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

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

The Youth Anxiety Measure for DSM-5 (YAM-5):Development and First Psychometric Evidence of a New Scale for Assessing Anxiety Disorders Symptoms of Children and Adolescents

The Youth Anxiety Measure for DSM-5 (YAM-5) is a new self- and parent-report questionnaire to assess anxiety disorder symptoms in children and adolescents in terms of the contemporary classification system. International panels of childhood anxiety researchers and clinicians were used to construct a scale consisting of two parts: part one consists of 28 items and measures the major anxiety disorders including separation anxiety disorder, selective mutism, social anxiety disorder, panic disorder, and generalized anxiety disorder, whereas part two contains 22 items that focus on specific phobias and (given its overlap with situational phobias) agoraphobia. In general, the face validity of the new scale was good; most of its items were successfully linked to the intended anxiety disorders. Notable exceptions were the selective mutism items, which were frequently considered as symptoms of social anxiety disorder, and some specific phobia items especially of the natural environment, situational and other type, that were regularly assigned to an incorrect category. A preliminary investigation of the YAM-5 in non-clinical (N = 132) and clinically referred (N = 64) children and adolescents indicated that the measure was easy to complete by youngsters. In addition, support was found for the psychometric qualities of the measure: that is, the internal consistency was good for both parts, as well as for most of the subscales, the parent-child agreement appeared satisfactory, and there was also evidence for the validity of the scale. The YAM-5 holds promise as a tool for assessing anxiety disorder symptoms in children and adolescents

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. Copyright © 2013 John Wiley & Sons, Ltd. The ASICA was developed to repeatedly assess anxiety severity in children. The clinician assesses anxious feelings, avoidant behaviour and anxious thoughts. The ASICA discriminates well between anxious and non-anxious children. The ASICA has good psychometric properties and is treatment sensitive. The ASICA can be used in clinical practice to repeatedly monitor anxiety severity

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

Sensitivity of gray's behavioral inhibition system in clinically anxious and non-anxious children and adolescents

The child version of the Carver and White (1994) BIS/BAS-scales (Muris et al., 2005) was used to assess sensitivity of the Behavioral Inhibition and the Behavioral Activation System in clinically anxious and non-anxious youth (n = 175, ages 8-18 years, 70 boys). Results supported the hypothesis that clinical anxiety is associated with overactivity in the BIS (Gray, 1982). Consistent with the revised Reinforcement Sensitivity Theory (Gray & McNaughton, 2000) the BIS-scale consists of two subscales, one measuring BIS_Anxiety and one measuring FFFS_Fear. BIS-scores were higher in the anxious sample than in the non-anxious sample. BAS-scores were equal. Higher levels of BIS-activity were related with an increase in symptoms of anxiety and depression. BIS-scores were higher in girls than in boys, there were no gender differences in BAS-scores. (C) 2010 Elsevier Ltd. All rights reserve

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 metho

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-C

Severe pediatric obsessive compulsive disorder and co-morbid autistic symptoms: Effectiveness of cognitive behavioral therapy

Clinical consensus exists on the recommendation to add medication to cognitive behavioral therapy (CBT) for children with moderate to severe obsessive compulsive disorder (OCD). However, it has never been examined if CBT monotherapy indeed is less effective for this subgroup. In addition, CBT is often expected to be less suitable in case of an autism spectrum disorder. The aim of the present study was to examine if CBT monotherapy is an effective treatment for children with severe OCD and for children with co-morbid autistic symptoms. Methods: Participants were 58 children (8-18 years) with OCD. They were randomized over two conditions: a waitlist followed by CBT, and directly starting CBT. After CBT, participants were followed during a one-year period. Linear mixed model analyses were performed to examine if severity and autistic symptoms were predictors of treatment effect. Results: Results showed that neither baseline severity, F(2,196.52)=.29, p=.75, nor autistic symptoms, F (1, 182.72)=2.09, p=.15, were predictive of treatment effect. Conclusion: Results suggest that the majority of children with OCD, including children with severe OCD and with autistic symptoms, can be treated effectively with CBT. Therefore, the recommendation to combine CBT and medication for children with moderate to severe OCD may need refinement. (C) 2016 Elsevier Inc. All rights reserve

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 and Wells, 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