Executive function (EF) difficulties in pediatric obsessive-compulsive disorder (OCD) are suggested to interact with psychotherapy response. We investigated the role of parent- and self-rated EF in a randomized trial comparing cognitive-behavioral therapy (CBT) and psychoeducation with relaxation training (PRT). We investigated the extent to which: (1) EF difficulties are evident in non-medicated pediatric OCD patients; (2) difficulties improve during psychotherapy; and (3) EF moderates symptom alleviation. We included 114 patients with OCD (aged 8–17 years), who received 14 sessions of CBT or PRT. EF was assessed before and after treatment with both the parent-rated (full age span) and self-rated (age 11–17 years) Behavior Rating Inventory of Executive Function, 2nd version (BRIEF-2). All BRIEF-2 subdomains were reported. OCD symptom severity was assessed with the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We assessed seventy-four non-psychiatric control children within a similar time interval. Parent- and self-ratings indicated EF difficulties in OCD patients compared with non-psychiatric controls across BRIEF-2 subdomains. Self-rated flexibility difficulties were associated with more severe OCD symptoms pre-treatment. Parents and children reported EF improvement after psychotherapy across subdomains. Parent-rated self-monitoring improved after CBT but not PRT. EF improvement was not associated with symptom alleviation in patients. Finally, emotional control, working memory, and task-completion ability moderated OCD-symptom improvement. EF difficulties are evident at the group level in pediatric OCD and show improvement following psychotherapy with minimal differences between CBT and PRT. Although EF improvement is not associated with symptom alleviation, several subdomains of EF pre-treatment moderate the treatment effect.

Fibromyalgia is a type of generalized chronic pain condition that causes physical tenderness, fatigue, sleep disturbance, cognitive impairment, and comorbid psychiatric symptoms. Medication and psychotherapy can offer some relief. Acceptance and Commitment Therapy (ACT) is a current treatment approach that focuses on fostering acceptance of symptoms and engagement in meaningful, value-driven activities. However, no systematic attempts at investigating unwanted events and deterioration have been made in relation to ACT for fibromyalgia. This brief report presents findings on the occurrence of characteristics of such incidents in a groupbased ACT-treatment at a specialized pain clinic. Among the 94 patients included, deterioration rates were generally low across most outcome measures. Unwanted events were monitored using the 32-item Negative Effects Questionnaire, a self-report measure covering symptoms, treatment quality, dependency, stigma, hopelessness, and failure. A total of 37.6 % reported having experienced unwanted events during the treatment period, and 43.2 % at post-treatment. Among the most frequently occurring unwanted events reported at posttreatment were "Unpleasant memories resurfaced" (12.7 %), "I experienced more unpleasant feelings" (9.9 %), and "I feel like I am under more stress" (8.3 %). However, unwanted events reported during treatment were not related to treatment outcome. The results point to the importance of monitoring unwanted events during treatment, although these experiences may not interfere with benefits participants obtain, and, presumably, may be part of the theorized change process. Further research is warranted to understand how unwanted events and deterioration might affect adherence and dropout.

Pediatric obsessive-compulsive disorder (OCD) is associated with emotion regulation (ER) difficulties. Most studies are based on self-reports, while few have examined how these difficulties are expressed across modalities, which may hold important diagnostic and therapeutic information. We applied a multi-informant and multi-method approach to examine ER difficulties in 211 children aged 8-17 years: 121 with OCD and 90 non-clinical controls. Child ER difficulties were assessed with The Difficulties in Emotion Regulation Scale (self-report and parent-report) and a Tangram frustration task with investigator-rated behavior, self-rated frustration, and heart rate variability (HRV). Children with OCD differed significantly from non-clinical controls in showing: (i) elevated child ER difficulties on self-report (partial eta squared =.068-.165) and parent-report (partial eta squared =.207-.369); (ii) more investigator-rated ER difficulties during the task (Cohen's d = -.33); (iii) increased levels of self-rated frustration before and after the task (partial eta squared =.089); notably, the magnitude of this increase did not differ between children with and without OCD. Finally, (iv) all children, regardless of group, demonstrated significant HRV changes during the frustration task, with no discernible group differences in the magnitude of these changes. Results suggest the OCD-related experience of ER difficulties may not impact autonomic functioning.

BACKGROUND:Parent-child interactive processes are important factors in pediatric OCD. Understanding biological mechanisms of parent-child interactive behaviors could help improve treatment of pediatric OCD. Oxytocin has been suggested as a biological mechanism in parent-child interactions. However, no studies in pediatric OCD exist. We used machine learning to discover latent patterns in parent-child interactive behaviors and explored associations with oxytocin in children with and without OCD. METHODS:We used parent and child salivary oxytocin levels measured with enzyme-linked immunosorbent assay (ELISA) and investigator-rated parent-child behaviors during a frustration task. Children with or without OCD and their parents - 107 mother-child and 62 father-child pairs were included. We used two machine learning techniques, principal component analysis and archetypal analysis, to generate data-driven, theory-agnostic behavioral variables, and regression to estimate their associations with oxytocin. RESULTS:Principal component and archetype analyses identified behavioral patterns describing the mother-child and father-child interactions. We found a positive association between child and mother oxytocin and the interaction patterns "overinvolved interaction" and "emotional interaction" and a negative association with "distant interaction". Additionally, mother oxytocin was positively associated with "supportive interaction" and "varied-coping interaction", and negatively associated with "conflictual interaction" and "negative-low support interaction". Father oxytocin was associated with "supportive interactions" only in the presence of child OCD. CONCLUSION:Child and mother oxytocin appear related with mother-child interactive patterns. Fathers' oxytocin was related with interaction patterns only in children with OCD. Our exploratory findings can be used to generate hypothesis for future research regarding the relationship between oxytocin and maladaptive family engagement in OCD and differences between mothers and fathers' behaviors when the child has OCD.

Few randomized clinical trials (RCTs) have compared cognitive behavioral therapy (CBT) versus active control interventions for pediatric obsessive-compulsive disorder (OCD), and the range of investigated outcomes has been limited. We investigated benefits and harms of family-based CBT with exposure and response prevention (FCBT) versus family-based psychoeducation and relaxation training (FPRT) in pediatric OCD. This single-center RCT was investigator-initiated, independently funded, including participants with OCD aged 8–17 years with a Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) entry score ≥ 16. We randomized participants 1:1 to 14 sessions of FCBT versus FPRT. Allocation was masked to assessors and statisticians. The primary outcome was CY-BOCS end-of-treatment-score (week-16) analyzed by intention-to-treat. Adverse events were reported by the Negative Effects Questionnaire (NEQ-20). One-hundred-and-thirty participants were randomized, 52.3% females; mean age 13.3 (SD = 2.9) years; mean CY-BOCS total score 25.8 (SD = 4.9); n = 64 to FCBT versus n = 66 to FPRT. Sixteen participants dropped out (four from FCBT, 12 from FPRT). The mean CY-BOCS total score at end-of-treatment was significantly lower for FCBT (15.9, SD = 8.7) versus FPRT (19.9, SD = 8.1), estimate − 3.89, 95%CI [–6.83, − 0.96), p = 0.01, effect size = 0.47, 95% CI [0.09, 0.85]. This difference was below our predefined minimal clinically important difference of four points. The average weekly NEQ frequency score showed no significant group differences. FCBT was associated with significantly larger symptom reduction than FPRT, but with a modest effect. FCBT and FPRT appeared comparably tolerable. A rigorous methodology enabled the counteraction of several biases. Limitations included missing self-reported data and inability of masking participants and treatment providers.

Introduction: Oxytocin has been implicated as a biological mechanism within obsessive-compulsive disorder (OCD). Few studies only involving adults have investigated this hypothesis and found inconsistent results. We investigated whether salivary oxytocin concentrations differed between children and adolescents with and without OCD and qualified our comparative analysis by investigating the possible covariates age, pubertal stage, and sex. Methods Participants included 113 children and adolescents (8–17 years) with OCD and 88 children and adolescents without any previous or current psychiatric disorder and their parents (254 parents included). Salivary oxytocin concentrations were measured with enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using frequentist and Bayesian approaches. Results We found no evidence of a difference in mean salivary oxytocin concentrations between children and adolescents with and without OCD. Bayesian analyses indicated anecdotal to moderate support for the null hypothesis. We found an association between oxytocin and age and pubertal stage, which by visual inspection of plots and post-hoc tests indicated a nonlinear relationship. We found no association between oxytocin and sex. Conclusion Our findings do not suggest elevated oxytocin concentrations in pediatric OCD. Nonlinear changes in oxytocin across development show the importance of accounting for hormonal and behavioral changes during puberty.

The oxytocin system has been thought to contribute to obsessive-compulsive disorder (OCD). Few studies, only involving adults, have investigated this hypothesis and have found inconsistent results regarding oxytocin system activity and OCD. We investigated whether salivary oxytocin concentrations differed between children and adolescents with and without OCD and qualified our comparative analysis by investigating the possible covariates age, pubertal stage, and sex. Participants included 113 children and adolescents (8-17 years) with OCD and 88 children and adolescents without any previous or current psychiatric disorder and their parents (254 parents included). Salivary oxytocin concentrations were measured in children and parents with enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using frequentist and Bayesian approaches. We found no evidence of a difference in mean salivary oxytocin concentrations between children and adolescents with and without OCD. Bayesian analysis indicated anecdotal to moderate support for the null hypothesis. We found an association between oxytocin and age and between oxytocin and pubertal stage, which by visual inspection of plots and post-hoc tests indicated nonlinear relationships. We found no association between oxytocin concentration and sex. Our findings do not suggest elevated oxytocin concentrations in pediatric OCD. Nonlinear changes in oxytocin across development show the importance of accounting for hormonal and behavioral changes during puberty.

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.

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

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.

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.

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.

We write with great concern in response to the recent systematic review and meta-analysis of cognitive-behavioral therapy (CBT) in pediatric obsessive-compulsive disorder (OCD) by Uhre et al.1 Although the authors' results consistently support the clinical efficacy of CBT for pediatric OCD, we expect that, much like ourselves, readers will be confused by the discordant and inappropriate conclusions that they put forward. These conclusions stem from the authors' application and interpretation of their particular qualitative methods, which could lead important stakeholders (eg, parents, patients, clinicians, and payers) to wrongly discount clear evidence for what is known to be the best evidence-based therapy for pediatric OCD.

Chlorpyrifos (CPF) is a toxic organophosphate commonly used worldwide. Its residues are being detected in different environmental matrixes and hence in the food chain. Repeated CPF exposure might pose health risk for the general population on long term. This data article contains the data of contractility impairment further to dietary exposure to CPF on a hind limb skeletal muscle; soleus, a typical slow twitch skeletal muscle. Thirty adult male rats Sprague Dawley are divided into three groups receiving the following daily diet for 6 weeks: Group 1 (vehicle), Group 2: CPF1 (CPF 1mg/kg/day) and Group 3: CPF5 (CPF 5 mg/kg/day). Soleus twitch tension and fatigability index are determined at the end of the treatment. The activity of acteylcholinesterase enzyme is assessed in the tissues homogenate. Additionally, we examined the expression levels of ryanodine type 1 receptor (RyR1), ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 1 (Atp2a1), ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2 (Atp2a2) and nicotinic acetylcholine receptor (nAChR) in CPF-exposed skeletal muscle tissue using quantitative real time polymerase chain reaction.CPF exposure at two different doses induced an increase in twitch contraction in soleus muscle along with an increase in fatigability index. These increases are accompanied by low level of acetylcholinesterase enzyme activity as well as modification in genes level expression of nAChR, RyR1, Atp2a1 and Atp2a2 involved in contractility.