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.

Neural responding during uncertain threat anticipation in pediatric anxiety.

Excessive fear responses to uncertain threat are a key feature of anxiety disorders (ADs), though most mechanistic work considers adults. As ADs onset in childhood and confer risk for later psychopathology, we sought to identify conditions of uncertain threat that distinguish 8-17-year-old youth with AD (n = 19) from those without AD (n = 33), and assess test-retest reliability of such responses in a companion sample of healthy adults across three sites (n = 19). In an adapted uncertainty of threat paradigm, visual cues parametrically signaled threat of aversive stimuli (fear faces) in 25 % increments (0 %, 25 %, 50 %, 100 %), while participants underwent functional magnetic resonance imaging (fMRI). We compared neural response elicited by cues signaling different degrees of probability regarding the subsequent delivery of fear faces. Overall, youth displayed greater engagement of bilateral inferior parietal cortex, fusiform gyrus, and lingual gyrus during uncertain threat anticipation in general. Relative to healthy youth, AD youth exhibited greater activation in ventrolateral prefrontal cortex (vlPFC)/BA47 during uncertain threat anticipation in general. Further, AD differed from healthy youth in scaling of ventral striatum/sgACC activation with threat probability and attenuated flexibility of responding during parametric uncertain threat. Complementing these results, significant, albeit modest, cross-site test-retest reliability in these regions was observed in an independent sample of healthy adults. While preliminary due to a small sample size, these findings suggest that during uncertainty of threat, AD youth engage vlPFC regions known to be involved in fear regulation, response inhibition, and cognitive control. Findings highlight the potential of isolating neural correlates of threat anticipation to guide treatment development and translational work in youth.

Building a Program of Expanded Peer Support for the Entire Health Care Team: No One Left Behind.

BACKGROUND: Medical errors can cause second victim syndrome (SVS) in caregivers. Literature describing the development of effective peer support programs is limited. This article describes the implementation of a peer support program for an entire health care system. METHODS: The research team initially trained 52 supporters representing all clinical areas throughout an urban academic quaternary care campus. Each then supported at-risk colleagues, raised awareness of SVS, and recruited others for training. Triggers for peer support expanded to include medical errors, unanticipated patient outcomes, inability to stop the progression of medical conditions, medical emergencies of colleagues, aggressive behavior by a patient/family member, and COVID-19 events. Data reporting supporters' efforts were summarized. After the initial 5-hour session, training was condensed into 2.5 hours. The effectiveness of these training sessions was assessed. The Second Victim Experience and Support Tool (SVEST) was used to assess program effectiveness three and nine months after implementation. RESULTS: By 18 months, a blended program was achieved with 149 supporters: 81 medical college and 68 hospital personnel. Providers received 46.5% of support efforts and hospital personnel 47.9%. The most common event supported was inability to stop the progression of medical conditions (24.5%). Both training sessions improved attendees' knowledge of SVS and improved their comfort with teaching others how to support a second victim. Both SVEST surveys showed that nonwork and supervisor support rated highest, followed by colleague support. Institution support rated lowest. CONCLUSION: The team successfully implemented a peer support program with trained supporters from various clinical disciplines for distressing events beyond medical errors.

Infant behavioral reactivity predicts change in amygdala volume 12 years later.

The current study examined the link between temperamental reactivity in infancy and amygdala development in middle childhood. A sample (n = 291) of four-month-old infants was assessed for infant temperament, and two groups were identified: those exhibiting negative reactivity (n = 116) and those exhibiting positive reactivity (n = 106). At 10 and 12 years of age structural imaging was completed on a subset of these participants (n = 75). Results indicate that, between 10 and 12 years of age, left amygdala volume increased more slowly in those with negative compared to positive reactive temperament. These results provide novel evidence linking early temperament to distinct patterns of brain development over middle childhood.

Anticipatory Threat Responding: Associations With Anxiety, Development, and Brain Structure.

BACKGROUND: While translational theories link neurodevelopmental changes in threat learning to pathological anxiety, findings from studies in patients inconsistently support these theories. This inconsistency may reflect difficulties in studying large patient samples with wide age ranges using consistent methods. A dearth of imaging data in patients further limits translational advances. We address these gaps through a psychophysiology and structural brain imaging study in a large sample of patients across the lifespan. METHODS: A total of 351 participants (8-50 years of age; 209 female subjects; 195 healthy participants and 156 medication-free, treatment-seeking patients with anxiety) completed a differential threat conditioning and extinction paradigm that has been validated in pediatric and adult populations. Skin conductance response indexed psychophysiological response to conditioned (CS+, CS-) and unconditioned threat stimuli. Structural magnetic resonance imaging data were available for 250 participants. Analyses tested anxiety and age associations with psychophysiological response in addition to associations between psychophysiology and brain structure. RESULTS: Regardless of age, patients and healthy comparison subjects demonstrated comparable differential threat conditioning and extinction. The magnitude of skin conductance response to both conditioned stimulus types differentiated patients from comparison subjects and covaried with dorsal prefrontal cortical thickness; structure-response associations were moderated by anxiety and age in several regions. Unconditioned responding was unrelated to anxiety and brain structure. CONCLUSIONS: Rather than impaired threat learning, pathological anxiety involves heightened skin conductance response to potential but not immediately present threats; this anxiety-related potentiation of anticipatory responding also relates to variation in brain structure. These findings inform theoretical considerations by highlighting anticipatory response to potential threat in anxiety.

Cortical Thickness and Subcortical Gray Matter Volume in Pediatric Anxiety Disorders.

Perturbations in the prefrontal cortex (PFC), hippocampus, and amygdala are implicated in the development of anxiety disorders. However, most structural neuroimaging studies of patients with anxiety disorders utilize adult samples, and the few studies in youths examine small samples, primarily with volume-based measures. This study tested the hypothesis that cortical thickness of PFC regions and gray matter volume of the hippocampus and amygdala differ between pediatric anxiety disorder patients and healthy volunteers (HVs). High-resolution 3-Tesla T1-weighted MRI scans were acquired in 151 youths (75 anxious, 76 HV; ages 8-18). Analyses tested associations of brain structure with anxiety diagnosis and severity across both groups, as well as response to cognitive-behavioral therapy in a subset of 53 patients. Cortical thickness was evaluated both within an a priori PFC mask (small-volume corrected) and using an exploratory whole-brain-corrected (p<0.05) approach. Anxious relative to healthy youths exhibited thicker cortex in the left ventromedial PFC (vmPFC) and left precentral gyrus. Both anxiety diagnosis and symptom severity were associated with smaller right hippocampal volume. In patients, thinner cortex in parietal and occipital cortical regions was associated with worse treatment response. Pediatric anxiety was associated with structural differences in vmPFC and hippocampus, regions implicated in emotional processing and in developmental models of anxiety pathophysiology. Parietal and occipital cortical thickness were related to anxiety treatment response but not baseline anxiety.