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.

Mediators of cognitive behavioral therapy for anxiety-disordered children and adolescents: cognition, perceived control, and coping.

The purpose is to investigate whether a change in putative mediators (negative and positive thoughts, coping strategies, and perceived control over anxious situations) precedes a change in anxiety symptoms in anxiety-disordered children and adolescents receiving cognitive behavioral therapy (CBT). Participants were 145 Dutch children (8-18 years old, M = 12.5 years, 57% girls) with a primary anxiety disorder. Assessments were completed pretreatment, in-treatment, posttreatment, and at 3-month follow-up. Sequential temporal dependencies between putative mediators and parent- and child-reported anxiety symptoms were investigated in AMOS using longitudinal Latent Difference Score Modeling. During treatment an increase of positive thoughts preceded a decrease in child-reported anxiety symptoms. An increase in three coping strategies (direct problem solving, positive cognitive restructuring, and seeking distraction) preceded a decrease in parent-reported anxiety symptoms. A reciprocal effect was found for perceived control: A decrease in parent-reported anxiety symptoms both preceded and followed an increase in perceived control. Using a longitudinal design, a temporal relationship between several putative mediators and CBT-outcome for anxious children was explored. The results suggest that a change in positive thoughts, but not negative thoughts, and several coping strategies precedes a change in symptom reduction and, therefore, at least partly support theoretical models of anxiety upon which the anxiety intervention is based.

The anxiety severity interview for children and adolescents: an individualized repeated measure of anxiety severity.

The Anxiety Severity Interview for Children and Adolescents (ASICA) was developed for the repeated assessment of the impact of anxiety and control over anxiety symptoms. The ASICA incorporates three main components of anxiety: physical response, avoidant behaviour and anxious thoughts. The objective of this study was to evaluate the psychometric properties of the ASICA in children with anxiety disorder (n = 139, age 8-18 years) and a non-anxious control group (n = 40, age 8-18 years). A confirmatory factor analysis confirmed the intended factor structure. Internal reliability was moderate to good; inter-rater reliability was excellent. Four-week test-retest reliability was good. The ASICA discriminated between anxious and non-anxious children and appeared sensitive to treatment change. A cut-off score of 13 was determined. Convergent validity with anxiety symptoms was moderate; discriminant validity with depressive symptoms was less strong. The results suggest that the ASICA is a reliable instrument that could be used in clinical practice to repeatedly monitor anxiety severity.

Temperament, attentional processes, and anxiety: diverging links between adolescents with and without anxiety disorders?

The present study first examined the links between reactive temperament (negative affectivity), regulative temperament (effortful control [EC]) and internalizing problems in adolescents (12-18 years) with anxiety disorders (ANX; N = 39) and without anxiety disorders (nANX; N = 35). Links differed between ANX and nANX participants. Negative affectivity predicted internalizing problems, with almost no role of EC in nANX, but a protective role of EC was found in ANX youth. Second, we investigated the role of attentional bias as a mediator between temperament and internalizing problems. Strategic threat-related bias was predicted by initial attention and EC, but these relations differed in both groups. In nANX participants, higher initial bias scores were predictive for lower strategic bias scores and higher levels of EC were associated with higher bias scores. In ANX participants, there was almost no effect of initial bias or EC on strategic attention. Internalizing problems were predicted by strategic attention, but again differently in ANX and nANX participants. High strategic bias scores were associated with an increase in anxiety in ANX and a decrease in anxiety in nANX participants.

Automatic evaluations in clinically anxious and nonanxious children and adolescents.

Automatic evaluations of clinically anxious and nonanxious children (n = 40, aged 8-16, 18 girls) were compared using a pictorial performance-based measure of automatic affective associations. Results showed a threat-related evaluation bias in clinically anxious but not in nonanxious children. In anxious participants, automatic evaluations of anxiety-relevant stimuli were more negative than those of negative stimuli. In nonanxious participants, evaluations of negative and anxiety-relevant stimuli did not differ. Furthermore, anxious youth had stronger negative evaluations of anxiety-relevant stimuli than nonanxious children. Automatic evaluations of positive, neutral, and negative stimuli did not differ between groups. Threat-related evaluations were predictive of parent-reported, but not child-reported, anxiety.

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).

An indirect and direct measure of anxiety-related perceived control in children: the Implicit Association Procedure (IAP) and Anxiety Control Questionnaire for Children (ACQ-C).

A perceived lack of control over negative events is assumed central to the development of anxiety disorders. So far, only questionnaires were used to test this theory, but they have several disadvantages. In this study, the Implicit Association Procedure (IAP) was adapted to measure anxiety-related perceived control in an indirect way. IAP data of 33 non-selected children were compared to a direct measure of perceived control, the Anxiety Control Questionnaire for Children (ACQ-C). Results showed that higher anxious children had lower perceived control over anxiety-related events than lower anxious children, on both the indirect and the direct measure.

Evaluating statistical and clinical significance of intervention effects in single-case experimental designs: an SPSS method to analyze univariate data.

Single-case experimental designs are useful methods in clinical research practice to investigate individual client progress. Their proliferation might have been hampered by methodological challenges such as the difficulty applying existing statistical procedures. In this article, we describe a data-analytic method to analyze univariate (i.e., one symptom) single-case data using the common package SPSS. This method can help the clinical researcher to investigate whether an intervention works as compared with a baseline period or another intervention type, and to determine whether symptom improvement is clinically significant. First, we describe the statistical method in a conceptual way and show how it can be implemented in SPSS. Simulation studies were performed to determine the number of observation points required per intervention phase. Second, to illustrate this method and its implications, we present a case study of an adolescent with anxiety disorders treated with cognitive-behavioral therapy techniques in an outpatient psychotherapy clinic, whose symptoms were regularly assessed before each session. We provide a description of the data analyses and results of this case study. Finally, we discuss the advantages and shortcomings of the proposed method.

The time-course of threat processing in children: a temporal dissociation between selective attention and behavioral interference.

Although selective attention to threatening information is an adaptive mechanism, exaggerated attention to threat may be related to anxiety disorders. However, studies examining threat processing in children have obtained mixed findings. In the present study, the time-course of attentional bias for threat and behavioral interference was analyzed in a community sample of 8-18-year-old children (N=33) using a pictorial dot probe task. Threatening and neutral stimuli were shown during 17 ms (masked), 500 ms, and 1250 ms. Results provide preliminary evidence of an automatic attentional bias for threat at 17 ms that persists during later, more controlled stages of information processing (500 and 1250 ms). Furthermore, participants showed a delayed response to threat-containing trials relative to neutral trials in the 500 and 1250 ms condition, which may indicate interference by threat. Together, these results suggest that an attentional bias for threat precedes behavioral interference in children. Furthermore, results indicate that performance in daily life can be temporarily interrupted by the processing of threatening information. In addition, results of earlier studies into selective attention in children using tasks based on behavioral responses may have been confounded by interference effects of threat. For future studies, we recommend to take behavioral interference into account.

Psychometric properties of the Dutch version of the Meta-Cognitions Questionnaire-Adolescent Version (MCQ-A) in non-clinical adolescents and adolescents with obsessive-compulsive disorder.

Although the meta-cognitive model (Wells, 1997, 2000) for obsessive-compulsive disorder (OCD) has clearly influenced research and treatment of OCD, little research has been performed in youth samples. In the present study the psychometric properties of the Dutch Meta-Cognitions Questionnaire-Adolescent Version (MCQ-A; Cartwright-Hatton et al., 2004) were examined in a clinical sample of adolescents with OCD (N = 40, 12-18 years) and a non-clinical sample (N = 317; 12-18 years). Results provided support for the 5-factor structure, and showed fair to good internal consistency and generally good retest reliability. Overall, adolescents with OCD reported more meta-cognitive beliefs than non-clinical adolescents. Several subscales were associated with self-reported obsessive-compulsive symptoms, anxiety and depression, but not with clinician-rated OCD severity. In conclusion, results suggest that the Dutch MCQ-A is a reliable and valid questionnaire to examine meta-cognitive beliefs in adolescents.

Positive thinking in anxiety disordered children reconsidered.

Negatively valenced thoughts are assumed to play a central role in the development and maintenance of anxiety. However, the role of positive thoughts in anxiety is rather unclear. In the current study we examined the role of negative and positive self-statements in the anxiety level of anxious and non-anxious children. Participants were 139 anxiety disordered children and 293 non-anxious children (8-18 years). Compared to non-anxious children, anxious children reported more negative thoughts, less positive thoughts and lower State of Mind (SOM) ratios (ratio of positive to negative thoughts). Negative thoughts and SOM ratios were the strongest predictors of anxiety level in anxious children; whereas both negative and positive thoughts were the strongest predictors of anxiety level in non-anxious children. To conclude, a lack of positive thoughts might be more than just an epiphenomenon of anxiety level and might deserve a place in the cognitive model of anxiety.

Perceived control in clinically anxious and non-anxious children indirectly measured with the Implicit Association Procedure (IAP).

BACKGROUND: Perceived control is thought to play an important role in the development and maintenance of anxiety disorders in children. The objective of the present study was to further investigate the Perceived Control Implicit Association Procedure (IAP, Hogendoorn et al., 2008) as an indirect measure of perceived control in children. METHODS: The IAP was completed by 136 anxiety disordered children (aged 8-18 years old, M = 12.51) and 31 non-selected children (8-15 years old, M = 11.65). A second control group of 38 non-selected children (aged 8-18 years old, M = 12.08) was used to validate the pictorial stimuli in the computer task. RESULTS: First, children were able to correctly classify the pictures into Control and No control categories. Second, as predicted, anxious children reported less perceived control than the control group on both the direct measure (the ACQ-C) and the indirect measure (IAP). For the No Control score however, this was only the case for children younger than twelve years old. Third, test-retest correlation in the anxious group was fair to good (ICCs .57-.58). CONCLUSIONS: These results suggest that the perceived control IAP is still quite experimental, but could be an interesting departure point for future research on perceived control in children.

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

To improve research in cognitive theories of childhood OCD, a child version of the Obsessive Beliefs Questionnaire (OBQ-CV) has been developed (Coles et al., 2010). In the present study, psychometric properties of the Dutch OBQ-CV were examined in a community sample (N=547; 8-18 years) and an OCD sample (N=67; 8-18 years). Results revealed good internal consistency and adequate retest reliability (retest interval 7-21 weeks and 6-12 weeks, respectively). Children with OCD reported more beliefs than non-clinical children. Obsessive beliefs were related to self-reported OCD symptoms, but not to clinician-rated OCD severity. Beliefs were also related to anxiety and depression. This is the first study examining the factor structure of the OBQ-CV. Confirmatory factor analyses revealed best fit for four factors representing Perfectionism/Certainty, Importance/Control of Thoughts, Responsibility, and Threat, and a higher-order factor. This is in line with results from adult samples. These results support the reliability and validity of the Dutch OBQ-CV.

Measuring Negative and Positive Thoughts in Children: An Adaptation of the Children's Automatic Thoughts Scale (CATS).

The aim of this study is to describe the factor structure and psychometric properties of an extended version of the Children's Automatic Thoughts Scale (CATS), the CATS-Negative/Positive (CATS-N/P). The CATS was originally designed to assess negative self-statements in children and adolescents. However, positive thoughts also play a major role in childhood disorders such as anxiety and depression. Therefore, positive self-statements were added to the CATS. The CATS-N/P was administered to a community sample of 554 children aged 8-18 years. The results of a confirmatory factor analysis revealed that the positive self-statements formed a separate and psychometrically sound factor. Internal and short-term test-retest reliability was good. Boys reported more hostile and positive thoughts than girls; and younger children reported more negative thoughts concerning physical threat, social threat, and failure than older children. In conclusion, the results of the current study support the use of the CATS-N/P for the measurement of positive and negative thoughts in children. The application of the CATS-N/P can facilitate further research on cognitive factors in different childhood disorders.