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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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Practice parameters recommend systematic assessment of depression symptoms over the course of treatment to inform treatment planning; however, there are currently no guidelines regarding how to use symptom monitoring to guide treatment decisions for psychotherapy. The current study compared two time points (week 4 and week 8) for assessing symptoms during interpersonal psychotherapy for depressed adolescents (IPT-A) and explored four algorithms that use the symptom assessments to select the subsequent treatment., Method: Forty adolescents (aged 12-17 years) with a depression diagnosis began IPT-A with an initial treatment plan of 12 sessions delivered over 16 weeks. Adolescents were randomized to a week 4 or week 8 decision point for considering a change in treatment. Insufficient responders at either time point were randomized a second time to increased frequency of IPT-A (twice per week) or addition of fluoxetine. Measures were administered at baseline and weeks 4, 8, 12, and 16., Results: The week 4 decision point for assessing response and implementing treatment augmentation for insufficient responders was more efficacious for reducing depression symptoms than the week 8 decision point. There were significant differences between algorithms in depression and psychosocial functioning outcomes., Conclusion: Therapists implementing IPT-A should routinely monitor depression symptoms and consider augmenting treatment for insufficient responders as early as week 4 of treatment., Clinical Trial Registration Information: An Adaptive Treatment Strategy for Adolescent Depression. https://clinicaltrials.gov; NCT02017535., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

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.

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.

This study examines relations between family functioning, parenting stress, parental psychopathology, and treatment outcome. Participants included 61 children (ages 7-11 years) with features or diagnoses of separation anxiety disorder, generalized anxiety disorder, and/or social phobia. Treatment conditions included group cognitive behavioral therapy (CBT) and no-treatment control. Higher family cohesion at baseline was associated with significantly greater decreases in child anxiety at posttreatment for participants who received CBT, while no association was found for the no-treatment control participants. Parenting stress and parental psychopathology were not associated with treatment outcome for either condition. Post hoc analyses examining relations between family cohesion, parenting stress, and parental psychopathology showed that parents from families low in cohesion reported significantly higher levels of parenting stress and psychopathology compared to parents from families high in cohesion. These results will facilitate development and implementation of effective interventions with anxious children.

Objective: To compare the effectiveness of three school-based interventions for anxious children: group cognitive-behavioral therapy (CBT) for children, group CBT for children plus parent training group, and no-treatment control., Method: Students (7-11 years old) in three elementary schools (N = 453) were screened using the Multidimensional Anxiety Scale for Children and teacher nomination. Subsequently, 101 identified children and their parents completed the Anxiety Disorders Interview Schedule for DSM-IV, Child Version. Children with features or DSM-IV diagnoses of separation anxiety disorder, generalized anxiety disorder, and/or social phobia (n = 61) were randomized by school to one of three conditions. Active treatments were nine weekly sessions of either group CBT or group CBT plus concurrent parent training., Results: Clinician-report, child-report, and parent-report measures of child anxiety demonstrated significant benefits of CBT treatments over the no-treatment control group. Effect size was 0.58 for change in composite clinician severity rating, the primary outcome measure, favoring collapsed CBT conditions compared with control. In addition, several instruments showed significantly greater improvement in child anxiety for group CBT plus parent training over group CBT alone., Conclusions: Both active CBT treatments were more effective than the no-treatment control condition in decreasing child anxiety symptoms and associated impairment. When parent training was combined with child group CBT, there were some additional benefits for the children.

The present study examined the relation between maternal anxiety symptoms and child anxiety symptoms and evaluated whether a reporting bias is associated with maternal anxiety. Fifty-seven mother-child pairs participated. All children had features or diagnoses of separation anxiety disorder (SAD), generalized anxiety disorder, and/or social phobia. Measures of maternal symptomatology and child anxiety were administered. Higher levels of maternal phobic anxiety on the Brief Symptom Inventory were significantly associated with higher levels of separation anxiety in children. After controlling for clinician rating of SAD severity, maternal phobic anxiety emerged as a significant predictor of maternal ratings of child separation anxiety, accounting for 19% of the variance. Phobic mothers endorsed levels of separation anxiety in their children that exceeded levels endorsed by clinicians, suggesting maternal overreporting.

Objective: To identify predictors of treatment response to 8 weeks of cognitive-behavioral therapy (CBT) among anxious-depressed adolescents with school refusal, half of whom received imipramine plus CBT and half of whom received placebo plus CBT., Method: A hierarchical multiple regression analysis was used to evaluate the following variables as potential predictors of treatment response as measured by school attendance at the end of treatment: baseline severity (school attendance at baseline), drug group (imipramine versus placebo), presence of separation anxiety disorder (SAD), and presence of avoidant disorder (AD)., Results: Baseline attendance, CBT plus imipramine, SAD, and AD were significant predictors of treatment response and accounted for 51% of the variance in outcome. Specifically, a higher rate of attendance at baseline and receiving imipramine predicted a better response to treatment whereas the presence of SAD and AD predicted a poorer response to treatment. The relationship between sociodemographic variables and treatment outcome was also evaluated. Age and socioeconomic status were unrelated to school attendance after treatment. Males had significantly higher rates of attendance after treatment than females., Conclusions: Adolescents with school refusal are a heterogeneous population and require individualized treatment planning. Variables such as diagnosis and severity at the start of treatment should be taken into consideration when planning treatment.

This study identifies and characterizes symptoms of caffeine dependence in adolescents. Thirty-six adolescents who consumed caffeine daily and had some features of caffeine dependence on telephone screen were scheduled for outpatient evaluation. Evaluation included the Diagnostic Interview Schedule for Children-IV-Youth Version (DISC-IV) and modified DISC-IV questions that assessed caffeine dependence based on DSM-IV substance dependence criteria. Of 36 subjects, 41.7% (n=15) reported tolerance to caffeine, 77.8% (n=28) described withdrawal symptoms after cessation or reduction of caffeine intake, 38.9% (n=14) reported desire or unsuccessful attempts to control use, and 16.7% (n=6) endorsed use despite knowledge of physical or psychological problems associated with caffeine. There was no significant difference in the amount of caffeine consumed daily by caffeine dependent versus non-dependent teenagers. These findings are important due to the vast number of adolescents who drink caffeinated beverages.