The Structure of Challenging Parenting Behavior and Associations With Anxiety in Dutch and Australian Children.

Challenging parenting behavior (CPB), a novel construct involving active physical and verbal behaviors that encourage children to push their limits, has been identified as a potential buffer against child anxiety. This study aimed to (a) evaluate the measurement invariance of the Challenging Parenting Behavior Questionnaire (CPBQ4-6) across Dutch and Australian mothers and fathers of preschoolers, (b) examine differences in levels of CPB across mothers and fathers and across countries, and (c) examine whether parents' CPB predicts less child anxiety symptoms and disorders. Participants were 312 families-146 Dutch and 166 Australian-with their 3- to 4-year-old child (55.8% girls). Fathers' and mothers' CPB was measured using the CPBQ4-6, and child anxiety symptoms and presence of anxiety disorders were assessed using maternal reports. Multigroup confirmatory factor analyses revealed equivalence of factor structure and factor loadings (all significant) of the CPBQ4-6 across mothers and fathers and across countries. Evidence of partial scalar invariance indicated that the groups differed on some subscales of the CPBQ4-6. Australian mothers scored lower on the CPB factor than Australian fathers and Dutch parents. Structural equation models showed that CPB predicted fewer child anxiety symptoms and anxiety disorders for all groups. The study confirms that the CPBQ4-6 is appropriate for use with Dutch and Australian parents of preschool-age children and identifies CPB as a multifaceted and coherent construct. The negative relations between CPB and child anxiety suggest that CPB has a protective role in childhood anxiety and is important to examine in future research and interventions.

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.

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.

Predicting outcomes following cognitive behaviour therapy in child anxiety disorders: the influence of genetic, demographic and clinical information.

BACKGROUND: Within a therapeutic gene by environment (G × E) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of G × E data in a way that may be clinically informative. We describe a 'risk-index' approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children. METHOD: DNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross-validation training sets. RESULTS: In predicting treatment outcome, six variables had a minimum mean beta value of 0.5:5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0-8) constructed from these variables had moderate a predictive ability (AUC = .62-.69) in this study. Children scoring high on this index (5-8) were approximately three times as likely to retain their primary anxiety disorder at follow-up as compared with those children scoring 2 or less. CONCLUSION: Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disordered children were identified. Combining these predictors within a risk index could be used to identify which children are less likely to be diagnosis-free following CBT alone and require longer or enhanced treatment. The 'risk-index' approach represents one means of harnessing the translational potential of G × E data.

Targeting risk factors for inhibited preschool children: An anxiety prevention program.

OBJECTIVE: Children with a behaviorally inhibited temperament during early childhood have been shown to have an increased risk for developing anxiety disorders. This study evaluated the efficacy of an anxiety prevention program aimed at reducing the risk of anxiety in behaviorally inhibited preschool children. METHOD: Participants were 86 children aged 41-57 months and their mothers. Children were selected if their mothers reported high levels of child behavioral inhibition on a screening measure. Participants were randomly allocated to a nine-session intervention or a waitlist control condition. Mothers and children both participated in the intervention. RESULTS: At follow-up, the intervention group had significantly fewer clinician-rated child anxiety disorders and fewer mother-reported child anxiety symptoms than at baseline but this change was not significantly different to the change seen in the waitlist control group. CONCLUSIONS: On average, across the course of the study, anxiety decreased in all children irrespective of group. A number of potential reasons for this are discussed along with implications for research and clinical practice.

Early Childhood Predictors of Anxiety in Early Adolescence.

This longitudinal study examined a multitude of early childhood predictors of anxiety symptoms and disorders over an 8-year period. The purpose of the study was to identify early life predictors of anxiety across childhood and early adolescence in a sample of at-risk children. The sample included 202 preschool children initially identified as behaviorally inhibited or uninhibited between the ages of 3 years 2 months and 4 years 5 months. Temperament and familial environment variables were assessed using observation and parent report at baseline. Anxiety symptoms and disorders were assessed using questionnaires and diagnostic interviews at baseline (age 4), and at age 6, 9 and 12 years. In line with our hypotheses, the findings showed that preschool children were more likely to experience anxiety symptoms and disorders over time i) when the child was inhibited, ii) when there was a history of maternal anxiety disorders or iii) when mothers displayed high levels of overinvolvement. Further, the study identified a significant interaction effect between temperament and maternal overvinvolvement such that behaviorally inhibited preschoolers had higher anxiety symptoms at age 12, only in the presence of maternal overinvolvement at age 4. The increased risk of anxiety in inhibited children was mitigated when mothers demonstrated low levels of overinvolvement at age 4. This study provides evidence of both additive and interactive effects of temperament and family environment on the development of anxiety and provides important information for the identification of families who will most likely benefit from targeted early intervention.

Content-specific interpretation biases in clinically anxious children.

Cognitive theories of anxiety suggest that anxious children interpret negatively only those materials specifically related to the content of their anxiety. So far, there are only a few studies available that report on this postulated content-specificity of interpretation processes across different anxiety disorders in children, and most of them focused on social anxiety. Therefore, we examined interpretation bias and its content-specificity in a group of clinically anxious children between the ages of 6-12 years with various anxiety disorders, using an "ambiguous scenarios" task. Children were asked to finish scenarios that were related to either social threat, general threat, or separation threat. In total, 105 clinically anxious children, 21 control children and their mothers were assessed with the ADIS-C/P and the Spence Children's Anxiety Scale. As expected, clinically anxious children provided significantly more negative endings to the scenarios than control children. Within the clinically anxious group, specific interpretation biases were found: Interpretation of scenarios related to social threat, general threat, and separation threat were only predicted by the children's self-reported levels of social anxiety, generalized anxiety, and separation anxiety, respectively. These findings support the content-specificity hypothesis that clinically anxious children display interpretation biases that are specific to fear-relevant stimuli.

The relationship between challenging parenting behaviour and childhood anxiety disorders.

BACKGROUND: This research investigates the relationship between challenging parenting behaviour and childhood anxiety disorders proposed by Bögels and Phares (2008). Challenging parenting behaviour involves the playful encouragement of children to go beyond their own limits, and may decrease children's risk for anxiety (Bögels and Phares, 2008). METHOD: Parents (n=164 mothers and 144 fathers) of 164 children aged between 3.4 and 4.8 years participated in the current study. A multi-method, multi-informant assessment of anxiety was used, incorporating data from diagnostic interviews as well as questionnaire measures. Parents completed self-report measures of their parenting behaviour (n=147 mothers and 138 fathers) and anxiety (n=154 mothers and 143 fathers). Mothers reported on their child's anxiety via questionnaire as well as diagnostic interview (n=156 and 164 respectively). Of these children, 74 met criteria for an anxiety disorder and 90 did not. RESULTS: Fathers engaged in challenging parenting behaviour more often than mothers. Both mothers' and fathers' challenging parenting behaviour was associated with lower report of child anxiety symptoms. However, only mothers' challenging parenting behaviour was found to predict child clinical anxiety diagnosis. LIMITATIONS: Shared method variance from mothers confined the interpretation of these results. Moreover, due to study design, it is not possible to delineate cause and effect. CONCLUSIONS: The finding with respect to maternal challenging parenting behaviour was not anticipated, prompting replication of these results. Future research should investigate the role of challenging parenting behaviour by both caregivers as this may have implications for parenting interventions for anxious children.

Anxiety and Attentional Bias in Preschool-Aged Children: An Eyetracking Study.

Extensive research has examined attentional bias for threat in anxious adults and school-aged children but it is unclear when this anxiety-related bias is first established. This study uses eyetracking technology to assess attentional bias in a sample of 83 children aged 3 or 4 years. Of these, 37 (19 female) met criteria for an anxiety disorder and 46 (30 female) did not. Gaze was recorded during a free-viewing task with angry-neutral face pairs presented for 1250 ms. There was no indication of between-group differences in threat bias, with both anxious and non-anxious groups showing vigilance for angry faces as well as longer dwell times to angry over neutral faces. Importantly, however, the anxious participants spent significantly less time looking at the faces overall, when compared to the non-anxious group. The results suggest that both anxious and non-anxious preschool-aged children preferentially attend to threat but that anxious children may be more avoidant of faces than non-anxious children.

Clinical Predictors of Response to Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders: The Genes for Treatment (GxT) Study.

OBJECTIVE: The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined demographic and clinical predictors of response to CBT. We hypothesized that the child's gender, type of anxiety disorder, initial severity and comorbidity, and parents' psychopathology would significantly predict outcome. METHOD: A sample of 1,519 children 5 to 18 years of age with a primary anxiety diagnosis received CBT across 11 sites. Outcome was defined as response (change in diagnostic severity) and remission (absence of the primary diagnosis) at each time point (posttreatment, 3-, 6-, and/or 12-month follow-up) and analyzed using linear and logistic mixed models. Separate analyses were conducted using data from posttreatment and follow-up assessments to explore the relative importance of predictors at these time points. RESULTS: Individuals with social anxiety disorder (SoAD) had significantly poorer outcomes (poorer response and lower rates of remission) than those with generalized anxiety disorder (GAD). Although individuals with specific phobia (SP) also had poorer outcomes than those with GAD at posttreatment, these differences were not maintained at follow-up. Both comorbid mood and externalizing disorders significantly predicted poorer outcomes at posttreatment and follow-up, whereas self-reported parental psychopathology had little effect on posttreatment outcomes but significantly predicted response (although not remission) at follow-up. CONCLUSION: SoAD, nonanxiety comorbidity, and parental psychopathology were associated with poorer outcomes after CBT. The results highlight the need for enhanced treatments for children at risk for poorer outcomes.

Interpretation bias in preschool children at risk for anxiety: a prospective study.

A story-stem paradigm was used to assess interpretation bias in preschool children. Data were available for 131 children. Interpretation bias, behavioral inhibition (BI), and anxiety were assessed when children were aged between 3 years 2 months and 4 years 5 months. Anxiety was subsequently assessed 12 months, 2 years, and 5 years later. A significant difference in interpretation bias was found between participants who met criteria for an anxiety diagnosis at baseline, with clinically anxious participants more likely to complete the ambiguous story-stems in a threat-related way. Threat interpretations significantly predicted anxiety symptoms at 12-month follow-up, after controlling for baseline symptoms, but did not predict anxiety symptoms or diagnoses at either 2-year or 5-year follow-up. There was little evidence for a relationship between BI and interpretation bias. Overall, the pattern of results was not consistent with the hypothesis that interpretation bias plays a role in the development of anxiety. Instead, some evidence for a role in the maintenance of anxiety over relatively short periods of time was found. The use of a story-stem methodology to assess interpretation bias in young children is discussed along with the theoretical and clinical implications of the findings.