Efficacy and acceptability of cognitive-behavioral therapy and serotonin reuptake inhibitors for pediatric obsessive-compulsive disorder: a network meta-analysis.

BACKGROUND: Cognitive-behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) are recommended treatments for pediatric obsessive-compulsive disorder (OCD), but their relative efficacy and acceptability have not been comprehensively examined. Further, it remains unclear whether the efficacy of in-person CBT is conserved when delivered in other formats, such as over telephone/webcam or as Internet-delivered CBT (ICBT). METHODS: PubMed, PsycINFO, trial registries, and previous systematic reviews were searched for randomized controlled trials (RCTs) comparing CBT (in-person, webcam/telephone-delivered, or ICBT) or SRIs with control conditions or each other. Network meta-analyses were conducted to examine efficacy (post-treatment Children's Yale-Brown Obsessive Compulsive Scale) and acceptability (treatment discontinuation). Confidence in effect estimates was evaluated with CINeMA (Confidence in Network Meta-Analysis). RESULTS: Thirty eligible RCTs and 35 contrasts comprising 2,057 youth with OCD were identified. In-person CBT was significantly more efficacious than ICBT, waitlist, relaxation training, and pill placebo (MD range: 3.95-11.10; CINeMA estimate of confidence: moderate) but did not differ significantly from CBT delivered via webcam/telephone (MD: 0.85 [-2.51, 4.21]; moderate), SRIs (MD: 3.07 [-0.07, 6.20]; low), or the combination of in-person CBT and SRIs (MD: -1.20 [-5.29, 2.91]; low). SRIs were significantly more efficacious than pill placebo (MD: 4.59 [2.70, 6.48]; low) and waitlist (MD: 8.03 [4.24, 11.82]; moderate). No significant differences for acceptability emerged, but confidence in estimates was low. CONCLUSIONS: In-person CBT and SRIs produce clear benefits compared to waitlist and pill placebo and should be integral parts of the clinical management of pediatric OCD, with in-person CBT overall having a stronger evidence base. The combination of in-person CBT and SRIs may be most efficacious, but few studies hinder firm conclusions. The efficacy of CBT appears conserved when delivered via webcam/telephone, while more trials evaluating ICBT are needed.

A Family Genetic Study of Obsessive Compulsive Disorder in Youth.

OBJECTIVE: To use a family genetic study to evaluate familial risk of obsessive compulsive disorder (OCD) and common comorbid illnesses in first-degree relatives of pediatric-onset probands with primary OCD. METHOD: One hundred and thirty youth with OCD and their 133 siblings and 241 parents and 49 pediatric controls were directly evaluated along multiple domains including psychopathology using structured diagnostic interviews and clinical corroboration. RESULTS: Rates of anxiety, mood, disruptive behavior, and tic disorders were markedly elevated in the probands while rates in siblings were elevated at rates between the probands and controls. Twenty six percent of first-degree relatives had clinical OCD, 9% had chronic tics or Tourette's disorder, and 21% met criteria for ADHD. CONCLUSION: Rates of familial transmission of OCD and common comorbid illnesses were significantly higher in our pediatric-onset probands than rates reported in the literature in relatives of those with adult-onset OCD.

Promoting OCD WEllness and resilience (POWER) study: Rationale, design, and methods.

Obsessive-compulsive disorder (OCD) affects 1-2% of children and is associated with functional impairment and diminished quality of life. Several treatments are efficacious: cognitive behavioral therapy (CBT) with exposure and response prevention, serotonin reuptake inhibitor (SRI) monotherapy, and combined treatment (SRI + CBT). Expert clinician-informed practice parameters suggest that youth with mild to moderate OCD should be treated initially with CBT yet SRIs are frequently employed as the first-line intervention or in combination with psychotherapy in applied practice. Empirical data to guide SRI discontinuation in pediatric OCD are very limited. This study, Promoting OCD Wellness and Resiliency (POWER), aims to address this gap through a two phase, double-blinded, placebo-controlled, randomized controlled non-inferiority trial with the purpose of evaluating whether youth with OCD on an SRI can discontinue their medication after successful CBT augmentation and maintain wellness for a period of 24 weeks during which they receive maintenance CBT that models standard-of-care. In this paper we describe the rationale and methodological design of the POWER study.

Childhood Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) frequently affects children and adolescents, with most cases beginning during this time. Symptoms of OCD in youth may present as exaggerated developmental concerns and excessive ritualistic behavior beyond what is part of normal development, yet low levels of insight may prevent recognition. Affected youth commonly have comorbid neurodevelopmental diagnoses, especially males. Early detection and intervention are critical to recovery and remission, as well as family involvement in treatment. Cognitive behavioral therapy and serotonin reuptake inhibitors are first-line treatments.

An ultra-brief screening scale for pediatric obsessive-compulsive disorder: The OCI-CV-5.

BACKGROUND: Obsessive-compulsive disorder (OCD) is an often disabling and chronic condition that is normally assessed using diagnostic interviews or lengthy self-report questionnaires. This makes routine screening in general health settings impractical, and as a result OCD is often under-(or mis-)recognized. The present study reports on the development of an ultra-brief version of the Obsessive-Compulsive Inventory-Child Version (OCI-CV) which may be administered routinely as a screener for pediatric OCD. METHOD: A total of 489 youth diagnosed with OCD, 259 non-clinical controls, and 299 youth with other disorders completed the OCI-CV and other indices of psychopathology. Using item analyses, we extracted five items and examined the measure's factor structure, sensitivity and specificity, and convergent and discriminant validity. RESULTS: We extracted five items that assess different dimensions of OCD (washing, checking, ordering, obsessing, neutralizing/counting), termed the OCI-CV-5. Results revealed that the measure possesses good to excellent psychometric properties, and a cutoff off (≥2) yielded optimal sensitivity and specificity. LIMITATIONS: Participants were predominantly White. In addition, more research is needed to examine the OCI-CV-5's test-retest reliability and sensitivity to treatment. CONCLUSIONS: The OCI-CV-5 shows promise as an ultra-brief self-report screener for identifying OCD in youth when in-depth assessment is unfeasible.

Cognitive Beliefs Across the Symptom Dimensions of Pediatric Obsessive-Compulsive Disorder: Type of Symptom Matters.

The cognitive model of obsessive-compulsive disorder (OCD) posits that dysfunctional cognitive beliefs are crucial to the onset and maintenance of OCD; however, the relationship between these cognitive beliefs and the heterogeneity of OCD symptoms in children and adolescents remains unknown. We examined how the major belief domains of the cognitive model (inflated responsibility/threat estimation, perfectionism/intolerance of uncertainty, importance/control of thoughts) and dysfunctional metacognitions were related to OCD symptoms across the following dimensions: doubting/checking, obsessing, hoarding, washing, ordering, and neutralization. Self-report ratings from 137 treatment-seeking youth with OCD were analyzed. When cognitive beliefs and symptom dimensions were analyzed in tandem, inflated responsibility/threat estimation and dysfunctional metacognitions were uniquely related to doubting/checking, obsessing, and hoarding and perfectionism/intolerance of uncertainty to ordering. Cognitive beliefs explained a large proportion of variation in doubting/checking (61%) and obsessing (46%), but much less so in ordering (15%), hoarding (14%), neutralization (8%), and washing (3%). Similar relations between cognitive beliefs and symptom dimensions were present in children and adolescents. Cognitive beliefs appear to be relevant for pediatric OCD related to harm, responsibility, and checking, but they do not map clearly onto contamination and symmetry-related symptoms. Implications for OCD etiology and treatment are discussed.

The OCI-CV-R: A Revision of the Obsessive-Compulsive Inventory - Child Version.

BACKGROUND: The Obsessive-Compulsive Inventory-Children's Version (OCI-CV) was developed to assess obsessive-compulsive symptoms in youth. Recent changes in the Diagnostic and Statistical Manual (DSM-5) exclude hoarding from inclusion in the diagnosis of obsessive-compulsive disorder (OCD). Accordingly, the present study examined the reliability, validity, factorial structure, and diagnostic sensitivity of a revised version of the scale - the OCI-CV-R- that excludes items assessing hoarding. METHODS: Participant were 1047 youth, including 489 meeting DSM criteria for primary OCD, 298 clinical controls, and 260 nonclinical controls, who completed the OCI-CV and measures of obsessive-compulsive symptom severity, depression, and anxiety at various treatment and research centers. RESULTS: Findings support a five-factor structure (doubting/checking, obsessing, washing, ordering, and neutralizing), with a higher order factor. Factorial invariance was found for older (12-17 years) and younger (7-11 years) children. Internal consistency of the OCI-CV-R was acceptable, and discriminant and convergent validity were adequate and akin to that of its progenitor. Diagnostic sensitivity and specificity were found for a total score of 8 and higher. CONCLUSION: It is recommended that the OCI-CV-R replace the former version, and that this measure serve as part of a comprehensive clinical assessment of youth with OCD. Recommendations for further research with ethnically and racially diverse samples, as well as the need to establish benchmark scores are discussed.

Towards a definitive symptom structure of obsessive-compulsive disorder: a factor and network analysis of 87 distinct symptoms in 1366 individuals.

BACKGROUND: The symptoms of obsessive-compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques. METHODS: A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive-Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the resulting dimensions were established using network analysis. Associations between dimensions and sociodemographic and clinical variables were explored using structural equation modeling (SEM). RESULTS: Thirteen first-order symptom dimensions emerged that could be parsimoniously reduced to eight broad dimensions, which were valid across the lifespan: Disturbing Thoughts, Incompleteness, Contamination, Hoarding, Transformation, Body Focus, Superstition, and Loss/Separation. A general OCD factor could be included in the final factor model without a significant decline in model fit according to most fit indices. Network analysis showed that Incompleteness and Disturbing Thoughts were most central (i.e. had most unique interconnections with other dimensions). SEM showed that the eight broad dimensions were differentially related to sociodemographic and clinical variables. CONCLUSIONS: Future research will need to establish if this expanded hierarchical and multidimensional model can help improve our understanding of the etiology, neurobiology and treatment of OCD.

Systematic Review and Meta-analysis: An Empirical Approach to Defining Treatment Response and Remission in Pediatric Obsessive-Compulsive Disorder.

OBJECTIVE: A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. METHOD: A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N = 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. RESULTS: The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7-84.1; specificity = 81.7, 95% CI = 81.5-81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8-82.2; specificity = 84.6, 95% CI = 84.4-84.8). CONCLUSION: Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD.

Longitudinal trajectory and predictors of change in family accommodation during exposure therapy for pediatric OCD.

Family accommodation (FA) is key in the maintenance of OCD. However, most studies are cross-sectional, and have not identified long-term trajectories and correlates of FA changes over treatment. This study investigated changes in clinician-rated FA over 10 sessions of cognitive behavioral therapy (CBT) for 142 children with OCD, as well as several key predictors/correlates: (a) clinician-rated OCD symptom severity, (b) child- and parent-rated functional impairment, (c) parent-rated treatment expectancies, and (d) child- and parent-rated therapeutic alliance. Multi-level models indicated that FA changed significantly during treatment, with gains maintained over 6-months. Baseline clinician-rated OCD severity did not predict changes in FA. Significant interactions indicated that children with higher child- and parent-rated impairment exhibited greater FA improvements over treatment (versus children with lower impairment). Child- and parent-rated therapeutic alliance and parent-rated expectancies did not predict FA changes. Finally, FA mediated the relationship between OCD severity and parent- (but not child-) rated impairment. Reverse mediation models were also significant. Findings indicate that CBT can successfully reduce FA (a) even if children experience high OCD severity and interference in school, relationships, and family life, and (b) regardless of non-specific factors like treatment expectancies and alliance. FA reductions are an important mechanism mediating treatment response.

Developmental Considerations in Obsessive Compulsive Disorder: Comparing Pediatric and Adult-Onset Cases.

There appear to be two peaks of incidence of Obsessive Compulsive Disorder (OCD), one with a pre-adolescent onset and another in early adulthood. As new cases are added, the cumulative prevalence of OCD increases, but the great majority of cases have an onset in youth. The notion that early onset OCD represents a unique developmental subtype of the disorder has been considered by many researchers based on several specific age-related factors. Ascertainment and early intervention in affected youth is critical to abbreviate the functional impairments associated with untreated illness. In this paper we review the clinical, familial and translational biomarker correlates seen in early onset OCD that support the notion of a developmental subtype and discuss implications for research and treatment aimed at this cohort. The importance of cognitive, academic and social development tasks of childhood and adolescence, illness-specific and familial factors, and immune-mediated inflammatory factors are discussed, with their implications for management.

Exome sequencing in obsessive-compulsive disorder reveals a burden of rare damaging coding variants.

Obsessive-compulsive disorder (OCD) affects 1-2% of the population, and, as with other complex neuropsychiatric disorders, it is thought that rare variation contributes to its genetic risk. In this study, we performed exome sequencing in the largest OCD cohort to date (1,313 total cases, consisting of 587 trios, 41 quartets and 644 singletons of affected individuals) and describe contributions to disease risk from rare damaging coding variants. In case-control analyses (n = 1,263/11,580), the most significant single-gene result was observed in SLITRK5 (odds ratio (OR) = 8.8, 95% confidence interval 3.4-22.5, P = 2.3 × 10-6). Across the exome, there was an excess of loss of function (LoF) variation specifically within genes that are LoF-intolerant (OR = 1.33, P = 0.01). In an analysis of trios, we observed an excess of de novo missense predicted damaging variants relative to controls (OR = 1.22, P = 0.02), alongside an excess of de novo LoF mutations in LoF-intolerant genes (OR = 2.55, P = 7.33 × 10-3). These data support a contribution of rare coding variants to OCD genetic risk.

Irritability in Children and Adolescents With OCD.

Irritability is a common, impairing transdiagnostic symptom in childhood psychopathology, though it has not been comprehensively studied in pediatric obsessive-compulsive disorder (OCD). Further, the central cognitive behavioral treatment component for OCD, exposure and response prevention therapy (ERP), has been recently proposed as a treatment for irritability. This study aimed to evaluate whether certain clinical characteristics are associated with irritability in pediatric OCD and whether irritability reduces following ERP. Participants were 161 youth (ages 7-17) with OCD and a caregiver participating in a randomized controlled trial of D-cycloserine or pill placebo augmented ERP. Participants completed validated assessments during treatment. Irritability was significantly and positively associated with depressive symptoms, defiance, functional impairment, and family accommodation, but was not associated with pretreatment OCD severity, symptom dimensions, obsessive beliefs. Irritability significantly declined following treatment, with over half of youth with any pretreatment irritability experiencing clinically significant change, though this change was not related to OCD improvement. Results suggest that irritability may be a marker of psychiatric comorbidity, parental accommodation, and impairment in youth with OCD. Implications for the exposure-based treatment of irritability are discussed.

Neurocognitive endophenotypes in pediatric OCD probands, their unaffected parents and siblings.

BACKGROUND: Limited extant research on neurocognitive endophenotypes in obsessive-compulsive disorder (OCD) show inconsistent results. Limitations of this body of literature include small sample sizes, strict exclusion criteria, lack of objective standard normalized test scores, and significant lack of studies utilizing pediatric probands. This study aimed to address these limitations. METHODS: A large carefully screened cohort of pediatric OCD (n = 102), their unaffected siblings (n = 78), and parents (n = 164), completed a neuropsychological battery. To compare participants at different ages and developmental stages, standard scores were computed using test norms. Cluster-robust regression with sample size-adjusted sandwich estimates of variance, and interclass correlations were computed. False Discovery Rate procedures were employed to correct for multiplicity. RESULTS: Probands, siblings and parents demonstrated deficient task performance (Z < -0.5) on the 'number of trials to complete first category' on the Wisconsin Card Sorting Test, and on the Stroop color naming trials. Compared to test norms, the three groups exhibited medium to large effect sizes on these outcome measures. No other meaningful familial trends were found. CONCLUSIONS: OCD probands, their unaffected siblings and parents exhibited deficiencies in specific subdomains of cognitive flexibility and inhibitory control, namely, initial concept formation and proactive control, which may be valid candidate neurocognitive endophenotypes of OCD. No other meaningful familial effect has been found on other functions, including other executive function indices such as perseverations and interference control. These results highlight the need to carefully examine individual outcomes from executive function tests instead of the tendency to focus largely on major outcome measures.

Temporal precedence of the change in obsessive-compulsive symptoms and change in depressive symptoms during exposure and response prevention for pediatric obsessive-compulsive disorders.

The current study examined the temporal precedence of change in obsessive-compulsive symptoms and change in depressive symptoms during the course of an Exposure and Response Prevention (ERP) for pediatric OCD. Participants included 142 children and adolescents (7-17 years; mean age = 12.39, SD = 2.92; 51.40% female; 60.40% Non-Hispanic White) with a primary or co-primary diagnosis of OCD who received ERP in a two-site randomized controlled trial on d-cycloserine augmentation of CBT for pediatric OCD. Participants completed clinician-administered assessments of OC symptoms (Children's Yale-Brown Obsessive Compulsive Scale) and depressive symptoms (Children's Depression Rating Scale-Revised) from baseline to post-treatment follow-up. Lagged mediational analyses did not yield evidence in support of a mediating role for the change in OC symptoms in the effect of ERP on the change in depressive symptoms. In contrast, change in depressive symptoms mediated the effect of ERP treatment on the subsequent change in OC symptoms (95% confidence interval for indirect effect = -0.04 to -0.001), though the effect size was small. Controlling for the prior levels of the depressive symptoms this indirect effect became non-significant. Theoretical and clinical implications of the findings for the youth with OCD and comorbid depression are discussed.

When Science Challenges Our Long-Held Assumptions About the Robustness of Evidence for Standard of Care.

In this issue of the Journal, we publish two letters pertaining to the article "Systematic Review and Meta-analysis: Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder in Children and Adolescents" by Uhre et al.1 Their protocol employed the Cochrane Handbook for Systematic Reviews of Interventions to evaluate risk of bias (selection, performance, detection, attrition, and reporting biases) in the included 25 trials, contacting trial authors to obtain missing data where possible. They controlled for random errors owing to sparse data or multiple testing using Trial Sequential Analysis and evaluated the certainty of the evidence using the Grading of Recommendations Assessment Development and Evaluation approach. They concluded that cognitive-behavioral therapy (CBT) (versus no intervention) is effective for pediatric obsessive-compulsive disorder (OCD), but that the certainty of evidence was low or very low for all outcomes and that moderator analyses could often not be completed for lack of data. The authors made the point that blinding is always possible, even in CBT trials.

Clinical advances in obsessive-compulsive disorder: a position statement by the International College of Obsessive-Compulsive Spectrum Disorders.

In this position statement, developed by The International College of Obsessive-Compulsive Spectrum Disorders, a group of international experts responds to recent developments in the evidence-based management of obsessive-compulsive disorder (OCD). The article presents those selected therapeutic advances judged to be of utmost relevance to the treatment of OCD, based on new and emerging evidence from clinical and translational science. Areas covered include refinement in the methods of clinical assessment, the importance of early intervention based on new staging models and the need to provide sustained well-being involving effective relapse prevention. The relative benefits of psychological, pharmacological and somatic treatments are reviewed and novel treatment strategies for difficult to treat OCD, including neurostimulation, as well as new areas for research such as problematic internet use, novel digital interventions, immunological therapies, pharmacogenetics and novel forms of psychotherapy are discussed.

The Centrality of Doubting and Checking in the Network Structure of Obsessive-Compulsive Symptom Dimensions in Youth.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a heterogeneous condition with well-established symptom dimensions across the lifespan. The objective of the present study was to use network analysis to investigate the internal structure of these dimensions in unselected schoolchildren and in children with OCD. METHOD: We estimated the network structure of OCD symptom dimensions in 6,991 schoolchildren and 704 children diagnosed with OCD from 18 sites across 6 countries. All participants completed the Obsessive-Compulsive Inventory-Child Version. RESULTS: In both the school-based and clinic-based samples, the OCD dimensions formed an interconnected network with doubting/checking emerging as a highly central node, that is, having strong connections to other symptom dimensions in the network. The centrality of the doubting/checking dimension was consistent across countries, sexes, age groups, clinical status, and tic disorder comorbidity. Network differences were observed for age and sex in the school-based but not the clinic-based samples. CONCLUSION: The centrality of doubting/checking in the network structure of childhood OCD adds to classic and recent conceptualizations of the disorder in which the important role of doubt in disorder severity and maintenance is highlighted. The present results suggest that doubting/checking is a potentially important target for further research into the etiology and treatment of childhood OCD.

OCD and Anxiety: The Annual Review Issue.

Starting in 2018, the Journal began highlighting high-quality reviews in January. We called this our Annual Review Edition. This year, we have again selected a number of reviews to be placed in January, most especially from our recent call for review papers on child and adolescent anxiety and obsessive-compulsive disorder (OCD), which went out in August of 2018. We received multiple excellent submissions, and three are presented in this edition of the Journal.