Obsessive-Compulsive Symptoms: Baseline Prevalence, Comorbidity, and Implications in a Clinically Anxious Pediatric Sample.

Subclinical symptoms of obsessive-compulsive disorder (i.e., obsessive compulsive symptoms, or "OCS") cause functional impairment, including for youth without full-syndrome OCD. Further, despite high rates of OCS in youth with anxiety disorders, knowledge of OCS in the context of specific anxiety disorders is limited. The present study seeks to: (1) compare OCS in pediatric patients with anxiety disorders and healthy youth, (2) determine which categorical anxiety disorder(s) associate most with OCS, and (3) determine relationships between OCS with anxiety severity and impairment. Data on OCS, anxiety, and functional impairment were collected from 153 youth with anxiety disorders and 45 healthy controls, ages 7-17 years (M = 11.84, SD = 3.17). Findings indicated that patients had significantly more OCS than healthy controls. Among patients, GAD was a significant predictor of OCS as well as OCD risk. These results suggest that OCS should be a primary diagnostic and treatment consideration for youth who present in clinical settings with GAD.

Reliability of an ultrasound imaging acquisition procedure for examining osteoarthritis in the first metatarsophalangeal joint.

OBJECTIVE: Given the ability of ultrasound imaging (USI) to depict tissue-specific morphological changes before the onset of pain and before the point of irreversible structural damage, USI could play a fundamental role in earlier detection and assessment of foot osteoarthritis (OA). The current guidelines require further refinement of anatomical landmarks to establish a standardized imaging procedure to improve the interpretability and reproducibility between studies evaluating the first metatarsophalangeal joint (MTPJ). The aims were to develop an USI acquisition procedure and grading system to examine OA features in the first MTPJ and to determine intra-examiner and inter-examiner reliability of a newly developed USI acquisition procedure. DESIGN: Thirty participants with first MTPJ OA confirmed radiographically with the use of the La Trobe Foot Atlas were included. An experienced sonographer applied a newly developed USI procedure to examine the following features: joint effusion, synovial hypertrophy, synovitis, joint space narrowing, osteophytes, and cartilage thickness. A semiquantitative grading system was applied to all features. A continuous measure was also examined for osteophyte size, joint space narrowing, and cartilage thickness. To determine the intra-examiner and inter-examiner reliability, an experienced radiologist and sonographer applied the developed grading system to the images acquired from two imaging sessions. Intra-examiner and inter-examiner reliability were calculated using intraclass correlation coefficients (ICCs). RESULTS: ICCs for intra-examiner between session reliability ranged from 0.58 to 0.92 for semiquantitative grading and 0.39 to 0.94 for continuous measures. Joint effusion and osteophytes achieved the highest intra-examiner reliability (ICC = 0.78-0.94). ICCs for session one inter-examiner reliability ranged from 0.61 to 1.0 for semiquantitative grading; all continuous measures had an ICC of 1. ICCs for session two inter-examiner reliability ranged from 0.55 to 1.0 for semiquantitative grading and 0.9 to 0.97 for continuous measures. Inter-examiner reliability was good for grading joint effusion (ICC = 0.55-0.62) and was excellent for all other USI features (ICC = 0.77-1.0). CONCLUSION: The USI acquisition procedure and grading system are reliable in evaluating first MTPJ OA features in participants with radiologically confirmed OA. The study will inform the methodological development of an ultrasound atlas for grading the degree of osteoarthritic change in the first MTPJ.

Brain response to errors in children who stutter.

PURPOSE: Heightened rates of social anxiety have been reported in adults who stutter (AWS), but it is unclear whether anxiety is heightened also in children who stutter (CWS). Objective neurophysiological responses such as the error-related negativity (ERN) have been associated with anxiety, and ERN was reported to be increased in AWS. In this study, we examined whether ERN and error positivity (Pe) are increased in CWS. We further characterized ERN associations with age and anxiety in CWS relative to children who do not stutter (CWNS). METHODS: EEG data were recorded from twenty-four CWS and twenty-four matched CWNS aged 3-9 years as they performed a Go/No-Go task. Parent-reported anxiety, and child-reported speech-associated attitude measures were collected. Linear regression models tested the effects of age, group, and their interaction, and the effects of anxiety, group, and their interaction on ERN and Pe. RESULTS: Contrary to expectations, no ERN or Pe difference were observed between CWS and CWNS. However, larger ERN amplitudes were associated with older age in CWS but not CWNS, suggesting altered development of the error monitoring system in CWS. Association of Pe with anxiety also differed between groups: smaller Pe amplitudes were associated with higher level of parent-reported child anxiety in CWNS but not in CWS. Neither anxiety nor self-reported communication attitude differed between groups. CONCLUSIONS: Brain responses to errors were overall comparable between CWS and CWNS. However, CWS differed in how error monitoring responses varied with age and with anxiety levels. More research is warranted to examine how these factors contribute to persistent stuttering.

Anxiety Symptoms in Young Children Are Associated With a Maladaptive Neurobehavioral Profile of Error Responding.

BACKGROUND: Childhood anxiety symptoms have been linked to alterations in cognitive control and error processing, but the diverse findings on neural markers of anxiety in young children, which vary by severity and developmental stage, suggest the need for a wider perspective. Integrating new neural markers with established ones, such as the error-related negativity, the error positivity, and frontal theta, could clarify this association. Error-related alpha suppression (ERAS) is a recently proposed index of post-error attentional engagement that has not yet been explored in children with anxiety. METHODS: To identify neurobehavioral profiles of anxiety in young children by integrating ERAS with the error-related negativity, error positivity, frontal theta, and post-error performance indicators, we employed K-means clustering as an unsupervised multimetric approach. For this, we first aimed to confirm the presence and scalp distribution of ERAS in young children. We performed event-related potentials and spectral analysis of electroencephalogram data collected during a Go/NoGo task (Zoo Task) completed by 181 children (ages 4-7 years; 103 female) who were sampled from across the clinical-to-nonclinical range of anxiety severity using the Child Behavior Checklist. RESULTS: Results confirmed ERAS, showing lower post-error alpha power, maximal suppression at occipital sites, and less ERAS in younger children. K-means clustering revealed that high anxiety and younger age were associated with reduction in ERAS and frontal theta, less negative error-related negativity, enlarged error positivity, more post-error slowing, and reduced post-error accuracy. CONCLUSIONS: Our findings indicate a link between ERAS, maladaptive neural mechanisms of attention elicited by errors, and anxiety in young children, suggesting that anxiety may arise from or interfere with attention and error processing.

Neural Substrates of Emotion Processing and Cognitive Control Over Emotion in Youth Anxiety: An RDoC-Informed Study Across the Clinical to Nonclinical Continuum of Severity.

OBJECTIVE: Clinically anxious youth are hypervigilant to emotional stimuli and display difficulty shifting attention from emotional to nonemotional stimuli, suggesting impairments in cognitive control over emotion. However, it is unknown whether the neural substrates of such biases vary across the clinical-to-nonclinical range of anxiety or by age. METHOD: Youth aged 7 to 17 years with clinical anxiety (n = 119) or without an anxiety diagnosis (n = 41) matched emotional faces or matched shapes flanked by emotional face distractors during magnetic resonance imaging, probing emotion processing and cognitive control over emotion, respectively. Building from the National Institute of Mental Health Research Domain Criteria (RDoC) framework, clinically anxious youth were sampled across diagnostic categories, and non-clinically affected youth were sampled across minimal-to-subclinical severity. RESULTS: Across both conditions, anxiety severity was associated with hyperactivation in the right inferior parietal lobe, a substrate of hypervigilance. Brain-anxiety associations were also differentiated by attentional state; anxiety severity was associated with greater left ventrolateral prefrontal cortex activation during emotion processing (face matching) and greater activation in the left posterior superior temporal sulcus and temporoparietal junction (and slower responses) during cognitive control over emotion (shape matching). Age also moderated associations between anxiety and cognitive control over emotion, such that anxiety was associated with greater right thalamus and bilateral posterior cingulate cortex activation for children at younger and mean ages, but not for older youth. CONCLUSION: Aberrant function in brain regions implicated in stimulus-driven attention to emotional distractors may contribute to anxiety in youth. Results support the potential utility of attention modulation interventions for anxiety that are tailored to developmental stage. CLINICAL TRIAL REGISTRATION INFORMATION: Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety; https://clinicaltrials.gov; NCT02810171.

Development of an Ultrasound Imaging Atlas for Grading Osteoarthritis in the First Metatarsophalangeal Joint.

OBJECTIVE: Ultrasound (US) imaging may play a fundamental role in the earlier detection and assessment of first metatarsophalangeal joint (MTPJ) osteoarthritis (OA) because of its ability to depict tissue-specific morphologic changes before the point of irreversible structural damage. However, the role of US in supporting the diagnosis of OA in foot joints has not been clearly defined. The aims of this study were to develop a semiquantitative US atlas (the AUT ultrasound imaging [AUTUSI] atlas) to grade the degree of osteoarthritic change in the first MTPJ and to evaluate the intraexaminer and interexaminer reproducibility of using the atlas. METHODS: US images were obtained from 57 participants (30 participants with radiographically confirmed first MTPJ OA). The AUTUSI atlas supports the examination of grading joint effusion, synovial hypertrophy, synovitis, osteophytes, joint space narrowing, and cartilage thickness. Six examiners used the atlas to independently grade 24 US images across 2 sessions. Intraexaminer and interexaminer reproducibility were determined using percentage agreement and Gwet's AC2. RESULTS: Observations using the AUTUSI atlas demonstrated almost perfect-to-perfect interexaminer agreement (percentage agreement ranged from 96% to 100%, and Gwet's AC2 values ranged from 0.81 to 1.00) and moderate-to-perfect intraexaminer agreement (percentage agreement ranged from 67% to 100%, and Gwet's AC2 values ranged from 0.54 to 1.00). CONCLUSION: The AUTUSI atlas demonstrated excellent intraexaminer and interexaminer reproducibility for evaluating first MTPJ joint effusion, synovial hypertrophy, synovitis, joint space narrowing, osteophytes, and cartilage thickness. The AUTUSI atlas affords an opportunity to detect prognostic markers of OA earlier in the disease cascade and has the potential to advance understanding of the pathologic process of first MTPJ OA.

Activation of autoreactive lymphocytes in the lung by STING gain-of-function mutation expressing radioresistant cells.

Gain-of-function mutations in the dsDNA sensing adaptor STING lead to a severe autoinflammatory syndrome known as STING-associated vasculopathy with onset in Infancy (SAVI). SAVI patients develop interstitial lung disease (ILD) and produce autoantibodies that are commonly associated with systemic autoimmune diseases. Mice expressing the most common SAVI mutation STING V154M (VM) similarly develop ILD, but exhibit severe T and B cell lymphopenia, low serum Ig titers, and lack autoantibodies. Importantly, lethally irradiated VM hosts reconstituted with wildtype (WT) stem cells (WT→VM) still develop ILD. In this study, we find that WT→VM chimeras had restored B cell function, produced autoantibodies, and thereby recapitulated the loss of tolerance seen in SAVI patients. Lymphocytes derived from both WT and BCR or TCR transgenic (Tg) donors accumulated in the extravascular lung tissue of WT+Tg→VM mixed chimeras, but lymphocyte activation and germinal center formation required WT cells with a diverse repertoire. Furthermore, when T cells isolated from the WTVM chimeras were adoptively transferred to naïve Rag1-deficient 2º hosts, they trafficked to the lung and recruited neutrophils. Overall, these findings indicated that VM expression by radioresistant cells promoted the activation of autoreactive B cells and T cells that then differentiated into potentially pathogenic effector subsets.

Exposure and response prevention versus stress management training for adults and adolescents with obsessive compulsive disorder: A randomized clinical trial.

OBJECTIVE: Though exposure and response prevention (ERP) is a well-proven treatment for OCD across the lifespan, prior RCTs have not studied adolescent and adult patients with the same ERP protocol relative to an active comparator that controls for non-specific effects of treatment. This approach assesses differences in the effect of OCD-specific exposures in affected adolescents and adults and in response to ERP compared to a stress-management control therapy (SMT). METHODS: This assessor-blinded, parallel, 2-arm, randomized, ambulatory clinical superiority trial randomized adolescents (aged 12-18) and adults (24-46) with OCD (N = 126) to 12 weekly sessions of ERP or SMT. OCD severity was measured before, during and after treatment using the child or adult version of the Yale-Brown Obsessive Compulsive Scale (C/Y-BOCS), depending on participant age. We predicted that ERP would produce greater improvement in OCD symptoms than SMT and that there would be no significant post-treatment differences across age groups. RESULTS: ERP (n = 63) produced significantly greater improvements on C/Y-BOCS scores at post-treatment than SMT (n = 63) (Effect size = -0.72, CI = -0.52 to -0.91, p < .001). ERP also produced more treatment responders (ERP = 86%, SMT = 32%; χ2 = 46.37, p < .001) and remitters than SMT (ERP = 39%, SMT = 7%; χ2 = 16.14, p < .001). Finally, there were no statistically significant post-treatment differences in C/Y-BOCS scores between adolescents and adults assigned to ERP. CONCLUSION: A single ERP protocol is superior to SMT in treating both adolescents and adults with OCD. OCD-specific therapy is necessary across the lifespan for optimal outcomes in this highly disabling disorder, though non-specific treatments like SMT are still all-too-commonly provided.