Development of Neural Mechanisms Underlying Threat Processing: Associations With Childhood Social Reticence and Adolescent Anxiety.

Background: Social reticence in early childhood is characterized by shy and anxiously avoidant behavior, and it confers risk for pediatric anxiety disorders later in development. Aberrant threat processing may play a critical role in this association between early reticent behavior and later psychopathology. The goal of this longitudinal study is to characterize developmental trajectories of neural mechanisms underlying threat processing and relate these trajectories to associations between early-childhood social reticence and adolescent anxiety. Methods: In this 16-year longitudinal study, social reticence was assessed from 2 to 7 years of age; anxiety symptoms and neural mechanisms during the dot-probe task were assessed at 10, 13, and 16 years of age. The sample included 144 participants: 71 children provided data at age 10 (43 girls, meanage = 10.62), 85 at age 13 (46 girls, meanage = 13.25), and 74 at age 16 (36 girls, meanage = 16.27). Results: A significant interaction manifested among social reticence, anxiety symptoms, and time, on functional connectivity between the left amygdala and the left dorsolateral prefrontal cortex, voxelwise p < .001, clusterwise familywise error p < .05. Children with high social reticence showed a negative association between amygdala-dorsolateral prefrontal cortex connectivity and anxiety symptoms with age, compared to children with low social reticence, suggesting distinct neurodevelopmental pathways to anxiety. Conclusions: These findings were present across all conditions, suggesting task-general effects in potential threat processing. Additionally, the timing of these neurodevelopmental pathways differed for children with high versus low social reticence, which could affect the timing of effective preventive interventions.

The role of anxiety and gender in anticipation and avoidance of naturalistic anxiety-provoking experiences during adolescence: An ecological momentary assessment study.

Objective: Anxiety symptoms often increase in late childhood/early adolescence, particularly among girls. However, few studies examine anxiety-relevant gender differences during anticipation and avoidance of naturalistic experiences during adolescence. The current study uses ecological momentary assessment (EMA) to examine associations among clinical anxiety, gender, anticipation, and attempted avoidance of person-specific anxiety-provoking experiences in youth ages 8-18. Method: 124 youth (73 girls) completed 7 consecutive days of EMA. Seventy participants (42 girls) met criteria for one or more anxiety disorders, while the remaining 54 were healthy controls (31 girls). Participants reported the experience that they were "most worried about happening that day" and completed ratings about that event including whether they attempted to avoid that experience. Multilevel models examined whether diagnostic group (anxious, healthy), gender (boys, girls), or their interaction predicted anticipatory ratings or avoidance of these experiences. Results: Analyses revealed significant diagnostic group by gender interactions for anticipatory ratings. Specifically, anxious girls reported greater worry and predicted more negative outcomes related to future experiences. However, only a main effect of diagnostic group emerged for attempted avoidance. Finally, anticipatory worry predicted higher rates of attempted avoidance, but this association did not vary by diagnostic group, gender, or their interaction. Conclusion: These findings extend the literature on the interplay of anticipation and avoidance to person-specific naturalistic experiences in pediatric anxiety. They reveal that anxious girls report more anticipatory anxiety and worry, while avoidance of real-world anxiety-provoking scenarios is a key concern for anxious youth independent of gender. By using EMA to examine person-specific anxiety-inducing experiences we can begin to understand how these processes and experiences unfold in the real world.

Is interpretation bias for threat content specific to youth anxiety symptoms/diagnoses? A systematic review and meta-analysis.

Anxiety is the most common mental health problem in youth. Numerous studies have identified that youth anxiety is associated with interpretation bias or the attribution of threatening meaning to ambiguity. Interpretation bias has been proposed as a mechanism underlying the development and maintenance of pediatric anxiety. Theoretically, interpretation bias should be content-specific to individual youth anxiety symptom domains. However, extant studies have reported conflicting findings of whether interpretation bias is indeed content specific to youth anxiety symptoms or diagnoses. The present meta-analysis aimed to synthesize the literature and answer the question: is the relationship between interpretation bias and anxiety content specific? Search of PubMed and PsycINFO databases from January 1, 1960 through May 28, 2019 yielded 9967 citations, of which 19 studies with 20 comparisons and 2976 participants met eligibility criteria. Meta-analysis with random effects models was conducted to examine an overall effect (Pearson r) between anxiety domain and content-specific interpretation bias in single sample studies, and an overall effect size difference (Cohen's d) in studies comparing anxious to non-anxious youth. Results support a content specific correlation between interpretation bias and anxiety symptom domain in single sample studies (r = 0.18, p = 0.03). However, it is currently undetermined whether this relationship holds in studies that compare the relationship between content-specific interpretation bias and anxiety in anxious versus non-anxious youth. A variety of methodologic considerations across studies are discussed, with implications for further investigation of interpretation bias and youth anxiety.

Like parent, like child: Is parent interpretation bias associated with their child's interpretation bias and anxiety? A systematic review and meta-analysis.

BACKGROUND: Anxiety disorders are the most prevalent psychiatric problem across the lifespan, with typical onset during the pediatric period. Prior literature has examined cognitive mechanisms associated with youth anxiety and identified interpretation bias, the threatening appraisal of ambiguity, as a ubiquitous correlate and likely mechanism. A small set of studies have examined interpretation bias and anxiety in parent-child dyads, although results about this potential relationship are conflicted. This systematic review and meta-analysis investigates the association between parent interpretation bias with child interpretation bias and child anxiety. METHODS: Eight studies met the rigorous inclusion criteria, which required direct assessment of interpretation bias in both youth and parent. RESULTS: Meta-analysis with a random effects model indicated a small and significant correlation between parent and child interpretation biases (r = 0.14, p < .01), as well as a small and significant correlation between parent interpretation bias and child anxiety (r =  = 0.20, p = .01). LIMITATIONS: As only eight studies were included in this meta-analysis, reflecting the state of the extant literature, it is possible that, as data accumulate and this work continues in the future, results may or may not be replicated. CONCLUSIONS: Despite variability in findings across the included empirical studies, the current meta-analysis suggests that a correlational relationship between parent interpretation bias and child bias/anxiety exists. This work has implications for conceptualizing parent interpretation bias as a possible explanatory mechanism underlying youth interpretation bias and anxiety.

The Transdiagnostic Origins of Anxiety and Depression During the Pediatric Period: Linking NIMH Research Domain Criteria (RDoC) Constructs to Ecological Systems.

In the last decade, an abundance of research has utilized the NIMH Research Domain Criteria (RDoC) framework to examine mechanisms underlying anxiety and depression in youth. However, relatively little work has examined how these mechanistic intrapersonal processes intersect with context during childhood and adolescence. The current paper covers reviews and meta-analyses that have linked RDoC-relevant constructs to ecological systems in internalizing problems in youth. Specifically, cognitive, biological, and affective factors within the RDoC framework were examined. Based on these reviews and some of the original empirical research they cover, we highlight the integral role of ecological factors to the RDoC framework in predicting onset and maintenance of internalizing problems in youth. Specific recommendations are provided for researchers using the RDoC framework to inform future research integrating ecological systems and development. We advocate for future research and research funding to focus on better integration of the environment and development into the RDoC framework.

Developmental pathways to social anxiety and irritability: The role of the ERN.

Early behaviors that differentiate later biomarkers for psychopathology can guide preventive efforts while also facilitating pathophysiological research. We tested whether error-related negativity (ERN) moderates the link between early behavior and later psychopathology in two early childhood phenotypes: behavioral inhibition and irritability. From ages 2 to 7 years, children (n = 291) were assessed longitudinally for behavioral inhibition (BI) and irritability. Behavioral inhibition was assessed via maternal report and behavioral responses to novelty. Childhood irritability was assessed using the Child Behavior Checklist. At age 12, an electroencephalogram (EEG) was recorded while children performed a flanker task to measure ERN, a neural indicator of error monitoring. Clinical assessments of anxiety and irritability were conducted using questionnaires (i.e., Screen for Child Anxiety Related Disorders and Affective Reactivity Index) and clinical interviews. Error monitoring interacted with early BI and early irritability to predict later psychopathology. Among children with high BI, an enhanced ERN predicted greater social anxiety at age 12. In contrast, children with high childhood irritability and blunted ERN predicted greater irritability at age 12. This converges with previous work and provides novel insight into the specificity of pathways associated with psychopathology.

Advancing clinical neuroscience through enhanced tools: Pediatric social anxiety as an example.

BACKGROUND: Clinical researchers face challenges when trying to quantify diverse processes engaged during social interactions. We report results from two studies, each demonstrating the potential utility of tools for examining processes engaged during social interactions. METHOD: In the first study, youth (n = 57) used a smartphone-based tool to rate mood and responses to social events. A subset (n = 20) completed the second, functional magnetic resonance imaging study. This second study related anxiety to error-evoked brain responses in two social conditions-while being observed and when alone. We also combined these tools to bridge clinical, social-contextual, and neural levels of measurement. RESULTS: Results from the first study showed an association between negatively-perceived social experiences and a range of negative emotions. In the second study there was a positive correlation during error monitoring between social-anxiety severity and context-specific activation of the pregenual anterior cingulate cortex. Finally, during imaging, the perceived quality of peer interactions as assessed using the smartphone-based tool, interacted with social context to predict levels of activation in the hippocampus and superior frontal gyrus. CONCLUSIONS: By improving measurement, enhanced tools may provide new means for studying relationships among anxiety, brain function, and social interactions.

Inhibitory control and emotion dysregulation: A framework for research on anxiety.

While emotional dysregulation is a broad construct, the current paper adopts a narrow approach to facilitate translational neuroscience research on pediatric anxiety. The paper first presents data on an adapted version of the antisaccade task and then integrates these data into a research framework. Data on an adapted version of the antisaccade task were collected in 57 youth, including 35 seeking treatment for an anxiety disorder. Associations were examined between performance on the antisaccade task and (a) age, (b) performance on other cognitive-control tasks (i.e., the stop-signal delay and flanker tasks), and (c) level of anxiety symptoms. Better performance on the antisaccade task occurred in older relative to younger subjects and correlated with better performance on the flanker task. Across the 57 youth, higher levels of anxiety correlated with shorter latency for correct antisaccades. These data can be placed within a three-step framework for translational neuroscience research. In the first step, a narrow index of emotion dysregulation is targeted. In the second step, this narrow index is linked to other correlated indicators of the same underlying narrow latent construct. In the third and final step, associations are examined with clinical outcomes and response to treatment.