Leveraging multivariate approaches to advance the science of early-life adversity.

Since the landmark Adverse Childhood Experiences (ACEs) study, adversity research has expanded to more precisely account for the multifaceted nature of adverse experiences. The complex data structures and interrelated nature of adversity data require robust multivariate statistical methods, and recent methodological and statistical innovations have facilitated advancements in research on childhood adversity. Here, we provide an overview of a subset of multivariate methods that we believe hold particular promise for advancing the field's understanding of early-life adversity, and discuss how these approaches can be practically applied to explore different research questions. This review covers data-driven or unsupervised approaches (including dimensionality reduction and person-centered clustering/subtype identification) as well as supervised/prediction-based approaches (including linear and tree-based models and neural networks). For each, we highlight studies that have effectively applied the method to provide novel insight into early-life adversity. Taken together, we hope this review serves as a resource to adversity researchers looking to expand upon the cumulative approach described in the original ACEs study, thereby advancing the field's understanding of the complexity of adversity and related developmental consequences.

Reforming clinical psychological science training: The importance of collaborative decision-making with trainees.

To effectively address the staggering burden of mental illness, clinical psychological science will need to face some uncomfortable truths about current training practices. In a commentary authored by 23 current or recent trainees, Palitsky and colleagues highlight a number of urgent challenges facing today's clinical interns. They provide a thoughtful framework for reform, with specific recommendations and guiding questions for a broad spectrum of stakeholders. Key suggestions are applicable to the entire sequence of clinical training. While there is cause for cautious optimism, overcoming these systemic barriers will require a coordinated, all-hands approach and a more collaborative approach to policy-making.

Hippocampal Involvement in Safety Signal Learning Varies With Anxiety Among Healthy Adults.

Background: Safety signal learning (SSL), based on conditioned inhibition of fear in the presence of learned safety, can effectively attenuate threat responses in animal models and humans. Difficulty regulating threat responses is a core feature of anxiety disorders, suggesting that SSL may provide a novel mechanism for fear reduction. Cross-species evidence suggests that SSL involves functional connectivity between the anterior hippocampus and the dorsal anterior cingulate cortex. However, the neural mechanisms supporting SSL have not been examined in relation to trait anxiety or while controlling for the effect of novelty. Methods: Here, we investigated the neural mechanisms involved in SSL and associations with trait anxiety in a sample of 64 healthy (non-clinically anxious) adults (ages 18-30 years; 43 female, 21 male) using physiological, behavioral, and neuroimaging (functional magnetic resonance imaging) data collected during an SSL task. Results: During SSL, compared with individuals with lower trait anxiety, individuals with higher trait anxiety showed less fear reduction as well as altered hippocampal activation and hippocampal-dorsal anterior cingulate cortex functional connectivity, and lower inferior frontal gyrus and ventrolateral prefrontal cortex activation. Importantly, the findings show that SSL reduces threat responding, across learning and over and above the effect of novelty, and involves hippocampal activation. Conclusions: These findings provide new insights into the nature of SSL and suggest that there may be meaningful variation in SSL and related neural correlates as a function of trait anxiety, with implications for better understanding fear reduction and optimizing interventions for individuals with anxiety disorders.

Responding to threat: Associations between neural reactivity to and behavioral avoidance of threat in pediatric anxiety.

BACKGROUND: Despite broad recognition of the central role of avoidance in anxiety, a lack of specificity in its operationalization has hindered progress in understanding this clinically significant construct. The current study uses a multimodal approach to investigate how specific measures of avoidance relate to neural reactivity to threat in youth with anxiety disorders. METHODS: Children with anxiety disorders (ages 6-12 years; n = 65 for primary analyses) completed laboratory task- and clinician-based measures of avoidance, as well as a functional magnetic resonance imaging task probing neural reactivity to threat. Primary analyses examined the ventral anterior insula (vAI), amygdala, and ventromedial prefrontal cortex (vmPFC). RESULTS: Significant but distinct patterns of association with task- versus clinician-based measures of avoidance emerged. Clinician-rated avoidance was negatively associated with right and left vAI reactivity to threat, whereas laboratory-based avoidance was positively associated with right vAI reactivity to threat. Moreover, left vAI-right amygdala and bilateral vmPFC-right amygdala functional connectivity were negatively associated with clinician-rated avoidance but not laboratory-based avoidance. LIMITATIONS: These results should be considered in the context of the restricted range of our treatment-seeking sample, which limits the ability to draw conclusions about these associations across children with a broader range of symptomatology. In addition, the limited racial and ethnic diversity of our sample may limit the generalizability of findings. CONCLUSION: These findings mark an important step towards bridging neural findings and behavioral patterns using a multimodal approach. Advancing understanding of behavioral avoidance in pediatric anxiety may guide future treatment optimization by identifying individual-specific targets for treatment.

Neural Circuit Markers of Familial Risk for Depression Among Healthy Youths in the Adolescent Brain Cognitive Development Study.

BACKGROUND: Family history of depression is a robust predictor of early-onset depression, which may confer risk through alterations in neural circuits that have been implicated in reward and emotional processing. These alterations may be evident in youths who are at familial risk for depression but who do not currently have depression. However, the identification of robust and replicable findings has been hindered by few studies and small sample sizes. In the current study, we sought to identify functional connectivity (FC) patterns associated with familial risk for depression. METHODS: Participants included healthy (i.e., no lifetime psychiatric diagnoses) youths at high familial risk for depression (HR) (n = 754; at least one parent with a history of depression) and healthy youths at low familial risk for psychiatric problems (LR) (n = 1745; no parental history of psychopathology) who were 9 to 10 years of age and from the Adolescent Brain Cognitive Development (ABCD) Study sample. We conducted whole-brain seed-to-voxel analyses to examine group differences in resting-state FC with the amygdala, caudate, nucleus accumbens, and putamen. We hypothesized that HR youths would exhibit global amygdala hyperconnectivity and striatal hypoconnectivity patterns primarily driven by maternal risk. RESULTS: HR youths exhibited weaker caudate-angular gyrus FC than LR youths (α = 0.04, Cohen's d = 0.17). HR youths with a history of maternal depression specifically exhibited weaker caudate-angular gyrus FC (α = 0.03, Cohen's d = 0.19) as well as weaker caudate-dorsolateral prefrontal cortex FC (α = 0.04, Cohen's d = 0.21) than LR youths. CONCLUSIONS: Weaker striatal connectivity may be related to heightened familial risk for depression, primarily driven by maternal history. Identifying brain-based markers of depression risk in youths can inform approaches to improving early detection, diagnosis, and treatment.

Multivariate links between the developmental timing of adversity exposure and white matter tract integrity in adulthood.

Early-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health. The present study leverages sparse canonical correlation analysis to characterize modes of covariation between age of adversity exposure and the integrity of white matter tracts throughout the brain in a sample of 107 adults. We find that adversity exposure during middle childhood (ages 5-6 and 8-9 in particular) is consistently linked with alterations in white matter tract integrity, such that tracts supporting sensorimotor functions display higher integrity in relation to adversity exposure while tracts supporting cortico-cortical communication display lower integrity. Further, latent patterns of tract integrity linked with adversity experienced across preschool age and middle childhood (ages 4-9) were associated with trauma-related symptoms in adulthood. Our findings underscore that adversity exposure may differentially affect white matter in a function- and developmental-timing specific manner and suggest that adversity experienced between ages 4-9 may shape the development of global white matter tracts in ways that are relevant for adult mental health.

Validation of an electronic self-administered version of the Dimensional Inventory of Stress and Trauma Across the Lifespan in a large sample of young adults.

Recent advances in the dimensional assessment of traumatic stress have initiated research examining correlates of exposure to specific features of stress. However, existing tools require intensive, in-person, clinician administration to generate the rich phenotypic data required for such analyses. These approaches are time consuming, costly, and substantially restrict the degree to which assessment tools can be disseminated in large-scale studies, constraining the refinement of existing dimensional models of early adversity. Here, we present an electronic adaptation of the Dimensional Inventory of Stress and Trauma Across the Lifespan (DISTAL), called the DISTAL-Electronic (DISTAL-E), present descriptive statistics drawn from a large sample of N = 500 young adult participants who completed the novel measure, and provide information about its psychometric properties. Results suggest that the DISTAL-E adequately assesses the following dimensional indices of traumatic stress exposure: type, chronicity, age of onset, severity, proximity, caregiver involvement, controllability, predictability, betrayal, threat, and deprivation and that it has excellent content and convergent validity and good test-retest reliability over a 7-11 day period. Although the development of the DISTAL-E facilitates the broad assessment of dimensions of stress exposure in large-scale datasets and has the potential to increase access to stress-related research to a wider group of participants who may not be able to access clinical research in traditional, in-person, clinic-based settings, the generalizability of results of the present study may be constrained by the fact that study participants were primarily White, educated, and with middle-to-high income. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Leveraging the developmental neuroscience of caregiving to promote resilience among youth exposed to adversity.

Early adversity is a major risk factor for the emergence of psychopathology across development. Identifying mechanisms that support resilience, or favorable mental health outcomes despite exposure to adversity, is critical for informing clinical intervention and guiding policy to promote youth mental health. Here we propose that caregivers play a central role in fostering resilience among children exposed to adversity via caregiving influences on children's corticolimbic circuitry and emotional functioning. We first delineate the numerous ways that caregivers support youth emotional learning and regulation and describe how early attachment lays the foundation for optimal caregiver support of youth emotional functioning in a developmental stage-specific manner. Second, we outline neural mechanisms by which caregivers foster resilience-namely, by modulating offspring corticolimbic circuitry to support emotion regulation and buffer stress reactivity. Next, we highlight the importance of developmental timing and sensitive periods in understanding caregiving-related mechanisms of resilience. Finally, we discuss clinical implications of this line of research and how findings can be translated to guide policy that promotes the well-being of youth and families.

Extinction Learning Across Development: Neurodevelopmental Changes and Implications for Pediatric Anxiety Disorders.

Alterations in extinction learning relate to the development and maintenance of anxiety disorders across the lifespan. While exposure therapy, based on principles of extinction, can be highly effective for treating anxiety, many patients do not show sufficient improvement following treatment. In particular, evidence suggests that exposure therapy does not work sufficiently for up to 40% of children who receive this evidence-based treatment.Importantly, fear learning and extinction, as well as the neural circuitry supporting these processes, undergo dynamic changes across development. An improved understanding of developmental changes in extinction learning and the associated neural circuitry may help to identify targets to improve treatment response in clinically anxious children and adolescents. In this chapter, we provide a brief overview of methods used to study fear learning and extinction in developmental populations. We then review what is currently known about the developmental changes that occur in extinction learning and related neural circuitry. We end this chapter with a discussion of the implications of these neurodevelopmental changes for the characterization and treatment of pediatric anxiety disorders.

Characterizing experiential elements of early-life stress to inform resilience: Buffering effects of controllability and predictability and the importance of their timing.

Key theoretical frameworks have proposed that examining the impact of exposure to specific dimensions of stress at specific developmental periods is likely to yield important insight into processes of risk and resilience. Utilizing a sample of N = 549 young adults who provided a detailed retrospective history of their lifetime exposure to numerous dimensions of traumatic stress and ratings of their current trauma-related symptomatology via completion of an online survey, here we test whether an individual's perception of their lifetime stress as either controllable or predictable buffered the impact of exposure on trauma-related symptomatology assessed in adulthood. Further, we tested whether this moderation effect differed when evaluated in the context of early childhood, middle childhood, adolescence, and young adulthood stress. Consistent with hypotheses, results highlight both stressor controllability and stressor predictability as buffering the impact of traumatic stress exposure on trauma-related symptomatology and suggest that the potency of this buffering effect varies across unique developmental periods. Leveraging dimensional ratings of lifetime stress exposure to probe heterogeneity in outcomes following stress - and, critically, considering interactions between dimensions of exposure and the developmental period when stress occurred - is likely to yield increased understanding of risk and resilience following traumatic stress.

Characterizing the dimensional structure of early-life adversity in the Adolescent Brain Cognitive Development (ABCD) Study.

Early-life adversity has profound consequences for youth neurodevelopment and adjustment; however, experiences of adversity are heterogeneous and interrelated in complex ways that can be difficult to operationalize and organize in developmental research. We sought to characterize the underlying dimensional structure of co-occurring adverse experiences among a subset of youth (ages 9-10) from the Adolescent Brain Cognitive Development (ABCD) Study (N = 7115), a community sample of youth in the United States. We identified 60 environmental and experiential variables that reflect adverse experiences. Exploratory factor analysis identified 10 robust dimensions of early-life adversity co-occurrence, corresponding to conceptual domains such as caregiver substance use and biological caregiver separation, caregiver psychopathology, caregiver lack of support, and socioeconomic disadvantage / neighborhood lack of safety. These dimensions demonstrated distinct associations with internalizing problems, externalizing problems, cognitive flexibility, and inhibitory control. Non-metric multidimensional scaling characterized qualitative similarity among the 10 identified dimensions. Results supported a nonlinear three-dimensional structure representing early-life adversity, including continuous gradients of "perspective", "environmental uncertainty", and "acts of omission/commission". Our findings suggest that there are distinct dimensions of early-life adversity co-occurrence in the ABCD sample at baseline, and the resulting dimensions may have unique implications for neurodevelopment and youth behavior.

Development and validation of the Dimensional Inventory of Stress and Trauma Across the Lifespan (DISTAL): A novel assessment tool to facilitate the dimensional study of psychobiological sequelae of exposure to adversity.

Decades of research underscore the profound impact of adversity on brain and behavioral development. Recent theoretical models have highlighted the importance of considering specific features of adversity that may have dissociable effects at distinct developmental timepoints. However, existing measures do not query these dimensions in sufficient detail to support the proliferation of this approach. The Dimensional Inventory of Stress and Trauma Across the Lifespan (DISTAL) was developed with the aim to thoroughly and retrospectively assess the timing, severity (of exposure and reaction), type, persons involved, controllability, predictability, threat, deprivation, proximity, betrayal, and discrimination inherent in an individual's exposure to adversity. Here, we introduce this instrument, present descriptive statistics drawn from a sample of N = 187 adults who completed the DISTAL, and provide initial information about its psychometric properties. This novel measure facilitates the expansion of research focused on assessing the relative impact of exposure to key dimensions of adversity on the brain and behavior across development.

Consensus design of a calibration experiment for human fear conditioning.

Fear conditioning is a widely used laboratory model to investigate learning, memory, and psychopathology across species. The quantification of learning in this paradigm is heterogeneous in humans and psychometric properties of different quantification methods can be difficult to establish. To overcome this obstacle, calibration is a standard metrological procedure in which well-defined values of a latent variable are generated in an established experimental paradigm. These intended values then serve as validity criterion to rank methods. Here, we develop a calibration protocol for human fear conditioning. Based on a literature review, series of workshops, and survey of N = 96 experts, we propose a calibration experiment and settings for 25 design variables to calibrate the measurement of fear conditioning. Design variables were chosen to be as theory-free as possible and allow wide applicability in different experimental contexts. Besides establishing a specific calibration procedure, the general calibration process we outline may serve as a blueprint for calibration efforts in other subfields of behavioral neuroscience that need measurement refinement.

Affective language spreads between anxious children and their mothers during a challenging puzzle task.

Humans influence each other's emotions. The spread of emotion is well documented across behavioral, psychophysiological, and neuroscientific levels of analysis, but might this influence also be evident in language (e.g., are people more likely to use emotion words after hearing someone else use them)? The current study tests whether mothers and children influence each other's use of affective language. From 2018 to 2020, children aged 6-12 who met diagnostic criteria for anxiety disorders and their mothers (N = 93 dyads) completed a challenging puzzle task while being video recorded. Analyses of transcriptions revealed that mothers and children indeed influenced each other's language. Bidirectional influence was observed for use of negative affect words: Mothers were more likely to use negative affect words if their child had just used negative affect words (over and above mothers' own language on their previous turn), and children were similarly influenced by mother affect word use. A similar bidirectional relation emerged for linguistic distance, a measure related to effective emotion regulation and mental health. However, the significance of the child-to-mother direction of influence for these two variables varied depending on correction threshold and should thus be verified in future research. Nonetheless, these findings extend understanding of emotional influence by showing turn-by-turn relations between the use of affective language. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Managing fear and anxiety in development: A framework for understanding the neurodevelopment of emotion regulation capacity and tendency.

How we manage emotional responses to environmental threats is central to mental health, as difficulties regulating threat-related distress can blossom into symptoms of anxiety disorders. Given that anxiety disorders emerge early in the lifespan, it is crucial we understand the multi-level processes that support effective regulation of distress. Scholars have given increased attention to behavioral and neural development of emotion regulation abilities, particularly cognitive reappraisal capacity (i.e., how strongly one can down-regulate negative affect by reinterpreting a situation to change one's emotions). However, this work has not been well integrated with research on regulatory tendency (i.e., how often one spontaneously regulates emotion in daily life). Here, we review research on the development of both emotion regulation capacity and tendency. We then propose a framework for testing hypotheses and eventually constructing a neurodevelopmental model of both dimensions of emotion regulation. Clarifying how the brain supports both effective and frequent regulation of threat-related distress across development is crucial to identifying multi-level signs of dysregulation and developing interventions that support youth mental health.

Parents' emotion suppression exacerbates the effect of COVID-19 stress on youth internalizing symptomatology.

The COVID-19 pandemic has resulted in heightened stress for families in the United States, and exposure to pandemic-related stress has been found to confer risk for mental health problems among both children and parents. To isolate risk and protective factors for children living through the ongoing pandemic, several studies have begun to examine family-level factors that may exacerbate or buffer the impact of exposure to COVID-19-related stress on children's symptomatology. Building upon the extant literature documenting associations between parents' emotion regulation and children's mental health, especially during times of stress, the present study aimed to examine parents' regulation of their own emotions as a potential moderator of the association between children's exposure to family-level COVID-19-related stress and internalizing and externalizing problems. Results suggest that parents' regulation of their own emotions using expressive suppression, specifically, may exacerbate the effect of exposure to pandemic-related stress on children's internalizing problems, but not externalizing problems. Results highlight the importance of prioritizing parents' mental health and self-regulation in prevention and intervention efforts aimed at improving family-wide mental health outcomes during public health crises that place family systems under significant stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of perceived threats on mental health, social, and neurocognitive youth outcomes: A multicontextual, person-centered approach.

Perceived threat in youth's environments can elevate risk for mental health, social, and neurocognitive difficulties throughout the lifespan. However, few studies examine variability in youth's perceptions of threat across multiple contexts or evaluate outcomes across multiple domains, ultimately limiting our understanding of specific risks associated with perceived threats in different contexts. This study examined associations between perceived threat in youth's neighborhood, school, and family contexts at ages 9-10 and mental health, social, and neurocognitive outcomes at ages 11-12 within a large US cohort (N = 5525) enrolled in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). Latent profile analysis revealed four distinct profiles: Low Threat in all contexts, Elevated Family Threat, Elevated Neighborhood Threat, and Elevated Threat in all contexts. Mixed-effect models and post hoc pairwise comparisons showed that youth in Elevated Threat profile had poorer mental health and social outcomes 2 years later. Youth in the Elevated Family Threat profile uniquely showed increased disruptive behavior symptoms, whereas youth in the Elevated Neighborhood Threat profile predominantly displayed increased sleep problems and worse neurocognitive outcomes 2 years later. Together, findings highlight the importance of considering perceptions of threat across multiple contexts to achieve a more nuanced developmental picture.

How Caregivers Support Children's Emotion Regulation: Construct Validation of the Parental Assistance With Child Emotion Regulation (PACER) Questionnaire.

Caregivers play a crucial role in supporting the development of their children's emotion regulation. This study validated the Parental Assistance with Child Emotion Regulation (PACER) Questionnaire in a sample of 491 caregivers (M = 32.89 years) of young children ≤ 5 years. Exploratory structural equation modeling provided evidence of the instrument's ability to assess parental support for 10 distinct emotion regulation strategies that match the intended design of the instrument. Latent profile analysis revealed three distinct caregiver profiles characterized by above-average support for strategies that previously have been shown to be predictive of adaptive outcomes, maladaptive outcomes, or mixed-outcomes, respectively. Results add to existing literature that suggests the PACER is a valid and reliable assessment of caregiver-implemented support of emotion regulation strategies for children ≤ 5 years old. Evidence of distinct caregiver profiles highlights opportunities for prevention and intervention efforts to bolster extrinsic support for adaptive emotion regulation strategies. This instrument may be well-suited to capturing changes throughout the early developmental period, in addition to monitoring caregiver-facing interventions promoting optimal emotion regulation in children.