Exposure Quality in Cognitive Behavioral Treatment for Youth Anxiety Disorders—Predictors and Associations with Outcomes

To optimize cognitive behavioral therapy (CBT) outcomes for anxiety disorders in youth, more knowledge is needed about how specific CBT components work. Exposure to feared situations is an effective CBT component. However, there is little observation-based empirical research on how exposure relates to outcomes and other clinical variables. In a randomized controlled community clinic trial for youth with anxiety disorders, observers reliably rated exposure quality for 68 youths aged 8 to 15 years based on 118 videotaped sessions. The treatment program was the manual-based FRIENDS program. Three exposure quality elements (preparation, post-processing, and parent contribution to exposure) were examined in relation to pre-treatment demographic and clinical variables, outcomes, and youth- and therapist-rated alliance using multilevel hierarchical regression models. The outcomes were diagnostic recovery, clinical severity and anxiety symptoms change from pre- to post-treatment and one-year follow-up, and treatment dropout. The results showed that parent contribution to exposure was higher for boys and younger children. Parent contribution to exposure, but no other exposure element, was associated with a larger likelihood of diagnostic recovery and larger clinical severity reduction at one-year follow-up. Exposure quality was unrelated to outcomes at post-treatment, dropout, or alliance. We conclude that enhancing parent contribution to exposure during treatment could improve long-term outcomes after CBT for youth anxiety disorders. Exposure elements should be observed in larger samples to further examine their potential role for CBT outcomes.publishedVersio

Development and feasibility testing of a physical activity intervention for youth with anxiety and depression : a study protocol

Background: Anxiety and depressive disorders in children and adolescents are highly prevalent and account for more than half of all youth psychiatric disorders. Left untreated, anxiety, and depression lead to numerous detrimental outcomes, including reduced quality of life, psychiatric, and somatic comorbidity and even reduced lifespan. This puts a large strain on child and adolescent mental healthcare services (CAMHS) to provide effective treatments. However, even when provided the best evidence-based treatment, between 40–50% of patients continue to report significant symptom burdens. Thus, there is an immediate need for supplemental and/or new treatment approaches. Physical activity as a supplementary treatment may be such an approach. However, research investigating this approach within this population is scant. This protocol paper describes the development and feasibility trial of a physical activity-based intervention targeting anxiety and depressive symptoms in youth treated in CAMHS. Methods/design: The study is based on the UK Medical Council Research Framework (MRC) for developing and evaluating complex interventions. Feasibility and acceptability of the physical activity intervention (confident, active, and happy youth) will be evaluated in an uncontrolled open-label trial using qualitative and quantitative data. Twenty youths with anxiety and/or depressive symptoms will be recruited. Acceptability of assessment procedures, the intervention, and perceived benefits and barriers to participation will be assessed, and qualitative interviews with participants, caregivers, and referring specialists will explore contextual and practical factors associated with intervention delivery. Physical activity will be measured using the Actigraph GT3X+ monitor at baseline, and post-intervention and change in anxiety and depression will be assessed. Discussion: This study will contribute to the development of supplementary physical treatment interventions for youth with anxiety and depression in contact with CAMHS. The goal is to examine new avenues of treatment that ultimately may improve upon current treatment outcomes of anxiety and depression. This work will be in preparation for a future definitive randomized controlled trial (RCT) of this approach, in line with the MRC Framework. Trial registration: ClnicalTrials.gov, NCT05049759. Registered on August 19, 2021. Retrospectively registered

Feasibility of a physical activity intervention for children and adolescents with anxiety and depression

Background Physical activity is identified as a key modifiable factor towards good short- and long-term mental health and has shown positive effects on anxiety and depression in children and adolescents. However, physical activity-based interventions are not a part of standard mental health care and evidence on the effect of such interventions is still lacking. A transdiagnostic, physical activity-based intervention was developed as a supplement to routine clinical care for youth in specialized child and adolescent mental health services. Methods /design. The feasibility of the physical activity intervention (Confident, Active, and Happy Youth) was evaluated in an open-label study by assessing the recruitment process, acceptability, intervention suitability, contentment, and preliminary intervention effects in the form of youth and parent-rated anxiety and depressive symptoms. Physical activity levels were objectively measured using Actigraph™ physical activity sensors, and progression to a definitive study was evaluated in accordance with a priori criteria. Results In total 21 of 25 eligible youth consented to participate, two dropped out of the intervention and 19 completed (76% of eligible participants). The retention rate among consenting participants was 89% and mean attendance to sessions was 83%. The suitability of the intervention was rated as good by the youth and their parents, and intervention contentment was rated high. Changes in youth and parent-rated symptom measures following the intervention were negligible, except for parent-rated anxiety symptoms assessed at 10-month follow-up. Accelerometer data indicated lower levels of moderate to vigorous activity during sessions than intended. No adverse effects were noted. Conclusion This feasibility study met the pre-determined progression criteria to a definitive study. Thus, a larger trial with longer follow-up should be conducted to explore the effect of the intervention. Trial registration ClnicalTrials.gov, NCT05049759. Retrospectively registered, 20.09.2021

Genetic variation in the endocannabinoid system and response to cognitive behavioural therapy for child anxiety disorders

Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re-emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre- and post-treatment and during the follow-up period in the full sample and a subset with fear-based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P < 0.05) with two SNPs. During the follow-up period, five SNPs were nominally associated with a poorer treatment response (rs806365 [CNR1]; rs2501431 [CNR2]; rs2070956 [CNR2]; rs7769940 [CNR1]; rs2209172 [FAAH]) and one with a more favorable response (rs6928813 [CNR1]). Within the fear-based subset, the effect of rs806365 survived multiple testing corrections (P < 0.0016). We found very limited evidence for an association between variants in endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility

The impact of treatment delivery format on response to Cognitive Behaviour Therapy for pre-adolescent children with anxiety disorders

Background. Several delivery formats of Cognitive Behaviour Therapy (CBT) for child anxiety have been proposed, however there is little consensus on the optimal delivery format. The primary goal of this study was to investigate the impact of the child’s primary anxiety diagnosis on changes in clinical severity (of the primary problem) during individual CBT, group CBT, and guided parent-led CBT. The secondary goal was to investigate the impact of the child’s primary anxiety diagnosis on rates of remission for the three treatment formats. Methods. A sample of 1253 children (5 – 12 years; Mage = 9.3, SD = 1.7) was pooled from CBT trials carried out at 10 sites. Children had a primary diagnosis of Generalised Anxiety Disorder (GAD), Social Anxiety Disorder (SoAD), Specific Phobia (SP) or Separation Anxiety Disorder (SAD). Children and parents completed a semi-structured clinical interview to assess the presence and severity of DSM-IV psychiatric disorders at pre intervention, post intervention and follow-up. Linear mixture modelling was used to evaluate the primary research question and logistic modelling was used to investigate the secondary research question. Results. Children with a primary diagnosis of GAD, SoAD and SAD demonstrated comparable improvements in clinical severity to all three CBT treatment formats. However, children with primary SP showed significantly larger reductions in clinical severity following individual CBT compared to group CBT and guided parent-led CBT. The results were mirrored in the analysis of remission responses with the exception that individual CBT was no longer superior to group CBT for children with a primary SP. Furthermore, the difference between individual and group was not significant when the follow-up data was examined separately. Conclusions. The data show that there may be greater clinical benefit by allocating children with a primary SP to individual CBT, although future research on cost-effectiveness is needed to determine whether the additional clinical benefits justify the additional resources required

Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts

Research Review: Recommendations for reporting on treatment trials for child and adolescent anxiety disorders - an international consensus statement

Background: Anxiety disorders in children and young people are common and bring significant personal and societal costs. Over the last two decades, there has been a substantial increase in research evaluating psychological and pharmacological treatments for anxiety disorders in children and young people and exciting and novel research has continued as the field strives to improve efficacy and effectiveness, and accessibility of interventions. This increase in research brings potential to draw together data across studies to compare treatment approaches and advance understanding of what works, how, and for whom. There are challenges to these efforts due largely to variation in studies' outcome measures and variation in the way study characteristics are reported, making it difficult to compare and/or combine studies, and this is likely to lead to faulty conclusions. Studies particularly vary in their reliance on child, parent, and/or assessor-based ratings across a range of outcomes, including remission of anxiety diagnosis, symptom reduction, and other domains of functioning (e.g., family relationships, peer relationships). Methods: To address these challenges, we convened a series of international activities that brought together the views of key stakeholders (i.e., researchers, mental health professionals, young people, parents/caregivers) to develop recommendations for outcome measurement to be used in treatment trials for anxiety disorders in children and young people. Results and conclusions: This article reports the results of these activities and offers recommendations for selection and reporting of outcome measures to (a) guide future research and (b) improve communication of what has been measured and reported. We offer these recommendations to promote international consistency in trial reporting and to enable the field to take full advantage of the great opportunities that come from data sharing going forward

Exposure Quality in Cognitive Behavioral Treatment for Youth Anxiety Disorders—Predictors and Associations with Outcomes

To optimize cognitive behavioral therapy (CBT) outcomes for anxiety disorders in youth, more knowledge is needed about how specific CBT components work. Exposure to feared situations is an effective CBT component. However, there is little observation-based empirical research on how exposure relates to outcomes and other clinical variables. In a randomized controlled community clinic trial for youth with anxiety disorders, observers reliably rated exposure quality for 68 youths aged 8 to 15 years based on 118 videotaped sessions. The treatment program was the manual-based FRIENDS program. Three exposure quality elements (preparation, post-processing, and parent contribution to exposure) were examined in relation to pre-treatment demographic and clinical variables, outcomes, and youth- and therapist-rated alliance using multilevel hierarchical regression models. The outcomes were diagnostic recovery, clinical severity and anxiety symptoms change from pre- to post-treatment and one-year follow-up, and treatment dropout. The results showed that parent contribution to exposure was higher for boys and younger children. Parent contribution to exposure, but no other exposure element, was associated with a larger likelihood of diagnostic recovery and larger clinical severity reduction at one-year follow-up. Exposure quality was unrelated to outcomes at post-treatment, dropout, or alliance. We conclude that enhancing parent contribution to exposure during treatment could improve long-term outcomes after CBT for youth anxiety disorders. Exposure elements should be observed in larger samples to further examine their potential role for CBT outcomes

Socio-emotional problems in boys with sex chromosome aneuploidies compared to a clinical sample

Boys with sex chromosome aneuploidies (SCA) represent an understudied group. We examined parent-reported physical and socio-emotional problems in 25 boys with SCA (Mean age = 11.7 years, SD = 4.5). The majority had no severe physical health problems. One third of the sample had sleep problems and half of them had weekly or monthly pain. Total emotional and behavior problems, as assessed with the Strengths and Difficulties Questionnaire, were at the same level as reported for boys referred to child mental health clinics. Thus, boys with SCA may have the same need for psychological assessment and intervention as clinic-referred boys