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.

Disorder-specific cognitive-behavioral therapy for separation anxiety disorder in young children: a randomized waiting-list-controlled trial.

BACKGROUND: Separation anxiety disorder (SAD) is one of the earliest and most common mental disorders in childhood, and a strong predictor of adult psychopathology. Despite significant progress in psychotherapy research on childhood anxiety disorders, no randomized controlled trial has been conducted with a disorder-specific treatment program for young children suffering from SAD. METHODS: Forty-three children (ages 5-7) with SAD and their parents were assigned to either a 16-session disorder-specific SAD treatment program including parent training and classical cognitive-behavioral therapy (CBT) components, or to a 12-week waiting list group. Categorical and/or continuous data for anxiety, impairment/distress and quality of life were collected at baseline, after treatment/waiting list condition, and at a 4-week follow-up. RESULTS: Intention-to-treat analyses indicate that 76.19% of children allocated to the treatment group definitively no longer fulfilled DSM-IV criteria for SAD at follow-up, compared to 13.64% in the waiting list group. Between 91 and 100% of children rated themselves or were rated by their father, mother or therapist as very much or much improved on the global success rating immediately after treatment. Results indicated large time by treatment condition interaction effect sizes (d = 0.98-1.41) across informants for reduction of distress/avoidance in separation situations after the test for the treatment condition. Further, parents reported significant improvements in impairment/distress in the child's major life domains and the child's quality of life. Treatment gains were maintained at the 4-week follow-up assessment. CONCLUSIONS: Results indicate the short-term efficacy of a disorder-specific treatment approach for SAD, and are among the first to indicate that CBT programs work with young children.

Early predictors of separation anxiety disorder: early stranger anxiety, parental pathology and prenatal factors.

OBJECTIVE: The present study seeks to extend research on the etiology of separation anxiety disorder (SAD) in a German-speaking sample by examining differences between children with SAD and healthy comparisons, using a retrospective-reporting paradigm. METHOD: The sample included 106 children with SAD and 44 healthy children between the ages of 4 and 14 years. Parents completed questionnaires and structured clinical interviews to assess parental pathology, pregnancy variables and strong early stranger anxiety. RESULTS: Children with SAD were more likely than healthy children to have had a phase of stronger stranger anxiety in infancy. Further, early stranger anxiety remained a significant predictor of SAD after controlling for maternal depression. Meaningful effects were not found for the influence of parental age at birth or other pregnancy factors. CONCLUSION: This study provides beginning evidence of the potential predictive value of strong stranger anxiety in distinguishing children with SAD from those with no disorder, above and beyond the influence of parental pathology.

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).

Beliefs regarding child anxiety and parenting competence in parents of children with separation anxiety disorder.

BACKGROUND AND OBJECTIVES: Despite the fact that numerous developmental models have highlighted the role of parental cognitive processes in connection with anxiety disorders in children and adolescents, the role of parents' beliefs about their children and parenting remains largely unexplored. This study investigated the specific association between parental beliefs and child separation anxiety. METHOD: Parents of children with a diagnosis of Separation Anxiety Disorder (SAD) reported on beliefs and expectations related to their child's fears and own parenting competence. To study the potential specificity of relationships, a clinical control group of mothers of children with social phobia (SoP) and a group of mothers of children without a mental disorder (healthy controls, HC) were included. RESULTS: Results indicated that parents of anxious children had significantly higher levels of dysfunctional beliefs than the parents in the HC group. Mothers of children with SAD showed lower levels of parenting self-efficacy than mothers of children with SoP. They also demonstrated lower parenting self-efficacy and satisfaction compared to mothers of healthy children. Parental dysfunctional beliefs about child anxiety and paternal parenting self-efficacy were significantly positively associated with child anxiety. The effects remained significant after controlling for parental anxiety and depression. LIMITATIONS: Due to the cross-sectional design of the study, causality of the found effects cannot be inferred. DISCUSSION: Data suggest that children's anxiety and parents' beliefs about their child's anxiety, coping skills and parenting are strongly associated. Further research is needed to investigate whether addressing parental cognitions in addition to parents' anxiety may improve prevention and intervention of child anxiety.

The efficacy of a family-based cognitive-behavioral treatment for separation anxiety disorder in children aged 8-13: a randomized comparison with a general anxiety program.

BACKGROUND: This randomized controlled trial examines the relative efficacy of a disorder-specific treatment program (TrennungsAngstprogramm Für Familien [TAFF]; English: Separation Anxiety Family Therapy) for children suffering from separation anxiety disorder (SAD) in comparison with a general anxiety program. METHOD: Sixty-four children aged 8-13 with SAD and their parents were assigned either to a 16-session disorder-specific SAD treatment program, including parent training and classical cognitive-behavioral therapy (CBT) components (TAFF), or to a general child-focused 16-week comparison group (Coping Cat [CC]) without any parent training. Diagnoses and parent cognitions were assessed at baseline and at follow-ups. Global success ratings were collected at end of treatment and at follow-up. Ratings for anxiety, impairment/distress, and life quality were collected at Baseline 1, again after a 4-week waiting period, repeatedly throughout treatment, at 4 weeks, and at 1-year follow-up. RESULTS: The response rate (no SAD diagnosis) at 4-week follow-up among the 52 treatment completers was 87.5% vs. 82.1% (TAFF vs. CC; intent-to-treat: 67.7% vs. 69.7%). At 1-year follow-up, the response was 83.3% versus 75% (TAFF vs. CC; intent to treat: 64.5% vs. 63.6%). Differences were nonsignificant. Results from rating scales indicated improvement for both groups across time points and assessment areas, with few between-group differences, and some small effects favoring the TAFF program. Both treatment programs yielded a reduction in parental dysfunctional beliefs. CONCLUSIONS: Results indicate a slight advantage of the TAFF program over a general child-based treatment for SAD. However, these differences were less strong than hypothesized, indicating that the inclusion of parent training does not add large effects to classical child-based CBT in school-age children with SAD. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

DSM-IV criteria for childhood separation anxiety disorder: informant, age, and sex differences.

BACKGROUND: The present study examines frequency of DSM-IV symptom and diagnostic criteria for separation anxiety disorder (SAD) by informant, age, and sex. METHODS: Children aged 4-15 years with a primary DSM-IV diagnosis of SAD (N=106) were assessed using structured diagnostic interviews (Kinder-DIPS; DSM-IV-TR Version). Frequency of DSM-IV symptom and diagnostic criteria were examined as a function of informant and child characteristics, along with impairment and distress ratings. RESULTS: The most frequently reported symptoms were separation-related distress, avoidance of being alone/without an adult and sleeping away from caregivers or from home, with nightmares the least frequently endorsed criterion. Child report did not yield any significant sex or age differences. However, parent report revealed greater reluctance or avoidance of school attendance for girls than boys, and for younger children (<8 years). Parent report indicated greater symptom-related impairment than child report, and the number of symptoms was correlated with impairment based on parent report, and with distress based on child report. CONCLUSIONS: The primary indicators of SAD appear to be separation distress, avoidance of being alone, and sleeping away from caregivers. Findings suggest that parents may be best placed to determine impairment, while children may be the most accurate reporters of more covert internal distress. Implications for clinicians are that reports from multiple informants should be used to gain the most comprehensive information about childhood SAD.