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.

Testing a cognitive behavioural therapy program for anxiety in autistic adolescents: a feasibility study.

BACKGROUND: Autism includes core symptoms affecting general and social development. Up to 60% of autistic adolescents experience co-occurring anxiety disorders negatively influencing educational, social, and general development together with quality of life. A manualised cognitive behavioural therapy (CBT) program 'Cool Kids - Autism Spectrum Adaptation (ASA)' has previously demonstrated efficacy in reducing anxiety in children with co-occurring autism. The current study investigates the feasibility of adapting this program for adolescents. METHODS: Fifteen autistic adolescents, aged 14-17 years, with co-occurring anxiety disorders were enrolled in the study. Outcome measures collected from both adolescents and parents pre-, post-treatment and at 3-month follow-up included participant evaluation of the program, scores from a semi-structured anxiety interview, and questionnaires on anxiety symptoms, life interference, and quality of life. RESULTS: 92% of the families who completed the program found it useful and would recommend it to other families in a similar situation. At follow-up, 55% no longer met the criteria for their primary anxiety diagnosis and 34% of adolescents were free of all anxiety diagnoses. Of the five adolescents who did not attend school before treatment three (60%) had returned to school after treatment. CONCLUSION: This study suggests that the adaptation of the program 'Cool Kids - ASA' into an adolescent version is feasible and has the potential to show good effects thus enhancing the possibility of education, development and independence in future life for this group. Larger RCTs studies are, however, needed to examine the efficacy of the adolescent version.

Cost-effectiveness of a transdiagnostic psychotherapy program for youth with common mental health problems.

OBJECTIVES: Our objective was to evaluate the cost-effectiveness of the transdiagnostic psychotherapy program Mind My Mind (MMM) for youth with common mental health problems using a cost-utility analysis (CUA) framework and data from a randomized controlled trial. Furthermore, we analyzed the impact of the choice of informant for both quality-of-life reporting and preference weights on the Incremental Cost-Effectiveness Ratio (ICER). METHODS: A total of 396 school-aged (6-16 years) youth took part in the 6-month trial carried out in Denmark. CUAs were carried out for the trial period and four one-year extrapolation scenarios. Costs were based on a combination of budget and self-reported costs. Youths and parents were asked to report on the youth's quality-of-life three times during the trial using the Child Health Utility 9D (CHU9D). Parental-reported CHU9D was used in the base case together with preference weights of a youth population. Analyses using self-reported CHU9D and preference weights of an adult population were also carried out. RESULTS: The analysis of the trial period resulted in an ICER of €170,465. The analyses of the one-year scenarios resulted in ICERs between €23,653 and €50,480. The ICER increased by 24% and 71% compared to the base case when using self-reported CHU9D and adult preference weights, respectively. CONCLUSION: The MMM intervention has the potential to be cost-effective, but the ICER is dependent on the duration of the treatment effects. Results varied significantly with the choice of informant and the choice of preference weights indicating that both factors should be considered when assessing CUA involving youth.

Systematic identification and stratification of help-seeking school-aged youth with mental health problems: a novel approach to stage-based stepped-care.

We investigated whether a novel visitation model for school-aged youth with mental health problems based on a stage-based stepped-care approach facilitated a systematic identification and stratification process without problems with equity in access. The visitation model was developed within the context of evaluating a new transdiagnostic early treatment for youth with anxiety, depressive symptoms, and/or behavioural problems. The model aimed to identify youth with mental health problems requiring an intervention, and to stratify the youth into three groups with increasing severity of problems. This was accomplished using a two-phase stratification process involving a web-based assessment and a semi-structured psychopathological interview of the youth and parents. To assess problems with inequity in access, individual-level socioeconomic data were obtained from national registers with data on both the youth participating in the visitation and the background population. Altogether, 573 youth and their parents took part in the visitation process. Seventy-five (13%) youth had mental health problems below the intervention threshold, 396 (69%) were deemed eligible for the early treatment, and 52 (9%) had symptoms of severe mental health problems. Fifty (9%) youth were excluded for other reasons. Eighty percent of the 396 youth eligible for early treatment fulfilled criteria of a mental disorder. The severity of mental health problems highlights the urgent need for a systematic approach. Potential problems in reaching youth of less resourceful parents, and older youth were identified. These findings can help ensure that actions are taken to avoid equity problems in future mental health care implementations.

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.

Coping strategies and anxiety in association with methotrexate-induced nausea in juvenile idiopathic arthritis.

The aim of this study is to investigate whether methotrexate-induced nausea is associated with anxiety or the use of coping strategies in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). This is an observational study of children diagnosed with JIA (ILAR criteria), treated with MTX and aged 9 years or above. MTX-induced nausea was determined by the children's completion of a nausea diary and the parents' completion of the Methotrexate Intolerance Severity Score (MISS). Anxiety was assessed by the Beck Youth Inventories-Anxiety Inventory (BYI-A) and coping strategies were evaluated by an adapted Nausea Coping Questionnaire. Enrolled were 121 children (82 girls: 39 boys) with a median age (IQR) of 13.3 (11.3-15.1) years. The median MTX-dose (IQR) was 9.7 (9.0-10.9) mg/m2/week. The median treatment duration (IQR) was 340 (142-766) days. The MISS was completed for 120 children; 77 children completed the nausea diary for at least 7 days. MTX-induced nausea was present in 61% (73/120) of the children according to the MISS and in 73% (56/77) of the children according to the nausea diary. MTX-induced nausea was associated with a more frequent use of the coping strategy internalizing/catastrophizing (MISS, p = 0.012; diary, p < 0.0001) and higher BYI-A raw scores (diary, p = 0.016). MTX-induced nausea was associated with anxiety and the use of coping strategies in children with JIA. These psychological factors may be part of the mechanism behind the inter-individual variation in the level of nausea to MTX treatment.

Assessment of family functioning in families with a child diagnosed with type 1 diabetes: Validation and clinical relevance of the general functioning subscale of the McMaster family assessment device.

BACKGROUND: Type 1 diabetes (T1D) can have a negative effect on family functioning, which is associated with deterioration in metabolic control. Therefore, a valid tool for assessing family functioning is clinically relevant. We assessed the quality and validity of the Danish general functioning (GF) subscale of the family assessment device (FAD). Additionally, we investigated GF scores among adolescents with T1D and their parents and the relationship between family functioning and background variables, including metabolic control. METHODS: All Danish families with a child diagnosed with T1D (N = 1997) were invited to participate in a web-based survey. In total, 616 adolescents (aged 12-17 years) and 1035 parents (of children aged 2-17 years) responded. The quality and validity of measurements made using the GF subscale were assessed using the Rasch model and graphical log-linear Rasch models (GLLRMs). Differences among GF responses were also assessed using GLLRMs. The relationships between GF scores and background variables were examined by multivariate analyses. RESULTS: A dichotomized version of the GF subscale provided essentially valid measures of family functioning. Furthermore, the GF subscale measured family functioning most accurately in families with worse family functioning than in our population. To accurately characterize family functioning, it is important to take both parent's and adolescent's perceptions into account. Family functioning was associated with glycated hemoglobin (HbA1c) levels, and discrepancies in family functioning were associated with higher HbA1c levels. CONCLUSIONS: A dichotomized GF subscale is useful for assessment of family functioning. Parent's and adolescent's scores should be kept separate. Family functioning is associated with HbA1c levels.

Past and future life stories in adolescents with anxiety disorders: a comparison with community controls.

The ability to tell one's past life story and to imagine one's personal future serves important social and life defining functions like maintaining identity. In the present study, 34 adolescents diagnosed with anxiety disorders (age 9-17) and 34 community based controls wrote stories about their weekend, their past and future life stories and generated cultural life scripts. Cultural life scripts are culturally shared assumptions as to the order and timing of important life events. Adolescents in the anxiety group had less coherent past and future life stories compared to controls. Anxious adolescents also remembered their pasts as emotionally more negative than community controls, despite the fact that both groups described equally many negative experiences from their pasts. Anxious adolescents imagined their futures to consist mainly of positive events, however, they still expected their futures to be less positive than the control group, and their future life stories were more abstract and included fewer cultural life script events than the control group. Weekend stories did not differ in emotional tone and coherence between groups, suggesting that differences in past and future life stories are not due to differences in general narrative ability.

Group-based Cognitive Behavioural Therapy for Anxiety Disorder in Children with Autism Spectrum Disorder: a feasibility study.

Purpose: Autism spectrum disorder (ASD) includes core symptoms that affect general and social development. High risk of developing comorbid disorders such as anxiety is prominent. Up to 60% of children with ASD suffer from anxiety disorders which can negatively influence educational, social and general development together with quality of life. This study is the first to investigate the feasibility of the manualised cognitive behavioural therapy (CBT) group programme 'Cool Kids ASD' for anxiety adapted for children with ASD in a general hospital setting. Methods: Nine children, aged 9-13 years, with ASD and anxiety recruited from a public child psychiatric health clinic were enrolled in the study. Outcome measures were collected from both child and parent pre- and post-treatment and at 3-month follow-up and included scores from a semi-structured anxiety interview, together with questionnaires on anxiety symptoms, life interference, children's automatic thoughts and satisfaction with the programme. Results: Eight out of nine families found the programme useful and would recommend it to other families in a similar situation. Six families attended all 12 sessions in the programme, two missed one session and one family only managed to attend eight sessions. At follow-up, five children were free of all anxiety diagnoses and a further two out of the nine children no longer met the criteria for their primary anxiety diagnosis. Conclusions: This study suggests that the transition of the group programme 'Cool Kids ASD' from University Clinics to standard child psychiatric clinical settings is feasible. Further randomised studies are needed to confirm the efficacy of the programme in a larger sample.

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.

A Danish version of self-efficacy in diabetes self-management: A valid and reliable questionnaire affected by age and sex.

BACKGROUND: Managing the chronic illness type 1 diabetes (T1D) is extremely demanding, especially during adolescence. Self-efficacy is belief in one's own capabilities and this is crucial for diabetes management. Having a valid method for measuring self-efficacy is important. OBJECTIVE: Our aims were to psychometrically validate a Danish version of the self-efficacy in diabetes management (SEDM) questionnaire, and to examine the relationship between background variables and self-efficacy. METHODS: All Danish adolescents with T1D (n = 1075) were invited to participate in our study. In total, 689 agreed to participate and 602 completed the study. Data were collected using a web-based survey. All participants were asked to provide a blood sample for HbA1c measurement. Graphical log-linear Rasch modeling (GLLRM) was used to validate the questionnaire and its reliability was assessed using Monte Carlo simulation. RESULTS: We found the questionnaire to be valid and reliable, but it had a dual structure that suggested a need for 2 separate subscales. One subscale related to practical (SEDM1) and the other to emotional (SEDM2) aspects of diabetes management. Both subscales were targeted toward adolescents with lower self-efficacy and were associated with HbA1c. SEDM1 was influenced by treatment modality and age. In SEDM2 we found an interaction between age and sex. CONCLUSION: The Danish version of the SEDM questionnaire should be divided into two parts, each with a valid and reliable subscale for self-efficacy measurement. The relationship between self-efficacy and age seems to differ between boys and girls.

Psychometric validation of a Danish version of the Obsessive Beliefs Questionnaire - Child Version (OBQ-CV).

AIM: The aim of the study was to examine the psychometric properties of a Danish version of the Obsessive Beliefs Questionnaire - Child Version (OBQ-CV). The OBQ-CV assesses dysfunctional beliefs concerning responsibility/threat estimation, perfectionism/uncertainty, and importance/control of thoughts, which according to cognitive theories are important in the development and maintenance of obsessive-compulsive disorder (OCD). METHODS: The study included a pediatric sample (age 7-17 years) consisting of 57 children and adolescents with OCD, 49 children and adolescents with an anxiety disorder (AD), and 58 typically developing (TD) children and adolescents without a psychiatric diagnosis. All participants completed the OBQ-CV and the Child Behavior Checklist - the School Age Scales (CBCL/6-18). The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) was used to assess OCD symptom severity in the OCD group. RESULTS: Confirmatory factor analyses supported the three-factor structure and thereby the construct validity of the OBQ-CV. Gender was not associated with subscale scores, whereas age influenced the subscale scores differently in the three groups. Reliability analyses showed acceptable to excellent internal consistency and acceptable test-retest reliability of the instrument. There were significant differences between the OCD group and the TD group, supporting the criterion validity. Results on convergent validity were mixed. CONCLUSIONS: Overall, results supported the reliability and validity of the Danish OBQ-CV and thus the use of the questionnaire for future clinical and research purposes.

A confirmative clinimetric analysis of the 36-item Family Assessment Device.

BACKGROUND: The Family Assessment Device (FAD) is a 60-item questionnaire widely used to evaluate self-reported family functioning. However, the factor structure as well as the number of items has been questioned. A shorter and more user-friendly version of the original FAD-scale, the 36-item FAD, has therefore previously been proposed, based on findings in a nonclinical population of adults. AIMS: We aimed in this study to evaluate the brief 36-item version of the FAD in a clinical population. METHODS: Data from a European multinational study, examining factors associated with levels of family functioning in adult cancer patients' families, were used. Both healthy and ill parents completed the 60-item version FAD. The psychometric analyses conducted were Principal Component Analysis and Mokken-analysis. RESULTS: A total of 564 participants were included. Based on the psychometric analysis we confirmed that the 36-item version of the FAD has robust psychometric properties and can be used in clinical populations. CONCLUSIONS: The present analysis confirmed that the 36-item version of the FAD (18 items assessing 'well-being' and 18 items assessing 'dysfunctional' family function) is a brief scale where the summed total score is a valid measure of the dimensions of family functioning. This shorter version of the FAD is, in accordance with the concept of 'measurement-based care', an easy to use scale that could be considered when the aim is to evaluate self-reported family functioning.

Anxious Children and Adolescents Non-responding to CBT: Clinical Predictors and Families' Experiences of Therapy.

The purpose of the study was to examine clinical predictors of non-response to manualized cognitive behaviour therapy (CBT) among youths (children and adolescents) with anxiety disorders, and to explore families' perspective on therapy, using a mixed methods approach. Non-response to manualized group CBT was determined among 106 youths of Danish ethnicity (7-17 years old) with a primary anxiety disorder, identified with the Clinical Global Impression of Improvement Scale at the 3-month follow-up. Twenty-four youths (22.6 %) had not responded to treatment, and a logistic regression analysis revealed that youths with a primary diagnosis of social phobia were seven times more likely not to respond, whereas youths with a comorbid mood disorder were almost four times more likely. Families of non-responding youths with primary social phobia and/or a comorbid mood disorder (n = 15) were interviewed, and data were analysed through interpretative phenomenological analysis. Two superordinate themes emerged: youths were not involved in therapy work, and manualized group format posed challenges to families. The mixed methods approach provided new perspectives on the difficulties that may be encountered by families of non-responding youths with a primary social phobia diagnosis and youths with a comorbid mood disorder during manualized group CBT. Clinical implications related to youths' clinical characteristics, and families' experience and suggestions are drawn. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGES: Youths with an anxiety disorder, who had a primary social phobia diagnosis and those, who had a comorbid mood disorder, were more likely not to respond to manualized group CBT. Parents of those non-responding youths often considered them as motivated to overcome their difficulties, but due to their symptomatology, they were unreceptive, reluctant and ambivalent and therefore not actively involved in therapy. The non-responding youths with social phobia felt evaluated and nervous of what others thought of them in the group. The parents of the non-responding youths with a comorbid mood disorder felt the group format placed restraints on therapists' ability to focus on their individual needs.

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.

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.

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.

A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders.

BACKGROUND: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders. METHODS: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. RESULTS: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively). CONCLUSIONS: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment.

Homework Adherence and Cognitive Behaviour Treatment Outcome for Children and Adolescents with Anxiety Disorders.

BACKGROUND: Homework assignments are considered an essential component for a successful outcome of cognitive behavioural therapy for youths with anxiety disorders. However, only two studies have examined the association between homework adherence and outcome of cognitive behavioural therapy for youths with anxiety disorders. AIMS: The study examined the association between homework adherence and treatment outcome following a generic group cognitive behaviour treatment program (Cool Kids) for anxiety disordered youths and their parents. METHOD: The treatment program was completed by 98 children and adolescents (ages 7-16). Homework adherence was measured as time spent doing homework assignments between each session, reported by youths as well as parents. Outcome criteria consisted of youth-reported anxiety symptoms and clinician rated severity of primary anxiety diagnosis at posttreatment and 3-month follow-up. RESULTS: Results did not support an association between homework adherence and treatment outcome when controlling for pretreatment severity. CONCLUSIONS: The study found no convincing evidence that homework adherence predicted outcome of cognitive behavioural therapy for youths with anxiety disorders. Reasons for divergent findings on homework adherence in cognitive behavioural therapy for youths compared to adults are discussed.

HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). METHODS: Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). RESULTS: Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. CONCLUSIONS: Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.