Behavioral Inhibition and Social Anxiety Disorder as Predictors of Long-Term Outcomes of Cognitive Behavioral Therapy for Youth Anxiety Disorders.

The temperamental trait behavioral inhibition (BI) is related to the development and maintenance of anxiety, particularly much so to social anxiety disorder. We investigated if BI and social anxiety disorder predicted cognitive behavioral therapy (CBT) outcomes for youth anxiety. Youth (N = 179; Mage = 11.6 years) were assessed 4 years following a randomized controlled CBT effectiveness trial. BI was measured by the parent-reported Behavioral Inhibition Questionnaire at baseline. The outcomes were diagnostic recovery, youth- and parent-reported anxiety symptoms, and clinical severity at post-treatment, 1-year, and 4-year follow-up. Having social anxiety disorder negatively predicted diagnostic recovery and predicted higher clinical severity at all assessment points and was the only significant predictor of outcomes at 4-year follow-up. Higher BI negatively predicted diagnostic recovery and predicted higher clinical severity and parent-reported symptom levels at post-treatment and 1-year follow-up, and predicted higher youth-reported anxiety levels at 1-year follow-up. Higher BI was the only predictor of youth- and parent-reported anxiety symptoms. BI and social anxiety disorder seem to be unique predictors of CBT outcomes among youth with anxiety disorders. CBT adaptations may be indicated for youth with high BI and social anxiety disorder.

Anxiety Symptom Trajectories Predict Depression Symptom Trajectories up to Four Years After CBT for Youth Anxiety Disorders.

Long-term data on depression symptoms after cognitive behavioral therapy (CBT) for youth anxiety disorders are scant. We examined depression symptoms up to four years post CBT for anxiety addressing youth age and gender, family social class, and parent mental health as predictors. The sample comprised 179 youth (M age at pre-treatment = 11.5 years; SD = 2.1) in a randomized controlled trial. Clinically assessed anxiety diagnoses and youth and parent-reported anxiety and depression symptoms were measured before, after, and one and four years after CBT. Parent self-reported mental health was measured before CBT. We used regression analyses to determine whether full diagnostic recovery at post-CBT predicted depression trajectories across the four-year assessment period. We used growth curve models to determine whether anxiety trajectories predicted depression trajectories across the four-year assessment period. Youth who lost their anxiety diagnoses after CBT had significantly lower parent-reported depression levels over time, but not lower youth self-reported depression levels. The anxiety symptom trajectory predicted the depression symptom trajectory up to four years post-treatment. There was more explained variance for within-informant (youth-youth; parent-parent) than cross-informants. Being older, female, having lower socio-economic status and parents with poorer mental health were associated with more youth-rated depression over time. However, these demographic predictors were not significant when anxiety symptoms trajectories were added to the models. Successful CBT for anxiety in children is associated with less depression symptoms for as long as four years. Anxiety symptom improvement appears to be a stronger predictor that demographic variables and parent mental health.

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.

Comprehensive Health Assessment for Children in Out-of-Home Care: An Exploratory Study of Service Needs and Mental Health in a Norwegian Population.

A comprehensive model for routine multi-disciplinary health assessment for children in out-of-home care was piloted in a Norwegian region. This paper reports on identified service needs and mental disorders among 196 children (0-17 years) receiving the assessment. Cross-sectional data was extracted from assessment reports. Results show needs across a range of services, with a mean of 2.8 recommended services for children aged 0-6 and 3.3 for children aged 7-17. Mental disorders were identified in 50% of younger children, and 70% of older children. For all children, overall service need was associated with mental disorders, in addition to male gender among younger children. Need for specialized mental health services was associated with mental disorders among younger children and increasing age among older children. The high frequency of service needs and mental disorders illustrate the importance of offering comprehensive health assessments routinely to this high-risk child population and necessitates coordinated service delivery.

Adherence, Competence, and Alliance as Predictors of Long-term Outcomes of Cognitive Behavioral Therapy for Youth Anxiety Disorders.

The present study investigated therapist adherence, therapist competence, and patient-therapist alliance as predictors of long-term outcomes of cognitive behavioral therapy (CBT) for anxiety disorders in youth. Potential differential effects for group versus individual CBT, for therapists with or without formal CBT training, and based on youth symptom severity were examined. Videotapes (n = 181) from treatment sessions in a randomized controlled effectiveness trial comprising youth (N = 170, M age = 11.6 years, SD = 2.1) with anxiety disorders were assessed for therapist adherence and competence. Alliance was rated by therapists and youth. Participants completed a diagnostic interview and an anxiety symptom measure at pre-treatment, post-treatment, one-year follow-up, and long-term follow-up (M = 3.9 years post-treatment, SD = 0.8, range = 2.2-5.9 years). The change in anxiety symptoms or diagnostic status from pre-treatment to long-term follow-up was not significantly related to any predictor variables. However, several interaction effects were found. For loss of principal diagnosis, therapist competence predicted positive outcome when therapist adherence also was high. Adherence was found to predict positive outcome if CBT was provided individually. Therapist-rated alliance was related to both loss of principal diagnosis and loss of all diagnoses when CBT was provided in groups. Interaction effects suggested that therapists displaying both high adherence and high competence produced better long-term outcomes. Further, the alliance may be particularly important for outcomes in group CBT, whereas adherence may be particularly important for outcomes in individual CBT.

Prevalence of psychiatric disorders in Norwegian 10-14-year-olds: Results from a cross-sectional study.

Youth mental health problems is the leading cause of disability worldwide and a major public health concern. Prevalence rates are needed for planning preventive interventions and health care services. We here report Norwegian prevalence estimates for youth mental disorders based on findings from the Bergen Child Study cohort. A web-based psychiatric interview; the Development and Well-Being Assessment, was completed by parents and teachers of 2,043 10-14-year-olds from the city of Bergen, Norway. Post-stratification weights were used to account for selective participation related to parental educational in the estimation of prevalence rates. Prevalence rates are presented for the whole sample and stratified by gender and age. The overall population weighted estimate suggests that 6.93% (95% CI 5.06-9.41) of the children met DSM-IV diagnostic criteria for one or more psychiatric disorders. There were no robust indications of age- or gender-related differences in the prevalence. 11.4% of the children fulfilled criteria for more than one diagnosis. The most common comorbid conditions were ADHD and disruptive disorders. The prevalence of psychiatric disorders was relatively low among Norwegian 10-14-year-olds, compared to published worldwide prevalence estimates. This is in line with estimates from prior studies from the Nordic countries. These findings raise important questions about the origins of different prevalence rates for psychiatric disorders between societies. The findings also illustrate the importance of locally driven epidemiological studies for planning preventative efforts and appropriately scaling mental health services to meet the need of the population.

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.

Parental internalizing symptoms as predictors of anxiety symptoms in clinic-referred children.

BACKGROUND: Mothers' and fathers' internalizing symptoms may influence children's anxiety symptoms differently. OBJECTIVE: To explore the relationship between parental internalizing symptoms and children's anxiety symptoms in a clinical sample of children with anxiety disorders. METHOD: The sample was recruited through community mental health clinics for a randomized controlled anxiety treatment trial. At pre-intervention, children (n = 182), mothers (n = 165), and fathers (n = 72) reported children's anxiety symptoms. Mothers and fathers also reported their own internalizing symptoms. The children were aged 8 to 15 years (M age = 11.5 years, SD = 2.1, 52.2% girls) and all had a diagnosis of separation anxiety, social phobia, and/or generalized anxiety disorder. We examined parental internalizing symptoms as predictors of child anxiety symptoms in multiple regression models. RESULTS: Both mother and father rated internalizing symptoms predicted children's self-rated anxiety levels (adj. R 2 = 22.0%). Mother-rated internalizing symptoms predicted mother-rated anxiety symptoms in children (adj. R 2 = 7.0%). Father-rated internalizing symptoms did not predict father-rated anxiety in children. CONCLUSIONS: Clinicians should incorporate parental level of internalizing symptoms in their case conceptualizations.

Measurement Equivalence and Convergent Validity of a Mental Health Rating Scale.

Emotional and behavioral problems among children and adolescents may be studied using the Strengths and Difficulties Questionnaire, containing five subscales, based on ratings by parents, teachers, or adolescents themselves. We investigate two measurement issues using data from a longitudinal sample of 8,806 participants aged 7 to 9 years and 11 to 13 years from the Bergen Child Study in Bergen, Norway. First, convergent validity of parent and teacher ratings is studied using a multitrait-multimethod approach. Second, longitudinal measurement equivalence is studied using confirmatory factor analysis, which requires us to deal with the considerable attrition. The multitrait-multimethod indicates not only good convergent validity but also considerable method variance for parents and teachers. The reliability and validity of some subscales are relatively low. Attrition analysis indicates that attrition is not missing completely at random, but estimation assuming missing at random makes no real difference. We conclude that assuming missing completely at random is acceptable. Comparing ratings by parents and teachers results in partial scalar equivalence. In addition, all subscales exhibit (partial) longitudinal scalar measurement equivalence. We recommend using latent variable modeling and not summated scales for longitudinal modeling using the Strengths and Difficulties Questionnaire.

DNA methylation changes in infants between 6 and 52 weeks.

Infants undergo extensive developments during their first year of life. Although the biological mechanisms involved are not yet fully understood, changes in the DNA methylation in mammals are believed to play a key role. This study was designed to investigate changes in infant DNA methylation that occurs between 6 and 52 weeks. A total of 214 infant saliva samples from 6 or 52 weeks were assessed using principal component analyses and t-distributed stochastic neighbor-embedding algorithms. Between the two time points, there were clear differences in DNA methylation. To further investigate these findings, paired two-sided student's t-tests were performed. Differently methylated regions were defined as at least two consecutive probes that showed significant differences, with a q-value < 0.01 and a mean difference > 0.2. After correcting for false discovery rates, changes in the DNA methylation levels were found in 42 genes. Of these, 36 genes showed increased and six decreased DNA methylation. The overall DNA methylation changes indicated decreased gene expression. This was surprising because infants undergo such profound developments during their first year of life. The results were evaluated by taking into consideration the extensive development that occurs during pregnancy. During the first year of life, infants have an overall three-fold increase in weight, while the fetus develops from a single cell into a viable infant in 9 months, with an 875-million-fold increase in weight. It is possible that the findings represent a biological slowing mechanism in response to extensive fetal development. In conclusion, our study provides evidence of DNA methylation changes during the first year of life, representing a possible biological slowing mechanism. We encourage future studies of DNA methylation changes in infants to replicate the findings by using a repeated measures model and less stringent criteria to see if the same genes can be found, as well as investigating whether other genes are involved in development during this period.

The utility of the SCAS-C/P to detect specific anxiety disorders among clinically anxious children.

Questionnaire measures offer a time and cost-effective alternative to full diagnostic assessments for identifying and differentiating between potential anxiety disorders and are commonly used in clinical practice. Little is known, however, about the capacity of questionnaire measures to detect specific anxiety disorders in clinically anxious preadolescent children. This study aimed to establish the ability of the Spence Children's Anxiety Scale (SCAS) subscales to identify children with specific anxiety disorders in a large clinic-referred sample (N = 1,438) of children aged 7 to 12 years. We examined the capacity of the Separation Anxiety, Social Phobia, Generalized Anxiety, and Physical Injury Fears (phobias) subscales to discriminate between children with and without the target disorder. We also identified optimal cutoff scores on subscales for accurate identification of children with the corresponding disorder, and examined the contribution of child, mother, and father reports. The Separation Anxiety subscale was able to accurately identify children with separation anxiety disorder, and this was replicated across all 3 reporters. Mother- and father-reported Social Phobia subscales also accurately identified children with social anxiety disorder, although child report was only able to accurately detect social anxiety disorder in girls. Using 2 or more reporters improved the sensitivity of the Separation Anxiety and Social Phobia subscales but reduced specificity. The Generalized Anxiety and Physical Injury Fears subscales failed to accurately identify children with the corresponding disorders. These findings have implications for the potential use of mother-, father-, and child-report SCAS subscales to detect specific disorders in preadolescent children in clinical settings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Prenatal maternal depressive symptoms and infant DNA methylation: a longitudinal epigenome-wide study.

Background: Prenatal maternal stress increases the risk of offspring developmental and psychological difficulties. The biological mechanisms behind these associations are mostly unknown. One explanation suggests that exposure of the fetus to maternal stress may influence DNA methylation. However, this hypothesis is largely based on animal studies, and human studies of candidate genes from single timepoints. Aim: The aim of this study was to investigate if prenatal maternal stress, in the form of maternal depressive symptoms, was associated with variation in genome-wide DNA methylation at two timepoints. Methods: One-hundred and eighty-four mother-child dyads were selected from a population of pregnant women in the Little-in-Norway study. The Edinburgh Postnatal Depression Scale (EPDS) measured maternal depressive symptoms. It was completed by the pregnant mothers between weeks 17 and 32 of gestation. DNA was obtained from infant saliva cells at two timepoints (age 6 weeks and 12 months). DNA methylation was measured in 274 samples from 6 weeks (n = 146) and 12 months (n = 128) using the Illumina Infinium HumanMethylation 450 BeadChip. Linear regression analyses of prenatal maternal depressive symptoms and infant methylation were performed at 6 weeks and 12 months separately, and for both timepoints together using a mixed model. Results: The analyses revealed no significant genome-wide association between maternal depressive symptoms and infant DNA methylation in the separate analyses and for both timepoints together. Conclusions: This sample of pregnant women and their infants living in Norway did not reveal associations between maternal depressive symptoms and infant DNA methylation.

A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders.

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.

Predictors of long-term outcome of CBT for youth with anxiety disorders treated in community clinics.

Cognitive behavioral therapy (CBT) has proven long-term effects in youth with anxiety disorders. However, only a few studies have examined predictors of long-term outcomes of CBT treatment. The present study investigated possible predictors of long-term treatment outcomes in youth with mixed anxiety disorders treated in community mental health clinics. A total of 139 youth (mean age at assessment 15.5 years, range 11-21 years) with a principal diagnosis of separation anxiety disorder, social anxiety disorder, and/or generalized anxiety disorder were evaluated a mean of 3.9 years post-treatment (range 2.2-5.9 years). Outcomes were loss of all inclusion anxiety diagnoses, loss of the principal inclusion anxiety diagnosis, and changes in youth- and parent-rated youth anxiety symptoms. Predictors encompassed youth, parent and demographic factors, and post-treatment recovery. The most consistent finding was that low family social class predicted poorer outcomes. Higher treatment motivation was associated with better outcome whereas a diagnosis of social anxiety was associated with poorer outcome. Identified predictors extend on previous findings from efficacy trials, and the results indicate a need for more specific treatment protocols.

Cognitive behavior therapy for child and adolescent anxiety disorders: an update on recent evidence.

PURPOSE OF REVIEW: To present an updated review of recent studies into the effect of cognitive behavior therapy (CBT) for anxiety disorders in children and adolescents, ways to increase access to therapy, and predictors and moderators of therapy effect. RECENT FINDINGS: The evidence base of CBT for anxiety disorders in children and adolescents continues to grow, demonstrating short and long-term efficacy and effectiveness. However, compared with active control conditions its effect appear to be modest; and a substantial percentage of youth do not show stable long-term remission. Standard CBT is often costly, with high noncompletion rates. New strategies to increase access to effective therapy for the large number of youth with anxiety disorders is therefore of priority. Additionally, there is a need for developing new ways to treat nonresponders, and to identify predictors and moderators of the effects of CBT. SUMMARY: Although there is evidence for the efficacy and effectiveness of CBT for youth with anxiety disorders, there is doubt regarding its superiority over active control comparisons. Long-term outcome is uncertain, as a substantial percentage of youth remains impaired at follow-up. It is essential to develop more cost-efficient strategies to reach youth with anxiety disorders with effective treatments, and to identify early indicators for youth needing additional therapy.

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.

Epidemiological study of child and adolescent psychiatric disorders in Lithuania.

BACKGROUND: From the public health perspective, epidemiological data of child mental health and psychosocial correlates were necessary and very lacking in Lithuanian society that has been undergoing rapid socio-economic change since the past decades. Together with determining the prevalence rates of disorders and assessing the needs for the services, this study has also shifted attention from the highly selective samples of children attending children and adolescent mental health services towards less severe cases of psychopathology as well as different attitudes of parents and teachers. The aim of the first epidemiological study in Lithuania was to identify the prevalence of psychiatric disorders in the community sample of children. METHODS: Child psychiatric disorders were investigated in a representative sample of 3309 children aged 7-16 years (1162 7-10-year-olds and 2147 11-16-year-olds), using a two-phase design with the Lithuanian version of the Strengths and Difficulties Questionnaire (SDQ) in the first screening phase, and the Development and Well-Being Assessment (DAWBA) in the second diagnostic phase. RESULTS: The estimated point prevalence of ICD-10 psychiatric disorders was 13.1% for the total sample (14.0% for the child sample and 12.1% for adolescent sample). The most common groups of disorders were Conduct disorders 6.6% (7.1% for child sample and 6.0% for adolescent sample), Anxiety disorders 5.0% (5.9% for child sample and 6.0% for adolescent sample), with Hyperkinesis being less common 2.0% (2.7% for child sample and 1.2% for adolescent sample). Potential risk factors were related to individual characteristics of the child (gender, poor general health, and stressful life experiences), and the family (single parenthood, foster care, unfavourable family climate, disciplining difficulties, worries related to TV or computer use). CONCLUSIONS: The overall prevalence of youth psychiatric disorders was relatively high in this representative Lithuanian sample compared to Western European countries. The SDQ and DAWBA measures appear useful for the further research and clinical practice in this society.

Long-term effectiveness of cognitive behavioral therapy for youth with anxiety disorders.

Cognitive behavioral therapy (CBT) has demonstrated favorable long-term outcomes in youth with anxiety disorders in efficacy trials. However, long-term outcomes of CBT delivered in a community setting are uncertain. This study examined the long-term outcomes of individual (ICBT) and group CBT (GCBT) in youth with anxiety disorders treated in community mental health clinics. A total of 139 youth (mean age at assessment 15.5 years, range 11-21 years) with a principal diagnosis of separation anxiety disorder (SAD), social anxiety disorder (SOP), and/or generalized anxiety disorder (GAD) were evaluated, on average, 3.9 years post-treatment (range 2.2-5.9 years). Outcomes included loss of all inclusion anxiety diagnoses, loss of the principal anxiety diagnosis and changes in youth- and parent-rated youth anxiety symptoms. At long-term follow-up, there was loss of all inclusion anxiety diagnoses in 53%, loss of the principal anxiety diagnosis in 63% of participants as well as significant reductions in all anxiety symptom measures. No statistical significant differences in outcome were obtained between ICBT and GCBT. Participants with a principal diagnosis of SOP had lower odds for recovery, compared to those with a principal diagnosis of SAD or GAD. In conclusion, outcomes of CBT for youth anxiety disorders delivered in community mental health clinics were improved at nearly 4 years post-treatment, and recovery rates at long-term follow-up were similar to efficacy trials.

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.