Patterns of sub-optimal change following CBT for childhood anxiety.

BACKGROUND: Children and adolescents demonstrate diverse patterns of symptom change and disorder remission following cognitive behavioural therapy (CBT) for anxiety disorders. To better understand children who respond sub-optimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diagnosis immediately following treatment or at any point during the 12 months following treatment. METHODS: Data were collected from 10 clinical sites with assessments at pre-and post-treatment and at least once more at 3, 6 or 12-month follow-up. Participants were assigned to one of three groups based on diagnostic status for youths who: (a) retained an anxiety diagnosis from post to end point (minimal responders); (b) remitted anxiety diagnoses at post but relapsed by end point (relapsed responders); and (c) retained a diagnosis at post but remitted to be diagnosis free at end point (delayed responders). Growth curve models assessed patterns of change over time for the three groups and examined predictors associated with these patterns including demographic, clinical and parental factors, as well as treatment factors. RESULTS: Higher primary disorder severity, being older, having a greater number of anxiety disorders, having social anxiety disorder, as well as higher maternal psychopathology differentiated the minimal responders from the delayed and relapsed responders at the baseline. Results from the growth curve models showed that severity of the primary disorder and treatment modality differentiated patterns of linear change only. Higher severity was associated with significantly less improvement over time for the minimal and relapsed response groups, as was receiving group CBT, when compared to the delayed response group. CONCLUSIONS: Sub-optimal response patterns can be partially differentiated using variables assessed at pre-treatment. Increased understanding of different patterns of change following treatment may provide direction for clinical decision-making and for tailoring treatments to specific groups of clinically anxious youth. Future research may benefit from assessing progress during treatment to detect emerging response patterns earlier.

Cognitive behavior therapy for adult eating disorders in routine clinical care: A systematic review and meta-analysis.

OBJECTIVE: Cognitive behavior therapy (CBT) is a recommended treatment for eating disorders (ED) in adults given its evidence, mainly based on efficacy studies. However, little is known about how CBT works in routine clinical care. The goal of the present meta-analysis is to investigate how CBT works for various ED when carried out in routine clinical settings. METHOD: Ovid MEDLINE, Embase OVID, and PsycINFO were systematically searched for articles published until June 2023. The outcome of CBT, methodological quality, risk of bias (RoB), and moderators of treatment outcome were examined and benchmarked by meta-analytically comparing with efficacy studies for ED. Fifty studies comprising 4299 participants who received CBT were included. RESULTS: Large within-group effect sizes (ES) were obtained for ED-psychopathology at post-treatment (1.12), and follow-up (1.22), on average 9.9 months post-treatment. Attrition rate was 25.5% and RoB was considerable in the majority of studies. The benchmarking analysis showed that effectiveness studies had very similar ESs as efficacy studies (1.20 at post-treatment and 1.28 at follow-up). CONCLUSION: CBT for ED is an effective treatment when delivered in routine clinical care, with ESs comparable to those found in efficacy studies. However, the evidence needs to be interpreted with caution due to the RoB in a high proportion of studies. PUBLIC SIGNIFICANCE: Eating disorders are common in the population and often lead to multiple negative consequences. CBT has been found effective for ED and is recommended in clinical guidelines. Since these recommendations are primarily based on university studies we wanted to investigate how CBT performs in routine clinical care. Our meta-analysis found that CBT worked as well in routine care as in university setting studies.

OBJETIVO: La terapia cognitivo-conductual (TCC) es un tratamiento recomendado para los trastornos de la conducta alimentaria (TCA) en adultos debido a su evidencia, basada principalmente en estudios de eficacia. Sin embargo, se sabe poco sobre cómo funciona la TCC en la atención clínica rutinaria. El objetivo de este meta-análisis es investigar cómo funciona la TCC para diversos TCA cuando se lleva a cabo en entornos clínicos habituales. MÉTODO: Se realizó una búsqueda sistemática en Ovid MEDLINE, Embase OVID y PsycINFO de artículos publicados hasta junio de 2023. Se examinaron el resultado de la TCC, la calidad metodológica, el riesgo de sesgo y los moderadores del resultado del tratamiento, y se compararon metaanalíticamente con estudios de eficacia para TCA. Se incluyeron cincuenta estudios que comprendían a 4299 participantes que recibieron TCC. RESULTADOS: Se obtuvieron tamaños del efecto (TE) grandes dentro del grupo para la patología de los TCA en el post-tratamiento (1.12) y en el seguimiento (1.22), en promedio 9.9 meses después del post-tratamiento. La tasa de abandono fue del 25.5% y el riesgo de sesgo fue considerable en la mayoría de los estudios. El análisis de comparación mostró que los estudios de efectividad tenían TE muy similares a los estudios de eficacia (1.20 en el post-tratamiento y 1.28 en el seguimiento). CONCLUSIÓN: La TCC para los TCA es un tratamiento efectivo cuando se administra en la atención clínica rutinaria, con TE comparables a los encontrados en estudios de eficacia. Sin embargo, la evidencia debe interpretarse con cautela debido al riesgo de sesgo en una alta proporción de los estudios.

Evaluation of dialectical behavior therapy for adolescents in routine clinical practice: a pre-post study.

BACKGROUND: Self-harm and suicidal ideation are prevalent among adolescents, cause physical and psychosocial disability, and have potentially life-threatening consequences. Dialectical behavioral therapy for Adolescents (DBT-A) is an evidence-based intervention for reducing self-harm. However, few studies have investigated the effectiveness of DBT-A when delivered in routine clinical practice. METHODS: A follow-up cohort study, based on data from a quality assessment register of DBT-A in child and adolescent mental health services including seven outpatient clinics. Inclusion criteria were ongoing or a history of self-harming behavior the last 6 months; current suicidal behavior; at least 3 criteria of DSM-IV Borderline personality disorder (BPD), or at least the self-destruction criterion of DSM-IV BPD, in addition to minimum 2 subthreshold criteria; and fluency in Norwegian. Participants received 20 weeks of DBT-A consisting of multifamily skills training groups and individual therapy sessions. Outcomes from 41 participants included frequency of self-harm, suicide attempts and hospitalizations caused by self-harm or suicide attempts, assessed pre-, during, and post-treatment by self-report and reviews of the patient's medical records. Suicidal ideation, urge to self-harm and perceived feelings of happiness and sadness were assessed by the patients' diary cards at week 1, 5, 10, 15 and 20 of the treatment program. RESULTS: Participants attended an average of 17.9 (SD = 4.7) individual sessions, 14.7 (SD = 3.4) group-based skills training sessions and 4.6 (SD = 4.1) brief intersession telephone consultations. Moderate to large within-group effect sizes (ES) were found in self-harm from pre-treatment to 1-5 weeks (d = 0.64), 6-10 weeks (d = 0.84), 11-15 weeks (d = 0.99), 16-20 weeks (d = 1.26) and post-treatment (d = 1.68). Nine participants were admitted to hospitalization during DBT-A, whereas five had attempted suicide, but no suicides were completed. No statistically significant changes were found in suicidal ideation, urge to self-harm or perceived feelings of happiness or sadness from pre to post treatment. CONCLUSION: The findings of the current study are promising as the participants reported considerably reduced self-harm behavior after DBT-A treatment in a child and adolescent mental health outpatient setting.

Family therapy and cognitive behavior therapy for eating disorders in children and adolescents in routine clinical care: a systematic review and meta-analysis.

Family therapy for eating disorders (ED) is well-established and represents the treatment choice for ED in children and adolescents according to guidelines, with cognitive behavior therapy (CBT) as a second line treatment. There is limited knowledge about how these treatments work in routine clinical care. The goal of the present meta-analysis is to investigate the effectiveness of family therapy and CBT for various EDs in children and adolescents when carried out in routine clinical care. Ovid MEDLINE, Embase OVID, and PsycINFO were searched for articles published until December 2023. The outcome of family therapy and CBT, methodological quality, risk of bias, and moderators of treatment outcome were examined and benchmarked by meta-analytically comparing with ED efficacy studies. Forty-four effectiveness studies comprising 3251 family therapy or CBT patients were included. Large to very large within-group effect sizes (ES) were found for ED-psychopathology (0.80) and weight measures for AN (1.64) at post treatment. The attrition rate was 15%. Risk of bias was considerable. Moderate to large ES were found for family therapy and CBT, respectively. The benchmarking analysis showed that effectiveness studies had comparable ESs to efficacy studies (0.80 and 0.84 for the ED-psychopathology at post treatment). The findings support family therapy and CBT for ED in children and adolescents as effective treatments when delivered in routine clinical care, with effects comparable with those found in efficacy studies. The evidence needs to be interpreted with caution because of the risk of bias in a high proportion of studies.PROSPERO [CRD42023441794].

Group cohesion and alliance predict cognitive-behavioral group treatment outcomes for youth with anxiety disorders.

Knowledge about how to enhance group cognitive behavioral therapy (GCBT) outcomes is needed. In a randomized controlled effectiveness trial, we examined group cohesion (the bond between group members) and the alliance (the client-clinician bond) as predictors of GCBT outcomes. The sample was 88 youth (M age 11.7 years, SD = 2.1; 54.5% girls; 90.7% White) with anxiety disorders. Observers rated group cohesion and alliance in 32 sessions from 16 groups. We examined early group cohesion and alliance (r = .50, p < .001) and group cohesion and alliance change from early to late in treatment in relation to outcomes using generalized estimation equations accounting for nesting within groups (ICCs .31 to .55). The outcomes were diagnostic recovery, clinical severity, and parent- and youth-reported anxiety symptoms, each at post-treatment, 12-months, and 4-years follow-up. There were more significant associations with 4-years follow-up than earlier outcomes. Clinical severity and parent-reported anxiety symptoms were more frequently predicted than diagnostic recovery. Clinician- and parent-reported outcomes were far more frequently significantly predicted by cohesion and alliance than youth-rated outcomes. We conclude that group cohesion and alliance are related but distinct variables, both associated with some GCBT outcomes for as long as 4 years after treatment.

Parental Early Life Maltreatment and Related Experiences in Treatment of Youth Anxiety Disorder.

The role of parents' early life maltreatment (ELM) (e.g. physical, sexual abuse) and related experiences, in relation to offspring anxiety is not well understood. The current study investigated the association between self-reported depression and ELM and related experiences in mothers (n = 79) and fathers (n = 50), and mother-, father-, and youth-reported symptoms of youth anxiety (n = 90). Outcomes were assessed at pre,- and posttreatment and 3-, 6-, and 12-months follow-up. Parental ELM were not associated with pre-treatment differences or differences in outcome of treatment. However ELM related experiences were associated with increased mother-, father-, and youth-rated youth anxiety at pretreatment. Fathers depressive symptoms were found to mediate the relationship between father ELM related experiences and father-rated youth anxiety symptoms. Future research is warranted on parental ELM and depression as factors affecting outcomes of treatment of youth anxiety. Trial registered at: helseforskning.etikkom.no (reg. nr. 2017/1367).

The Therapy Process Observational Coding System: Group cohesion scale in youth anxiety treatment: Psychometric properties.

BACKGROUND: There are no well-established measures of group cohesion, defined as the collaborative bond between group members, in group cognitive behavioral therapy (GCBT) with youth. We therefore examined the Therapy Process Observational Coding System for Child Psychotherapy-Group Cohesion Scale (TPOCS-GC), which has previously only been used with adult samples, in a youth sample. METHODS: Observers coded 32 sessions from 16 groups with 83 youth aged 8 to 15 years (90.7% European White). Youth had anxiety disorders and received manualized GCBT in community clinics. We examined psychometric properties of the TPOCS-GC and its' construct validity in terms of relations with pretreatment variables, alliance and fidelity during treatment, and post-treatment variables. Group cohesion was measured twice during treatment (early and late). RESULTS: The TPOCS-GC was internally consistent (α = 0.72) and was reliably coded (M ICC = 0.61). Higher clinical severity at pretreatment predicted lower early group cohesion. Higher youth age, higher clinical severity at pretreatment, and higher youth-rated early alliance predicted lower late group cohesion. Higher therapist-rated early alliance predicted higher early group cohesion. Higher therapist-rated late alliance predicted higher late group cohesion. Higher late group cohesion predicted lower clinical severity and higher client treatment satisfaction at post-treatment. Early group cohesion did not predict any post-treatment variables. CONCLUSIONS: A four-item version of the TPOCS-GC can be reliably used in youth GCBT. The TPOCS-GC is distinct from, but associated with, multiple clinical variables.

Effect of early intervention for anxiety on sleep outcomes in adolescents: a randomized trial.

The potential effect of early intervention for anxiety on sleep outcomes was examined in a sample of adolescents with anxiety (N = 313, mean 14.0 years, SD = 0.84, 84% girls, 95.7% Norwegians). Participants were randomized to one of three conditions: a brief or a standard-length cognitive-behavioral group-intervention (GCBT), or a waitlist control-group (WL). Interventions were delivered at schools, during school hours. Adolescents with elevated anxiety were recruited by school health services. Questionnaires on self-reported anxiety symptoms, depressive symptoms, and sleep characteristics were administered at pre- and post-intervention, post-waitlist, and at 1-year follow-up. Adolescents reported reduced insomnia (odds ratio (OR) = 0.42, p < 0.001) and shorter sleep onset latency (d = 0.27, p <  0.001) from pre- to post-intervention. For insomnia, this effect was maintained at 1-year follow-up (OR = 0.54, p = 0.020). However, no effect of GCBT on sleep outcomes was found when comparing GCBT and WL. Also, no difference was found in sleep outcomes between brief and standard-length interventions. Adolescents defined as responders (i.e., having improved much or very much on anxiety after GCBT), did not differ from non-responders regarding sleep outcomes. Thus, anxiety-focused CBT, delivered in groups, showed no effect on sleep outcomes. Strategies specifically targeting sleep problems in adolescents should be included in GCBT when delivered as early intervention for adolescents with elevated anxiety.Trial registry Clinical trial registration: School Based Low-intensity Cognitive Behavioral Intervention for Anxious Youth (LIST); http://clinicalrials.gov/ ; NCT02279251, Date: 11.31. 2014.

Internalizing Symptoms Among Youth in Foster Care: Prevalence and Associations with Exposure to Maltreatment.

Among youth in foster care (N = 303, aged 11-17 years), we investigated prevalence of internalizing symptoms; associations between symptom level and maltreatment types and numbers; and the interaction between gender and maltreatment, on internalizing symptoms. Youth completed Spence Children Anxiety Scale, Short Mood Feelings Questionnaire, and Child and Adolescent Trauma Screen. Compared to community samples, symptom levels above clinical cut-off was more frequent, with social- and generalized anxiety (ES = 0.78-0.88) being most prevalent among youth in foster care. Girls reported more internalizing symptoms (ES = 0.59-0.93). Sexual abuse and neglect were associated with a broader range of internalizing symptoms (ES = 0.35-0.64). Increased incidence of maltreatment was associated with increased levels of symptoms (ES = 0.21-0.22). Associations between maltreatment and symptom level were stronger for girls. This study stresses the importance of broad screening of maltreatment and internalizing symptoms to meet the needs of youth in foster care.

Age and depressive symptoms change predict the 4-year self-concept trajectory for youth after anxiety treatment.

OBJECTIVES: To investigate the self-concept trajectory from before to 4 years after cognitive behavioral therapy (CBT) for youth with anxiety disorders, including predictors. METHODS: Youth with anxiety diagnoses (N = 179; M = 11.5 years, SD = 2.1; 53.6% girls; 46.4% boys) received CBT in community clinics. Self-concept, anxiety/depression symptoms, and diagnostic status were assessed at pre-, post, 1-year, and 4-year posttreatment. RESULTS: Growth curve analyses showed that the self-concept improved significantly over time (d = 0.07 to 0.34). Higher age and a decrease in the depressive symptom trajectory predicted increased self-concept trajectory from baseline to 4 years posttreatment. Not dropping out of treatment also contributed positively to the self-concept trajectory, but not above and beyond decreased depressive symptoms. The correlation between self-concept and depressive symptoms was r = 0.60, indicating these are related but distinct. CONCLUSION: Self-concept can improve after CBT, also long-term. This change appears to primarily be associated with decreased depressive symptoms over time.

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.

Therapist Alliance-Building Behaviors, Alliance, and Outcomes in Cognitive Behavioral Treatment for Youth Anxiety Disorders.

OBJECTIVE: The alliance influences outcomes in CBT for youth anxiety disorders. Thus, knowledge about how therapists can enhance the alliance is needed. METHOD: Seventy-three youth with anxiety diagnoses (M age = 11.5 years, SD = 2.2; range 8 to 15 years; 47.9% boys; 90.4% white-European) participated in 10-session cognitive behavioral therapy in community clinics. Therapist alliance-building behaviors in session 2 was reliably coded with the observer-rated Adolescent Alliance-Building Behavior Scale (Revised) (AABS(R)). Alliance was measured as youth- and therapist-rated alliance, and youth-therapist alliance discrepancy in session 3. Outcomes were diagnostic recovery and anxiety symptom reduction at post-treatment and one-year follow-up, and treatment dropout. We examined the direct effects of alliance-building on alliance, alliance on outcomes, and alliance-building on outcomes in multilevel mediation models, and between- versus within-therapist variance across these effects. RESULTS: The alliance-building behaviors collaborate, present treatment model, and explore motivation positively predicted alliance, whereas actively structuring the session (i.e., dominating) negatively predicted alliance. The alliance-building behaviors attend to experience, collaborate, explore motivation, praise, and support positively predicted outcomes. The alliance-building behaviors present treatment model, express positive expectations, explore cognitions, and support negatively predicted outcomes. The effect of collaborate on symptom reduction was mediated by youth-therapist alliance discrepancy. There was almost zero between-therapist variance in alliance-building, and considerable within-therapist variance. CONCLUSION: Therapist alliance-building behaviors were directly (positively and negatively) associated with alliance and/or outcomes, with only one effect mediated by alliance. Alliance-building behaviors varied far more within therapists (i.e., across clients) than between therapists.

School-based targeted prevention compared to specialist mental health treatment for youth anxiety.

BACKGROUND: The 'FRIENDS for life' program (FRIENDS) is a 10-session cognitive behavioral therapy (CBT) program used for prevention and treatment of youth anxiety. There is discussion about whether FRIENDS is best applied as prevention or as treatment. METHODS: We compared FRIENDS delivered in schools as targeted prevention to a previous specialist mental health clinic trial. The targeted prevention sample (N = 82; Mage  = 11.6 years, SD = 2.1; 75.0% girls) was identified and recruited by school nurses in collaboration with a community psychologist. The clinical sample (N = 88, Mage  = 11.7 years, SD = 2.1; 54.5% girls) was recruited for a randomized controlled trial from community child- and adolescent psychiatric outpatient clinics and was diagnosed with anxiety disorders. RESULTS: Both samples showed significantly reduced anxiety symptoms from baseline to postintervention, with medium mean effect sizes across raters (youths and parents) and timepoints (post; 12-months follow-up). Baseline youth-reported anxiety symptom levels were similar between the samples, whereas parent-reported youth anxiety was higher in the clinical sample. CONCLUSIONS: The study suggests that self-reported anxiety levels may not differ between youth recruited in schools and in clinic settings. The results indicate promising results of the FRIENDS program when delivered in schools by less specialized health personnel from the school health services, as well as when delivered in clinics by trained mental health professionals.

The impact of treatment delivery format on response to cognitive behaviour therapy for preadolescent 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 1,253 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 semistructured clinical interview to assess the presence and severity of DSM-IV psychiatric disorders at preintervention, postintervention 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: In children with primary GAD, SAD or SoAD, there were no significant differences between delivery 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. The difference between individual and group was not significant when follow-up data were examined separately. CONCLUSIONS: Data show 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.

Do clinical experience, formal cognitive behavioural therapy training, adherence, and competence predict outcome in cognitive behavioural therapy for anxiety disorders in youth?

OBJECTIVE: The aim was to investigate whether clinical experience, formal cognitive behavioural therapy (CBT) training, adherence, and competence predict outcome in CBT for anxiety disorders in youth. METHOD: Videotapes (N = 181) from the sessions in a randomized controlled effectiveness trial (Wergeland et al., 2014, Behaviour Research and Therapy, 57, 1-12) comprising youth (N = 182, M age = 11.5 years) with mixed anxiety disorders were assessed for treatment adherence and competence using the Competence and Adherence Scale for CBT for anxiety disorders in youth (Bjaastad et al., 2016, Psychological Assessment, 28, 908-916). Therapists' (N = 17) clinical experience and educational background were assessed. Participants completed a diagnostic interview (Anxiety Disorders Interview Schedule, child and parent versions) and an anxiety symptom measure (Spence Children's Anxiety Scale, child and parent versions) at pretreatment, posttreatment, and 1-year follow-up. RESULTS: Higher therapist adherence was related to better treatment outcomes, whereas number of years of clinical experience and competence was related to worse outcomes. However, these findings were not consistent across informants and the time points for the assessments. Interaction effects suggested that competence among therapists with formal CBT training was related to better patient outcomes. CONCLUSIONS: Therapist adherence, competence, and clinical experience are associated with outcomes of manualized CBT for youth anxiety disorders, but mixed findings indicate the need for more research in this area.

Genetic variation in the endocannabinoid system and response to Cognitive Behavior 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. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Non-replication of the association between 5HTTLPR and response to psychological therapy for child anxiety disorders.

BACKGROUND: We previously reported an association between 5HTTLPR genotype and outcome following cognitive-behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome. AIMS: To replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829). METHOD: Logistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed. RESULTS: There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary anxiety disorder outcomes. CONCLUSIONS: The association between 5HTTLPR genotype and CBT outcome did not replicate. Short-allele homozygotes showed more positive treatment outcomes, but with small, non-significant effects. Future studies would benefit from utilising whole genome approaches and large, homogenous samples.

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.

Therapist-youth agreement on alliance change predicts long-term outcome in CBT for anxiety disorders.

BACKGROUND: In individual cognitive behavioral therapy (ICBT) for youth anxiety disorders, it is unclear whether, and from whose perspective, the alliance predicts outcome. We examined whether youth- and therapist-rated alliance, including level of youth-therapist alliance agreement, predicted outcome in a randomized controlled trial. METHODS: Youth (N = 91, M age = 11.4 years (SD = 2.1), 49.5% boys, 86.8% Caucasian) diagnosed with separation anxiety disorder, social phobia, or generalized anxiety disorder drawn from the ICBT condition of an effectiveness trial were treated with an ICBT program. Youth- and therapist-rated alliance ratings, assessed with the Therapeutic Alliance Scale for Children (TASC-C/T), were collected following session 3 (early) and 7 (late). Early alliance, change in alliance from early to late, and level of youth-therapist agreement on early alliance and alliance change were examined, in relation to outcomes collected at posttreatment and 1-year follow-up. Outcome was defined as primary diagnosis loss and reduction in clinicians' severity ratings (CSR; Anxiety Disorders Interview Schedule; ADIS-C/P) based on youth- and parent-report at posttreatment and follow-up, and youth treatment satisfaction collected at posttreatment (Client Satisfaction Scale; CSS). RESULTS: Early TASC-C scores positively predicted treatment satisfaction at posttreatment. Higher levels of agreement on change in TASC-C and TASC-T scores early to late in treatment predicted diagnosis loss and CSR reduction at follow-up. CONCLUSIONS: Only the level of agreement in alliance change predicted follow-up outcomes in ICBT for youth anxiety disorders. The findings support further examination of the role that youth-therapist alliance discrepancies may play in promoting positive outcomes in ICBT for youth anxiety disorders. Clinical trial number NCT00586586, clinicaltrials.gov.

Mediation Effects of Group Cohesion in Group-Based Cognitive Behavioral Therapy for Youth Anxiety Disorders.

There is limited research on group cohesion as a potential outcome facilitator in group-based cognitive-behavioral treatment (GCBT) for youth. We examined if group cohesion mediated the relation between the temperamental trait behavioral inhibition and posttreatment outcomes following GCBT for youth with anxiety disorders. The sample comprised 88 youth (M age = 11.2 years) from a randomized controlled effectiveness trial. The outcomes were posttreatment clinical severity and treatment satisfaction. Group cohesion fully mediated the relation between behavioral inhibition and posttreatment severity. Higher group cohesion was associated with lower posttreatment clinical severity. There was no significant association between behavioral inhibition and treatment satisfaction, hence no mediation. We conclude that group cohesion is a factor that can be targeted by clinicians to potentially enhance GCBT outcomes.