Psychometric Properties of the PANS 31-Item Symptom Rating Scale.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS (N = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS (r = 0.81) and PANS Total and GIS (r = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.

A Mobile Application Adjunct to Augment Cognitive-Behavioral Group Therapy for Adolescents with Social Anxiety: Feasibility and Acceptability Results from the Wiring Adolescents with Social Anxiety via Behavioral Interventions Pilot Trial.

Objective: Cognitive-Behavioral Group Therapy (CBGT) is an established treatment for Social Anxiety (SA). However, diagnostic recovery rate is only 20.5% in CBGT, and up to 50% of patients remain symptomatic posttreatment. Using videocalls to deliver digital CBGT (dCBGT) is feasible, cost-effective, and efficacious. Yet, the impact of dCBGT on social functioning remains limited, as dCBGT does not offer opportunities for monitoring cognition and behavior in social situations. Wiring Adolescents with Social Anxiety via Behavioral Interventions (WASABI), a clinician-assisted application that uses ecological momentary assessments (EMAs), cognitive bias tests, and clinical self-reports, was investigated as an adjunct to dCBGT. Methods: A prospective, parallel arm, double-blind randomized controlled trial was employed in 24 SA adolescents randomly assigned to dCBGT versus dCBGT plus WASABI. Results: Study completion rates (83%) and exit survey data indicated that WASABI is feasible and acceptable. Engagement with EMAs varied from four to 244 EMAs completed per person. Cognitive bias tests and clinical self-reports were completed at least weekly by 53% and 69% of participants, respectively. While standard tests did not reveal statistically significant differences between dCBGT plus WASABI and dCBGT alone, effect sizes were greater for dCBGT plus WASABI on symptom severity, social skills, and functioning. Conclusions: Despite the small sample, preliminary results suggest that WASABI is feasible, acceptable, and may be an effective augmentation tool for treating SA in teenagers.

Predictors and Prospective Course of PANS: A Pilot Study Using Electronic Platforms for Data Collection.

Objectives: Little is known about the longitudinal course of pediatric acute-onset neuropsychiatric syndrome (PANS) because existing literature is primarily cross-sectional. To begin to address this gap, two digital platforms were used to prospectively monitor neuropsychiatric symptoms in children with PANS. The aim was to identify baseline clinical characteristics that would predict the course of neuropsychiatric symptoms over 12 weeks. We compared relative compliance between two electronic data acquisition platforms and evaluated agreement between parent-child ratings of symptoms. Methods: For 12 weeks, 20 children with PANS and their parents completed weekly rating scales of neuropsychiatric symptoms on Research Electronic Data Capture (REDCap) and concurrently parents completed tri-weekly ratings on My Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Chart, a symptom monitoring website. Longitudinal data were analyzed by using regression analyses. Results: Greater duration of time between onset of PANS and study enrollment was associated with worsening of parent-rated neuropsychiatric symptoms over 12 weeks (p = 0.05). Higher scores on parents' Caregiver Burden Inventory at baseline predicted that children would report more severe symptoms over the 12-week period (p = 0.01). Compliance rates for parents were 86.3% for the weekly REDCap PANS Symptoms Rating Scale compared with 53.8% for the tri-weekly My PANDAS Chart ratings. There was moderate agreement between children and parents on the PANS Symptom Rating Scale (r = 0.55, p < 0.0001). Conclusion: Our study highlights the utility of electronic methods for tracking longitudinal symptoms in children with PANS and suggests that particular baseline characteristics (e.g., delay in identification and treatment of PANS, greater caregiver burden) may be indicative of a differential trajectory of PANS course, with more severe symptoms over the short term. clinicaltrials.gov NCT04382716.

Sub-graph entropy based network approaches for classifying adolescent obsessive-compulsive disorder from resting-state functional MRI.

This paper presents a novel approach for classifying obsessive-compulsive disorder (OCD) in adolescents from resting-state fMRI data. Currently, the state-of-the-art for diagnosing OCD in youth involves interviews with adolescent patients and their parents by an experienced clinician, symptom rating scales based on Diagnostic and Statistical Manual of Mental Disorders (DSM), and behavioral observation. Discovering signal processing and network-based biomarkers from functional magnetic resonance imaging (fMRI) scans of patients has the potential to assist clinicians in their diagnostic assessments of adolescents suffering from OCD. This paper investigates the clinical diagnostic utility of a set of univariate, bivariate and multivariate features extracted from resting-state fMRI using an information-theoretic approach in 15 adolescents with OCD and 13 matched healthy controls. Results indicate that an information-theoretic approach based on sub-graph entropy is capable of classifying OCD vs. healthy subjects with high accuracy. Mean time-series were extracted from 85 brain regions and were used to calculate Shannon wavelet entropy, Pearson correlation matrix, network features and sub-graph entropy. In addition, two special cases of sub-graph entropy, namely node and edge entropy, were investigated to identify important brain regions and edges from OCD patients. A leave-one-out cross-validation method was used for the final predictor performance. The proposed methodology using differential sub-graph (edge) entropy achieved an accuracy of 0.89 with specificity 1 and sensitivity 0.80 using leave-one-out cross-validation with in-fold feature ranking and selection. The high classification accuracy indicates the predictive power of the sub-network as well as edge entropy metric.

Sertraline Effects on Striatal Resting-State Functional Connectivity in Youth With Obsessive-Compulsive Disorder: A Pilot Study.

OBJECTIVE: Foundational knowledge on neural circuitry underlying pediatric obsessive-compulsive disorder (OCD) and how it changes during standard treatment is needed to provide the basis for conceptualization and development of novel targeted treatments. This study explored the effects of sertraline, a selective serotonin reuptake inhibitor, on resting-state functional connectivity in cortico-striatal-thalamic-cortical circuits in pediatric OCD. METHOD: Medication-free youths with OCD (n = 14) and healthy controls (n = 14) were examined at baseline and 12 weeks with resting-state functional magnetic resonance imaging. Between scan sessions, participants with OCD received 12 weeks of sertraline. For each scan, seed-based whole-brain resting-state functional connectivity analyses were conducted with 6 striatal seeds. Analysis of variance examined the interaction between group and time on striatal connectivity, including cluster-based thresholding to correct for multiple tests. Connectivity changes within circuits identified in group analyses were correlated with clinical change. RESULTS: Two significant group-by-time effects in the OCD group showed increased striatal connectivity from baseline to 12 weeks compared with controls. Circuits demonstrating this pattern included the right putamen with the left frontal cortex and insula and the left putamen with the left frontal cortex and pre- and post-central cortices. Increase in connectivity in the left putamen circuit was significantly correlated with clinical improvement on the Children's Yale-Brown Obsessive-Compulsive Scale score (r = -0.58, p = .03). CONCLUSION: Sertraline appears to affect specific striatal-based circuits in pediatric OCD, and these changes in part could account for clinical improvement. Future work is needed to confirm these preliminary findings, which would facilitate identification of circuit-based targets for novel treatment development. CLINICAL TRIAL REGISTRATION INFORMATION: Effects of Sertraline on Brain Connectivity in Adolescents with OCD; https://clinicaltrials.gov/; NCT02797808.

Use of Computer Vision Tools to Identify Behavioral Markers of Pediatric Obsessive-Compulsive Disorder: A Pilot Study.

OBJECTIVES: The clinical presentation of pediatric obsessive-compulsive disorder (OCD) is heterogeneous, which is a stumbling block to understanding pathophysiology and to developing new treatments. A major shift in psychiatry, embodied in the Research Domain Criteria (RDoC) initiative of National Institute of Mental Health, recognizes the pitfalls of categorizing mental illnesses using diagnostic criteria. Instead, RDoC encourages researchers to use a dimensional approach, focusing on narrower domains of psychopathology to characterize brain-behavior relationships. Our aim in this multidisciplinary pilot study was to use computer vision tools to record OCD behaviors and to cross-validate these behavioral markers with standard clinical measures. METHODS: Eighteen youths with OCD and 21 healthy controls completed tasks in an innovation laboratory (free arrangement of objects, hand washing, arrangement of objects on contrasting carpets). Tasks were video-recorded. Videos were coded by blind raters for OCD-related behaviors. Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and other scales were administered. We compared video-recorded measures of behavior in OCD versus healthy controls and correlated video measures and clinical measures of OCD. RESULTS: Behavioral measures on the videos were significantly correlated with specific CY-BOCS dimension scores. During the free arrangement task, more time spent ordering objects and more moves of objects were both significantly associated with higher CY-BOCS ordering/repeating dimension scores. Longer duration of hand washing was significantly correlated with higher scores on CY-BOCS ordering/repeating and forbidden thoughts dimensions. During arrangement of objects on contrasting carpets, more moves and more adjustment of objects were significantly associated with higher CY-BOCS ordering/repeating dimension scores. CONCLUSION: Preliminary data suggest that measurement of behavior using video recording is a valid approach for quantifying OCD psychopathology. This methodology could serve as a new tool for investigating OCD using an RDoC approach. This objective, novel behavioral measurement technique may benefit both researchers and clinicians in assessing pediatric OCD and in identifying new behavioral markers of OCD. Clinical Trial Registry: Development of an Instrument That Monitors Behaviors Associated With OCD. NCT02866422. http://clinicaltrials.gov.

Treating child and adolescent anxiety effectively: Overview of systematic reviews.

We conducted an overview of systematic reviews about child and adolescent anxiety treatment options (psychosocial; medication; combination; web/computer-based treatment) to support evidence informed decision-making. Three questions were addressed: (i) Is the treatment more effective than passive controls? (ii) Is there evidence that the treatment is superior to or non-inferior to (i.e., as good as) active controls? (iii) What is the quality of evidence for the treatment? Pre-specified inclusion criteria identified high quality systematic reviews (2000-2015) reporting treatment effects on anxiety diagnosis and symptom severity. Evidence quality (EQ) was rated using Oxford evidence levels [EQ1 (highest); EQ5 (lowest)]. Twenty-two of 39 eligible reviews were high quality (AMSTAR score≥3/5). CBT (individual or group, with or without parents) was more effective than passive controls (EQ1). CBT effects compared to active controls were mixed (EQ1). SSRI/SNRI were more effective than placebo (EQ1) but comparative effectiveness remains uncertain. EQ for combination therapy could not be determined. RCTs of web/computer-based interventions showed mixed results (EQ1). CBM/ABM was not more efficacious than active controls (EQ1). No other interventions could be rated. High quality RCTs support treatment with CBT and medication. Findings for combination and web/computer-based treatment are encouraging but further RCTs are required. Head-to-head comparisons of active treatment options are needed.

Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder.

Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed.

School-Based Interventions for Anxious Children: Long-Term Follow-Up.

This study examined the long-term outcomes of a nonclinical sample of anxious children (N = 61) who were randomized by school to 9 weeks of group cognitive-behavioral therapy (CBT) for children, group CBT for children plus parent training, or no-treatment control. Parents and children completed measures of anxiety symptoms at baseline, posttreatment, and at 3-, 6-, 12-month, 2-, and 3-year posttreatment follow-ups. Piecewise longitudinal growth curve analyses were applied to the data. When the two CBT groups were combined and compared with control, the combined treatment group showed significantly greater reduction in children's anxiety severity based on the parent ratings in the first longitudinal phase. However, on the parent Clinician Severity Rating, gains were maintained to 3 years. Child report revealed no significant differences between groups on anxiety reduction. This study maintained a small no-treatment control group during the entire follow-up period. From parental perspective only, school-based group CBT appeared to be beneficial in decreasing severity of anxiety symptoms and maintaining gains over time.

Classification of obsessive-compulsive disorder from resting-state fMRI.

Obssesive-compulsive disorder (OCD) is a serious mental illness that affects the overall quality of the patients' daily lives. Accurate diagnosis of this disorder is a primary step towards effective treatment. Diagnosing OCD is a lengthy procedure that involves interviews, symptom rating scales and behavioral observation as well as the experience of a clinician. Discovering signal processing and network based biomarkers from functional magnetic resonance scans of patients may greatly assist the clinicians in their diagnostic assessments. In this paper, we explore the use of Pearson's correlation scores and network based features to predict if a subject has OCD. We extracted mean time series from 112 brain regions and decomposed them to 5-frequency bands. The mean time courses were used to calculate the Pearson's correlation matrix and network based features for each band. Minimum redundancy maximum relevance feature selection method is applied to the Pearson's correlation matrix and network based features from each frequency band to select the best features for the final predictor. A leave-one-out cross validation method is used for the final predictor performance. Our proposed methodology achieves 80% accuracy (23 out of 29 subjects classified correctly) with 81% sensitivity(13 out of 16 OCD subjects identified correctly) and 77% specificity (10 out of 13 controls identified correctly) using leave-one-out with in-fold feature ranking and selection. The most discriminating feature bands are 0.06-0.11 Hz for Pearson's correlation and 0.03-0.06 Hz for network based features. The high classification accuracy indicates the predictive power of the network features as well as carefully chosen Pearson's correlation values.

PREVENTING CHILD AND ADOLESCENT ANXIETY DISORDERS: OVERVIEW OF SYSTEMATIC REVIEWS.

Overviews of systematic reviews (OSRs) provide rapid access to high quality, consolidated research evidence about prevention intervention options, supporting evidence-informed decision-making, and the identification of fruitful areas of new research. This OSR addressed three questions about prevention strategies for child and adolescent anxiety: (1) Does the intervention prevent anxiety diagnosis and/or reduce anxiety symptoms compared to passive controls? (2) Is the intervention equal to or more effective than active controls? (3) What is the evidence quality (EQ) for the intervention? Prespecified inclusion criteria identified systematic reviews and meta-analyses (2000-2014) with an AMSTAR quality score ≥ 3/5. EQ was rated using Oxford evidence levels EQ1 (highest) to EQ5 (lowest). Three reviews met inclusion criteria. One narrative systematic review concluded school-based interventions reduce anxiety symptoms. One meta-analysis pooled 65 randomized controlled trials (RCTs; any intervention) and reported a small, statistically significant reduction in anxiety symptoms and diagnosis incidence. Neither review provided pooled effect size estimates for specific intervention options defined by type (i.e., universal/selective/indicated), intervention content, or comparison group (i.e., passive/active control), thus precluding EQ ratings. One meta-analysis pooled trials of vigorous exercise and reported small, nonstatistically significant reductions in anxiety symptoms for comparisons against passive and active controls (EQ1). Better use of primary studies in meta-analyses, including program-specific pooled effect size estimates and network meta-analysis is needed to guide evidence-informed anxiety prevention program choices. RCTs of innovative community/primary care based interventions and web-based strategies can fill knowledge gaps.

Treating individuals with social anxiety disorder and at-risk drinking: phasing in a brief alcohol intervention following paroxetine.

Paroxetine alone is not sufficient to decrease alcohol use in socially anxious alcoholics seeking anxiety treatment. We tested the hypothesis that adding a brief-alcohol-intervention (BI) to paroxetine would decrease alcohol use. All subjects (N=83) had a diagnosis of social anxiety disorder, endorsed drinking to cope with anxiety, were NIAAA-defined at-risk drinkers, and were randomized to either paroxetine alone, or paroxetine plus BI. Both groups showed significant improvement in both social anxiety severity (F(5,83)=61.5, p<0.0001) and drinking to cope (e.g. F(4,79)=23, p<0.0001) and these two constructs correlated with each other (B=3.39, SE=0.696, t(71)=4.88, p<0.001). BI was not effective at decreasing alcohol use (e.g. no main effect of group, all p values >0.3). Paroxetine decreased social anxiety severity in the face of heavy drinking and decreasing the anxiety was related to a concurrent decrease in coping related drinking. BI was not effective at decreasing drinking or drinking to cope.

Panic disorder and school refusal.

This article provides clinical and research information about panic disorder, agoraphobia, and school refusal. Proposed changes to the definition of panic disorder and agoraphobia for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition are outlined. Treatment of panic disorder, and school refusal in children and adolescents is also discussed.

Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and childhood obsessive-compulsive disorder.

OBJECTIVE: The objectives of this study were to identify unique clinical characteristics of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) compared with a control group of children with non-PANDAS obsessive-compulsive disorder (OCD) with respect to ancillary symptoms, types of obsessions and compulsions, symptom severity, and co-morbid DSM-IV diagnoses. METHOD: Classification of PANDAS was based on review of pediatric and psychiatric records using the criteria developed by Swedo and colleagues. Children aged 6-14 with PANDAS (n = 21) and non-PANDAS OCD (n = 18) were assessed by blind independent evaluators using the PANDAS Questionnaire, Children's Yale-Brown Obsessive Compulsive Scale, Yale Global Tic Severity Scale, and Anxiety Disorders Interview Schedule for DSM-IV. RESULTS: PANDAS children were significantly more likely to present with separation anxiety, urinary urgency, hyperactivity, impulsivity, deterioration in handwriting, and decline in school performance during their initial episode of neuropsychiatric illness compared with children with OCD. Total tics and vocal tics were more severe in PANDAS children. Separation anxiety disorder and social phobia were more prevalent in non-PANDAS OCD children. Children with non-PANDAS OCD were significantly more likely to include others in their rituals. There were no significant differences between groups on demographics or severity of OCD. CONCLUSIONS: Distinguishing clinical characteristics in PANDAS, which included urinary urgency, hyperactivity, impulsivity, and deterioration in handwriting, are linked to basal ganglia functions. These clinical characteristics will aid in the differentiation of PANDAS children for research and clinical purposes and ultimately advance our understanding and treatment of this disorder.

Anxiety disorders and posttraumatic stress disorder update.

Anxiety disorders are one of the most common categories of psychopathology in children and adolescents. This article provides an overview of several anxiety disorders that are diagnosed often during childhood and adolescence, including separation anxiety disorder, generalized anxiety disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder. Although anxiety disorders commonly show similar clinical characteristics during childhood and adulthood, this article highlights some of the differences that may present across the life span.

Generalized anxiety disorder in a nonclinical sample of children: symptom presentation and predictors of impairment.

Presentation of generalized anxiety disorder (GAD) in a nonclinical sample of children (7-11 years old) and factors that predict overall impairment were examined. Symptom presentation was compared in children with GAD (n=49) and anxious children without GAD (n=42). Children with GAD endorsed significantly more worries, greater intensity of worries, and more DSM-IV associated symptoms than anxious children without GAD. Eighty-six percent of children with GAD had a comorbid diagnosis with 4% having a depressive disorder. Number of associated symptoms was most predictive of GAD impairment based on child perspective and intensity of worry was most predictive based on clinician perspective. Overall, findings from the current study are consistent with reports based on clinical samples. The DSM-IV-TR criteria for GAD were supported, with the exception that children with GAD typically present with several associated symptoms, rather than only one.

School-based interventions for anxious children: 3-, 6-, and 12-month follow-ups.

OBJECTIVE: To follow 61 participants (7-11 years old) from a study that compared three school-based interventions for anxious children: group cognitive-behavioral therapy (CBT) for children, group CBT for children plus parent training, and no-treatment control to determine whether posttreatment benefits are sustained longitudinally. METHOD: Parent, child, and clinician report measures of child anxiety were completed at 3, 6, and 12 months posttreatment. Semistructured diagnostic interviews were administered at 6- and 12-month follow-ups. For initial analyses, the group CBT and group CBT plus parent training conditions were collapsed into one group and compared to control. When significant results were found, each active treatment group was compared to control. RESULTS: Across several measures, the collapsed CBT group sustained significant improvement in anxiety severity and impairment across a 12-month period compared to control. There were no significant differences between the three groups on remission of baseline anxiety disorders or incidence of new anxiety disorders during the follow-up. Several parent-report measures at 3 and 6 months posttreatment suggested that group CBT for children plus parent training provided additional benefit over the group CBT for children when each was compared to the control group. CONCLUSIONS: School-based CBT appears effective in decreasing anxiety symptoms up to 12 months posttreatment for anxious children.

Symptom presentation and classroom functioning in a nonclinical sample of children with social phobia.

This study investigates symptom presentation and school functioning in a nonclinical sample of children with social phobia (SP). Forty-five children with SP were identified via school-wide screenings and follow-up diagnostic interviews. Analyses examined types and intensity of fears, number of social situations avoided, interpersonal relationships, and classroom functioning. To identify characteristics unique to social phobic children, children with SP (n = 45) were compared to anxious children without SP (n = 56) on the above variables. Comorbidity in children with SP and factors associated with SP severity were also evaluated. Compared to anxious children without SP, children with SP feared and avoided a significantly greater number of social situations. In addition, they were significantly more likely to have trouble with making friends and to prefer being alone rather than with peers. All children with SP met criteria for at least one comorbid disorder. Significant factors explaining child-reported severity of SP were number of social situations avoided and intensity of fears. Greater severity of SP was significantly associated with poorer social skills, poorer leadership skills, greater attention difficulties, and greater learning problems in the classroom. It is important to understand the symptom presentation of SP so that children with SP are identified early and effective interventions are instituted. This is especially critical given the impact of SP on school functioning.

Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders.

This revised practice parameter reviews the evidence from research and clinical experience and highlights significant advancements in the assessment and treatment of anxiety disorders since the previous parameter was published. It highlights the importance of early assessment and intervention, gathering information from various sources, assessment of comorbid disorders, and evaluation of severity and impairment. It presents evidence to support treatment with psychotherapy, medications, and a combination of interventions in a multimodal approach.