Early‐life stress confers profound and lasting risk for developing cognitive, social, emotional, and physical health problems. The effects of stress on the developing brain contribute to this risk, with frontolimbic circuitry particularly susceptible to early experiences, possibly due to its innervation with glucocorticoid receptors and the timing of frontolimbic circuit maturation. To date, the majority of studies on stress and frontolimbic circuitry have employed a categorical approach, comparing stress‐exposed versus non‐stress‐exposed youth. However, there is vast heterogeneity in the nature of stress exposure and in outcomes. Recent forays into understanding the psychobiological effects of stress have employed a dimensional approach focused on experiential, environmental, and temporal factors that influence the association between stress and subsequent vulnerability. This review highlights empirical findings that inform a dimensional approach to understanding the effects of stress on frontolimbic circuitry. We identify the timing, type, severity, controllability, and predictability of stress, and the degree to which a caregiver is involved, as specific features of stress that may play a substantial role in differential outcomes. We propose a framework for the effects of these features of stress on frontolimbic development that may partially determine how heterogeneity in stress exposure influences this circuitry and, ultimately, mental health.

Heightened fear and inefficient safety learning are key features of fear and anxiety disorders. Evidence-based interventions for anxiety disorders, such as cognitive behavioral therapy, primarily rely on mechanisms of fear extinction. However, up to 50% of clinically anxious individuals do not respond to current evidence-based treatment, suggesting a critical need for new interventions based on alternative neurobiological pathways. Using parallel human and rodent conditioned inhibition paradigms alongside brain imaging methodologies, we investigated neural activity patterns in the ventral hippocampus in response to stimuli predictive of threat or safety and compound cues to test inhibition via safety in the presence of threat. Distinct hippocampal responses to threat, safety, and compound cues suggest that the ventral hippocampus is involved in conditioned inhibition in both mice and humans. Moreover, unique response patterns within target-differentiated subpopulations of ventral hippocampal neurons identify a circuit by which fear may be inhibited via safety. Specifically, ventral hippocampal neurons projecting to the prelimbic cortex, but not to the infralimbic cortex or basolateral amygdala, were more active to safety and compound cues than threat cues, and activity correlated with freezing behavior in rodents. A corresponding distinction was observed in humans: hippocampal–dorsal anterior cingulate cortex functional connectivity—but not hippocampal–anterior ventromedial prefrontal cortex or hippocampal–basolateral amygdala connectivity—differentiated between threat, safety, and compound conditions. These findings highlight the potential to enhance treatment for anxiety disorders by targeting an alternative neural mechanism through safety signal learning.

Nearly all families in the United States were exposed to varying degrees of stress related to the COVID-19 pandemic during the spring of 2020. Building on previous research documenting the pernicious effects of stress on youth mental health, we aimed to test the effects of exposure to COVID-19-related stress on youth symptomatology. Further, in light of evidence suggesting that parents play an important role in buffering children from environmental stress, we assessed how specific parental behaviors (i.e., parental emotion socialization, maintenance of home routines, and availability to discuss the pandemic with child) contributed to effective parental buffering of the impact of pandemic-related stress on children’s symptomatology. Conversely, we tested whether parental anxiety-related symptomatology and parenting stress exacerbated the effect of children’s exposure to pandemic-related stress on children’s symptomatology. Results suggest that parents who engaged in relatively higher levels of emotion coaching of children’s negative emotions and who maintained more stable home routines during the pandemic were more effectively able to buffer the effects of pandemic-related stress on children’s symptomatology. Parents who reported higher levels of parenting stress and anxiety-related symptomatology were less likely to effectively buffer stress. Though interpretation of the findings is limited due to sole reliance on parental report and the cross-sectional study design due to the constraints of collecting data during a global pandemic, findings underscore the importance of assessing family-level factors when considering the impact of stressors on children’s symptomatology and highlight the need to support parents during global events that place families under significant stress.

Across species, caregivers exert a powerful influence on the neural and behavioral development of offspring. Increasingly, both animal and human research has highlighted specific patterns in caregivers’ behavior that may be especially important early in life, as well as neurobiological mechanisms linking early caregiving experiences with long-term affective behavior. Here we delineate evidence for an early sensitive period during infancy and toddlerhood when caregiver inputs that are predictable and associated with safety may become biologically embedded via influences on corticolimbic circuitry involved in emotion regulation. We propose that these caregiver signals prime corticolimbic circuitry to be receptive to later stage-specific caregiver influences, such as caregivers’ external regulation of children’s emotional reactivity. Following adversity that disrupts the predictability and safety associated with caregivers during this sensitive period, accelerated maturation of children’s corticolimbic circuitry may foreshorten the protracted period of plasticity and caregiver influence that is characteristic of humans. This work has implications for both prevention and intervention efforts targeting children exposed to adversity early in life.

Children make up over half of the world's migrants and refugees and face a multitude of traumatic experiences prior to, during, and following migration. Here, we focus on migrant children emigrating from Mexico and Central America to the United States and review trauma related to migration, as well as its implications for the mental health of migrant and refugee children. We then draw upon the early adversity literature to highlight potential behavioral and neurobiological sequalae of migration‐related trauma exposure, focusing on attachment, emotion regulation, and fear learning and extinction as transdiagnostic mechanisms underlying the development of internalizing and externalizing symptomatology following early‐life adversity. This review underscores the need for interdisciplinary efforts to both mitigate the effects of trauma faced by migrant and refugee youth emigrating from Mexico and Central America and, of primary importance, to prevent child exposure to trauma in the context of migration. Thus, we conclude by outlining policy recommendations aimed at improving the mental health of migrant and refugee youth.