Atypical neurocognitive functioning in children and adolescents with obsessive-compulsive disorder (OCD).

Atypical neurocognitive functioning has been found in adult patients with obsessive-compulsive disorder (OCD). However, little work has been done in children and adolescents with OCD. In this study, we investigated neurocognitive functioning in a large and representative sample of newly diagnosed children and adolescents with OCD compared to non-psychiatric controls. Children and adolescents with OCD (n = 119) and non-psychiatric controls (n = 90) underwent psychopathological assessment, intelligence testing, and a neurocognitive test battery spanning cognitive flexibility, planning and decision-making, working memory, fluency, and processing speed. The MANOVA main effect revealed that children and adolescents with OCD performed significantly worse than the control group (p < .001, [Formula: see text] = 0.256). Atypical patient performance was particularly found for indices of cognitive flexibility, decision-making, working memory, and processing speed. We found no evidence of differences in planning or fluency. Moreover, we found no significant associations between neurocognitive performance and OCD symptom severity or comorbidity status. Our results indicate that children and adolescents with OCD show selective atypical neurocognitive functioning. These difficulties do not appear to drive their OCD symptoms. However, they may contribute to lifespan difficulties and interfere with treatment efficacy, an objective of our research currently.

Adverse events in cognitive behavioral therapy and relaxation training for children and adolescents with obsessive-compulsive disorder: A mixed methods study and analysis plan for the TECTO trial.

Background: Knowledge on adverse events in psychotherapy for youth with OCD is sparse. No official guidelines exist for defining or monitoring adverse events in psychotherapy. Recent recommendations call for more qualitative and quantitative assessment of adverse events in psychotherapy trials. This mixed methods study aims to expand knowledge on adverse events in psychotherapy for youth with OCD. Methods: This is an analysis plan for a convergent mixed methods study within a randomized clinical trial (the TECTO trial). We include at least 128 youth aged 8-17 years with obsessive-compulsive disorder (OCD). Participants are randomized to either family-based cognitive behavioral therapy (FCBT) or family-based psychoeducation and relaxation training (FPRT). Adverse events are monitored quantitatively with the Negative Effects Questionnaire. Furthermore, we assess psychiatric symptoms, global functioning, quality of life, and family factors to investigate predictors for adverse events. We conduct semi-structured qualitative interviews with all youths and their parents on their experience of adverse events in FCBT or FPRT. For the mixed methods analysis, we will merge 1) a qualitative content analysis with descriptive statistics comparing the types, frequencies, and severity of adverse events; 2) a qualitative content analysis of the perceived causes for adverse events with prediction models for adverse events; and 3) a thematic analysis of the participants' treatment evaluation with a correlational analysis of adverse events and OCD severity. Discussion: The in-depth mixed methods analysis can inform 1) safer and more effective psychotherapy for OCD; 2) instruments and guidelines for monitoring adverse events; and 3) patient information on potential adverse events. The main limitation is risk of missing data. Trial registration: ClinicalTrials.gov identifier: NCT03595098. Registered on July 23, 2018.

Inhibitory control in obsessive compulsive disorder: A systematic review and activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies.

BACKGROUND: Patients with obsessive compulsive disorder (OCD) often show deficits in inhibitory control, which may underlie poor control over obsessions and compulsions. Several functional magnetic resonance imaging (fMRI) experiments utilizing a variety of tasks have investigated the neural correlates of inhibitory control in OCD. Evidence from existing meta-analyses suggests aberrant activation of regions in fronto-striatal circuits during inhibitory control. However, new fMRI articles have since been published, and a more rigorous methodology for neuroimaging meta-analyses is now available. OBJECTIVES: First, to reevaluate the evidence for abnormal brain activation during performance of inhibitory control tasks in OCD while adhering to current best practices for meta-analyses, and second, to extend previous findings by separately assessing different subprocesses of inhibitory control. METHOD: We systematically searched Web of Knowledge, ScienceDirect, Scopus, PubMed and the functional BrainMap database for fMRI articles that compared activation during performance of inhibitory control tasks in patients with OCD and healthy control (HC) subjects. Thirty-five experiments from 21 articles met our criteria for inclusion. We first performed activation-likelihood-estimation meta-analyses to elucidate brain areas in which case-control activation differences converged across articles and tasks. We then aimed to extend previous work by separately evaluating experiments requiring inhibition of a prepotent response without execution of an alternative response (i.e., response inhibition) and experiments requiring inhibition of a prepotent response and execution of an alternative response (i.e., cognitive inhibition). RESULTS: The 35 experiments included a total of 394 patients and 410 controls. We did not find evidence of abnormal brain activation in OCD during inhibitory control when pooling data from all experiments. Analysis restricted to cognitive inhibition experiments showed abnormal activation of the dorsal anterior cingulate cortex (dACC; P = .04, cluster-level familywise error-corrected, cluster volume of 824 mm3). We did not have sufficient data to evaluate response inhibition experiments separately. CONCLUSION: Findings of abnormal brain activation in OCD from different inhibitory control tasks do not appear to converge on the same brain regions, but the dACC may be implicated in abnormal cognitive inhibition. Our findings highlight a need for experiments that specifically target subprocesses of inhibitory control to achieve a more differentiated understanding of the neural correlates for impaired inhibitory control in OCD.

Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents (the TECTO trial): a statistical analysis plan for the randomised clinical trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder which affects up to 3% of children and adolescents. OCD in children and adolescents is generally treated with cognitive behavioural therapy (CBT), which, in more severely affected patients, can be combined with antidepressant medication. The TECTO trial aims to compare the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation/relaxation training (FPRT) in children and adolescents aged 8 to 17 years. This statistical analysis plan outlines the planned statistical analyses for the TECTO trial. METHODS: The TECTO trial is an investigator-initiated, independently funded, single-centre, parallel-group, superiority randomised clinical trial. Both groups undergo 14 sessions of 75 min each during a period of 16 weeks with either FCBT or FPRT depending on the allocation. Participants are randomised stratified by age and baseline Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score. The primary outcome is the CY-BOCS score. Secondary outcomes are health-related quality of life assessed using KIDSCREEN-10 and adverse events assessed by the Negative Effects Questionnaire (NEQ). Primary and secondary outcomes are assessed at the end of the intervention. Continuous outcomes will be analysed using linear regression adjusted for the stratification variables and baseline value of the continuous outcome. Dichotomous outcomes will be analysed using logistic regression adjusted for the stratification variables. The statistical analyses will be carried out by two independent blinded statisticians. DISCUSSION: This statistical analysis plan includes a detailed predefined description of how data will be analysed and presented in the main publication before unblinding of study data. Statistical analysis plans limit selective reporting bias. This statistical analysis plan will increase the validity of the final trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT03595098. July 23, 2018.

Associations Between the Severity of Obsessive-Compulsive Disorder and Vocal Features in Children and Adolescents: Protocol for a Statistical and Machine Learning Analysis.

BACKGROUND: Artificial intelligence tools have the potential to objectively identify youth in need of mental health care. Speech signals have shown promise as a source for predicting various psychiatric conditions and transdiagnostic symptoms. OBJECTIVE: We designed a study testing the association between obsessive-compulsive disorder (OCD) diagnosis and symptom severity on vocal features in children and adolescents. Here, we present an analysis plan and statistical report for the study to document our a priori hypotheses and increase the robustness of the findings of our planned study. METHODS: Audio recordings of clinical interviews of 47 children and adolescents with OCD and 17 children and adolescents without a psychiatric diagnosis will be analyzed. Youths were between 8 and 17 years old. We will test the effect of OCD diagnosis on computationally derived scores of vocal activation using ANOVA. To test the effect of OCD severity classifications on the same computationally derived vocal scores, we will perform a logistic regression. Finally, we will attempt to create an improved indicator of OCD severity by refining the model with more relevant labels. Models will be adjusted for age and gender. Model validation strategies are outlined. RESULTS: Simulated results are presented. The actual results using real data will be presented in future publications. CONCLUSIONS: A major strength of this study is that we will include age and gender in our models to increase classification accuracy. A major challenge is the suboptimal quality of the audio recordings, which are representative of in-the-wild data and a large body of recordings collected during other clinical trials. This preregistered analysis plan and statistical report will increase the validity of the interpretations of the upcoming results. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39613.

Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial).

BACKGROUND: Cognitive behavioural therapy (CBT) is the recommended first-line treatment for children and adolescents with obsessive-compulsive disorder (OCD), but evidence concerning treatment-specific benefits and harms compared with other interventions is limited. Furthermore, high risk-of-bias in most trials prevent firm conclusions regarding the efficacy of CBT. We investigate the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation and relaxation training (FPRT) in youth with OCD in a trial designed to reduce risk-of-bias. METHODS: This is an investigator-initiated, independently funded, single-centre, parallel group superiority randomised clinical trial (RCT). Outcome assessors, data managers, statisticians, and conclusion drawers are blinded. From child and adolescent mental health services we include patients aged 8-17 years with a primary OCD diagnosis and an entry score of ≥16 on the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We exclude patients with comorbid illness contraindicating trial participation; intelligence quotient < 70; or treatment with CBT, PRT, antidepressant or antipsychotic medication within the last 6 months prior to trial entry. Participants are randomised 1:1 to the experimental intervention (FCBT) versus the control intervention (FPRT) each consisting of 14 75-min sessions. All therapists deliver both interventions. Follow-up assessments occur in week 4, 8 and 16 (end-of-treatment). The primary outcome is OCD symptom severity assessed with CY-BOCS at end-of-trial. Secondary outcomes are quality-of-life and adverse events. Based on sample size estimation, a minimum of 128 participants (64 in each intervention group) are included. DISCUSSION: In our trial design we aim to reduce risk-of-bias, enhance generalisability, and broaden the outcome measures by: 1) conducting an investigator-initiated, independently funded RCT; 2) blinding investigators; 3) investigating a representative sample of OCD patients; 3) using an active control intervention (FPRT) to tease apart general and specific therapy effects; 4) using equal dosing of interventions and therapist supervision in both intervention groups; 5) having therapists perform both interventions decided by randomisation; 6) rating fidelity of both interventions; 7) assessing a broad range of benefits and harms with repeated measures. The primary study limitations are the risk of missing data and the inability to blind participants and therapists to the intervention. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03595098, registered July 23, 2018.

Dr. Uhre et al. Reply.

In a recent letter to the editor, a group of clinician-researchers posit that the conclusions in our published systematic review1 on cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD) are based on inappropriate methodology. In this reply, we address the concerns expressed by Storch et al.2.

Systematic Review and Meta-Analysis: Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder in Children and Adolescents.

OBJECTIVE: To assess benefits and harms of cognitive-behavioral therapy (CBT) versus no intervention or versus other interventions for pediatric obsessive-compulsive disorder (OCD). METHOD: We searched for randomized clinical trials of CBT for pediatric OCD. Primary outcomes were OCD severity, serious adverse events, and level of functioning. Secondary outcomes were quality of life and adverse events. Remission from OCD was included as an exploratory outcome. We assessed risk of bias and evaluated the certainty of the evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Nine trials (N = 645) were included comparing CBT with no intervention and 3 trials (N = 146) comparing CBT with selective serotonin reuptake inhibitors (SSRIs). Compared with no intervention, CBT decreased OCD severity (mean difference [MD] = -8.51, 95% CI = -10.84 to -6.18, p < .00001, low certainty), improved level of functioning (patient-rated: standardized MD [SMD] = -0.90, 95% CI = -1.19 to -0.62, p < .00001, very low certainty; parent-rated: SMD = -0.68, 95% CI = -1.12 to -0.23, p = .003, very low certainty), had similar proportions of participants with adverse events (risk ratio = 1.06, 95% CI = 0.93-1.22, p = .39, GRADE: low certainty), and was associated with reduced risk of still having OCD (risk ratio = 0.50, 95% CI = 0.37-0.67, p < .00001, very low certainty). We had insufficient data to assess the effect of CBT versus no intervention on serious adverse events and quality of life. Compared with SSRIs, CBT led to similar decreases in OCD severity (MD = -0.75, 95% CI = -3.79 to 2.29, p = .63, GRADE: very low certainty), and was associated with similar risk of still having OCD (risk ratio = 0.85, 95% CI = 0.66-1.09, p = .20, very low certainty). We had insufficient data to assess the effect of CBT versus SSRIs on serious adverse events, level of functioning, quality of life, and adverse events. CONCLUSION: CBT may be more effective than no intervention and comparable to SSRIs for pediatric OCD, but we are very uncertain about the effect estimates.

A free and simple computerized screening test for visual field defects.

About 30-40% of stroke patients suffer from visual field defects following injury. These can interfere with the standard neuropsychological assessment and complicate the interpretation of tests that use visual materials. However, information about the integrity of a patient's central visual field is often unavailable. We, therefore, designed a screening tool, the computerized visual field test (c-VFT), specifically targeted at providing easily available, but rough, information about patients' central visual field. c-VFT was tested in two samples of stroke patients. Eleven patients were tested on c-VFT and on the Esterman test. Five patients were tested on c-VFT and the Humphrey Visual Field Analyzer (HFA), central 10-2. Criterion validity of the c-VFT was investigated by calculating quadrantwise intraclass correlation for both comparisons. For the HFA comparison, we also calculated point-to-point intraclass correlation, sensitivity, and specificity. Analyses revealed moderately good correspondence between c-VFT and the Esterman test, and between c-VFT and HFA 10-2, respectively. When looking specifically at test points within one degree of visual angle apart in the two tests, intraclass correlation increased. For these points, the sensitivity of c-VFT was 0.89 and specificity was 0.97. While the c-VFT is not designed to be diagnostic nor to replace the detailed visual field analysis, this study shows that it provides a reasonable screening of the central visual field. The test can easily be used and will be made freely available to neuropsychological clinicians and researchers.

Effects of different delayed exercise regimens on cognitive performance in fimbria­fornix transected rats.

Studies have shown that exercise can positively influence cognitive performance after brain injury. This study investigated the effects of different exercise regimens on allocentric place learning after fimbria­fornix (FF) transection. One hundred and sixteen pre­shaped rats were subjected either to a mechanical transection of the FF or control sham surgery and divided into following groups: i) no exercise (NE), ii) voluntary exercise in a running wheel (RW), iii) forced swimming exercise administered as interval training of short (3x5 min) duration (FS­SI), iv) forced swimming exercise administered as interval training of long (3x15 min) duration (FS­LI), v) forced swimming exercise administered as one session of short (5 min) duration (FS­SS), and vi) forced swimming exercise administered as one session of long (15 min) duration (FS­LS). The exercise was initiated 21 days post­surgery. Subsequently, all animals were administered 28 acquisition sessions in an 8­arm radial maze. Both sham operated and lesioned animals showed a significant learning response, however, the lesion induced a marked and lasting impairment, which was not alleviated neither by voluntary nor forced (spaced or one­session only) exercise regimens. Exercise regimens had no effect on the place learning of control sham animals. We conclude that the lesion location as well as factors related to the exercise­ and cognitive testing protocols can profoundly influence the potential of exercise as a general recovery­promoting method.