the gut and oral microbiota in females with anxiety/depression and/or IBS relative to controls, and investigate underlying physiological, endocrine and immune factors, as well as associations with diet and psychosocial factors. In an ancillary component, the study will also investigate gastrointestinal and mental health symptoms in a larger sample, and explore relationships with diet, exercise, oral health, substance use, medical history, early life adversity and psychosocial factors., Methods and Analysis: The Bugs and Brains Study aims to recruit 160 females to the primary component: (1) 40 controls; (2) 40 participants with a depressive/anxiety disorder, but no IBS; (3) 40 participants with IBS, but no depressive/anxiety disorder and (4) 40 participants with both depressive/anxiety disorder and IBS. Participation is completed within 1 month, and involves comprehensive questionnaires, anthropometrics, a diagnostic clinical interview, collection of two saliva samples, and stool, urine and hair samples. This study aims to use a systems biology approach to characterise oral and gut microbial composition and function using 16S rRNA gene sequencing and nuclear MR spectroscopy. As part of the ancillary component, it will collect questionnaire data from 1000 participants aged 18-40 years, capturing mental health, gastrointestinal health, oral health, diet and psychosocial factors., Ethics and Dissemination: Approval was granted by the University of Melbourne Human Research Ethics Committee (#1749221). All participants voluntarily provided informed consent. Results will be published in peer-reviewed journals and presented at scientific conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Recent evidence has shown that pups exposed to maternal separation exhibit profound changes in their emotional development, for example, early emergence of adult-like fear retention and fear inhibition (Callaghan & Richardson, 2011; Callaghan & Richardson, 2012). Numerous studies have shown that maternal separation is also a significant stressor for the mother. However, no studies have examined how a mother's prior parenting experience affects emotion development of pups in her subsequent litters. In this study female rats were bred and were then separated from their pups (maternal separation, MS) or remained with their pups (standard rearing, SR). After those pups were weaned, females were bred again with all pups from the subsequent litters being standard reared. Hence, these subsequent litter pups had mothers that were either previously separated (MS) or not (SR) from their prior litter. Those pups underwent fear conditioning at postnatal Day 17 and tested for fear retention, or had their fear extinguished and then tested for the renewal effect. The results show that the MS infants respond similarly to infants that had been directly exposed to MS. That is, the MS infants exhibited better retention of fear and more relapse after extinction compared with SR infants. Further experiments demonstrated that MS rats were not more anxious than SR infants. Taken together, these experiments are the first to demonstrate that infant offspring exhibit atypical emotional development of fear conditioning (but not anxiety) as a consequence of their mother's prior exposure to stress. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

The importance of early experiences for mental health across the lifespan is well recognized. In particular, there is a strong association between adverse caregiving experiences and mental illness. However, relative to studies assessing outcomes in adults, there are far fewer studies assessing the earlier emerging manifestations of caregiving adversity during development. This lack of developmental research limits an understanding of the mechanisms that link adversity with mental illness. Adoption of a developmental approach to research in this field will yield greater insights into the factors that tie adversity to poor emotion function across a lifespan. In this review, we focus on recent findings that have used a developmental approach in the examination of mental health and early adversity. These studies are notable in that, across numerous species, they converge on the idea that early adversity leads to accelerated maturation of emotion circuits in the brain and in the behaviors supported by these regions. We propose that these 'stress acceleration' effects are evidence of early system adaptation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest to report.

Early experiences critically shape the structure and function of the brain. Perturbations in typical/species-expected early experiences are known to have profound neural effects, especially in regions important for emotional responding. Parental care is one species-expected stimulus that plays a fundamental role in the development of emotion neurocircuitry. Emerging evidence across species suggests that phasic variation in parental presence during the sensitive period of childhood affects the recruitment of emotional networks on a moment-to-moment basis. In addition, it appears that increasing independence from caregivers cues the termination of the sensitive period for environmental input into emotion network development. In this review, we examine how early parental care, the central nervous system, and behavior come together to form a 'neuro-environmental loop,' contributing to the formation of stable emotion regulation circuits. To achieve this end, we focus on the interaction of parental care and the developing amygdala-medial prefrontal cortex (mPFC) network-that is at the core of human emotional functioning. Using this model, we discuss how individual or group variations in parental independence, across chronic and brief timescales, might contribute to neural and emotional phenotypes that have implications for long-term mental health.

Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations., (© 2014 Wiley Periodicals, Inc.)

Unlike adult memories that can be remembered for many years, memories that are formed early in life are more fragile and susceptible to being forgotten (a phenomenon known as "infantile" or "childhood" amnesia). Nonetheless, decades of research in both humans and nonhuman animals demonstrate the importance of early life experiences on later physical, mental, and emotional functioning. This raises the question of how early memories can be so influential if they cannot be recalled. This review presents one potential solution to this paradox by considering what happens to an early memory after it has been forgotten. Specifically, we describe evidence showing that these forgotten early-acquired memories have not permanently decayed from storage. Instead, there appears to be a memory "trace" that persists in the face of forgetting which continues to affect a variety of behavioral responses later in life. Excitingly, the discovery of this physical trace will allow us to explore previously untestable issues in new ways, from whether forgetting is due to a failure in retrieval or storage to how memories can be recovered after extended periods of time. A greater understanding of the characteristics of this memory trace will provide novel insights into how some memories are left behind in childhood while others are carried with us, at least in some form, for a lifetime.

While early experiences are proposed to be important for the emergence of anxiety and other mental health problems, there is little empirical research examining the impact of such experiences on the development of emotional learning. Of the research that has been performed in this area, however, a complex picture has emerged in which the maturation of emotion circuits is influenced by the early experiences of the animal. For example, under typical laboratory rearing conditions infant rats rapidly forget learned fear associations (infantile amnesia) and express a form of extinction learning which is relapse-resistant (i.e., extinction in infant rats may be due to fear erasure). In contrast, adult rats exhibit very long-lasting memories of past learned fear associations, and express a form of extinction learning that is relapse-prone (i.e., the fear returns in a number of situations). However, when rats are reared under stressful conditions then they exhibit adult-like fear retention and extinction behaviors at an earlier stage of development (i.e., good retention of learned fear and relapse-prone extinction learning). In other words, under typical rearing conditions infant rats appear to be protected from exhibiting anxiety whereas after adverse rearing fear learning appears to make those infants more vulnerable to the later development of anxiety. While the effects of different experiences on infant rats' fear retention and extinction are becoming better documented, the mechanisms which mediate the early transition seen following stress remain unclear. Here we suggest that rearing stress may lead to an early maturation of the molecular and cellular signals shown to be involved in the closure of critical period plasticity in sensory modalities (e.g., maturation of GABAergic neurons, development of perineuronal nets), and speculate that these signals could be manipulated in adulthood to reopen infant forms of emotional learning (i.e., those that favor resilience).

Research first reported nearly 50 years ago demonstrated that infant and young animals (including humans) exhibit profoundly faster rates of forgetting (i.e., infantile amnesia) than do adults. In addition to these differences in retention, more recent research has shown that inhibition of fear learning is also very different in infancy than in adulthood. Specifically, extinction of fear early in life is much more resistant to relapse than is extinction later in life. Both of these findings suggest that young animals should be especially resilient to the emergence of mental health disorders, which appears to be at odds with the view that early-life experiences are particularly important for the development of later psychopathologies (such as anxiety disorders) and with the finding that the majority of anxiety disorders first emerge in adolescence or childhood. This apparent paradox might be resolved, however, if exposure to chronic stress early in life affects the maturation of the fear retention and extinction systems, leading to a faster transition to the adult form of each (i.e., long-lasting fear memories and relapse-prone extinction). In several recent studies we have found exactly this pattern; that is, infant rats exposed to maternal-separation stress exhibit adult-like fear and extinction learning early in development. Further, we have demonstrated that some of these effects can be mimicked by exposing the mother to the stress hormone corticosterone in their drinking water (in lieu of the separation procedure). These findings suggest that early-life exposure to stress and stress hormones may act as a general signal that can alter the developmental trajectory of emotional systems and potentially place animals at greater risk for the development of anxiety. The implications of these recent findings for our understanding of the developmental origins of health and disease, and for enhancing preventative and therapeutic treatments across the lifespan, are considered.