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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.

In the last decade, an abundance of research has utilized the National Institute of Mental Health (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.

Irritability is a transdiagnostic symptom dimension in developmental psychopathology, closely related to the Research Domain Criteria (RDoC) construct of frustrative nonreward. Consistent with the RDoC framework and calls for transdiagnostic, developmentally-sensitive assessment methods, we report data from a smartphone-based, naturalistic ecological momentary assessment (EMA) study of irritability. We assessed 109 children and adolescents (Mage = 12.55 years; 75.20% male) encompassing several diagnostic groups – disruptive mood dysregulation disorder (DMDD), attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ANX), healthy volunteers (HV). The participants rated symptoms three times per day for 1 week. Compliance with the EMA protocol was high. As tested using multilevel modeling, EMA ratings of irritability were strongly and consistently associated with in-clinic, gold-standard measures of irritability. Further, EMA ratings of irritability were significantly related to subjective frustration during a laboratory task eliciting frustrative nonreward. Irritability levels exhibited an expected graduated pattern across diagnostic groups, and the different EMA items measuring irritability were significantly associated with one another within all groups, supporting the transdiagnostic phenomenology of irritability. Additional analyses utilized EMA ratings of anxiety as a comparison with respect to convergent validity and transdiagnostic phenomenology. The results support new measurement tools that can be used in future studies of irritability and frustrative nonreward.

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.Eight studies met the rigorous inclusion criteria, which required direct assessment of interpretation bias in both youth and parent.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).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.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.

Early behaviors that differentiate later biomarkers for psychopathology can guide preventive efforts while also facilitating pathophysiological research. We test whether the 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. BI was assessed via maternal report and behavioral responses to novelty. Childhood irritability was assessed using the Child Behavior Checklist. At age 12, electroencephalogram (EEG) was recorded while children performed a flanker task to measure the 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 a 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.

Anxiety has been associated with reliance on reactive (stimulus-driven/reflexive) control strategies in response to conflict. However, this conclusion rests primarily on indirect evidence. Few studies utilize tasks that dissociate the use of reactive (‘just in time’) vs. proactive (anticipatory/preparatory) cognitive control strategies in response to conflict, and none examine children diagnosed with anxiety. The current study utilizes the AX-CPT, which dissociates these two types of cognitive control, to examine cognitive control in youth (ages 8–18) with and without an anxiety diagnosis (n = 56). Results illustrate that planful behavior, consistent with using a proactive strategy, varies by both age and anxiety symptoms. Young children (ages 8–12 years) with high anxiety exhibit significantly less planful behavior than similarly-aged children with low anxiety. These findings highlight the importance of considering how maturation influences relations between anxiety and performance on cognitive-control tasks and have implications for understanding the pathophysiology of anxiety in children.

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.

BACKGROUND: Widespread use of prostate-specific antigen (PSA) testing for prostate cancer (PC) detection has led to extensive overdiagnosis and overtreatment. Urine-based microRNA (miRNA) biomarkers could be useful in PC diagnosis and prognosis.OBJECTIVE: To train and validate urine-based microRNA (miRNA) biomarkers that may assist in PC diagnosis and prognosis.DESIGN, SETTING, AND PARTICIPANTS: We profiled the expression levels of 92 miRNAs via reverse transcriptase-poymerase chain reaction in cell-free urine samples from 29 patients with benign prostatic hyperplasia (BPH) and 215 patients with clinically localized PC (cohort 1). Our findings were validated in an independent cohort of 29 BPH patients and 220 patients with clinically localized PC (cohort 2).RESULTS AND LIMITATIONS: We identified and validated several deregulated miRNAs in urine samples from PC patients. In addition, we trained a novel diagnostic three-miRNA model (miR-222-3p*miR-24-3p/miR-30c-5p) that distinguished BPH and PC patients with an area under the curve (AUC) of 0.95 in cohort 1, and was successfully validated in cohort 2 (AUC 0.89). Furthermore, we trained a novel prognostic three-miRNA model (miR-125b-5p*let-7a-5p/miR-151-5p) that predicted time to biochemical recurrence after radical prostatectomy independently of routine clinicopathological parameters in cohort 1, and was successfully validated in cohort 2.CONCLUSIONS: Future clinical implementation of our novel diagnostic and prognostic three-miRNA signatures could help in primary diagnosis of PC and guide treatment decisions. Further validation studies are warranted.PATIENT SUMMARY: Using two large patient cohorts, we searched for novel prostate cancer biomarkers in urine. We found two new sets of microRNA biomarkers in urine that could accurately predict the presence of prostate cancer and the likelihood of recurrence after prostatectomy. Further studies are needed before an actual clinical test can be developed.

Objective To systematically review the literature reporting outcomes of augmentative family-based treatment (FBT) interventions for adolescents with restrictive eating disorders (EDs). Method Articles were identified through a systematic search of five electronic databases (PsycINFO, MEDLINE, EMBASE, CINAHL, Cochrane Database). Results Thirty articles were included, reporting on FBT augmentations featuring adjunctive treatment components, modified treatment structure and/or content with adherence to FBT principles, and adaptations allowing FBT delivery in different settings. All reported significant improvements in weight and/or ED symptoms at end-of-treatment, although few compared augmentative and standard FBT interventions and good quality follow-up data was generally lacking. Conclusions There is early evidence for the effectiveness of augmentative FBT-based approaches in facilitating weight and/or ED symptom improvements for adolescents with restrictive EDs. There remains a lack of robust evidence demonstrating superior effects of such approaches over standard FBT, and further controlled studies are required to expand on the current evidence. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

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.

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.