Serotonin transporter [corrected] methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.

Enhanced effects of combined cognitive bias modification and computerised cognitive behaviour therapy on social anxiety

This study examines whether combined cognitive bias modification for interpretative biases (CBM-I) and computerised cognitive behaviour therapy (C-CBT) can produce enhanced positive effects on interpretation biases and social anxiety. Forty socially anxious students were randomly assigned into two conditions, an intervention group (positive CBM-I + C-CBT) or an active control (neutral CBM-I + C-CBT). At pre-test, participants completed measures of social anxiety, interpretative bias, cognitive distortions, and social and work adjustment. They were exposed to 6 × 30 min sessions of web-based interventions including three sessions of either positive or neutral CBM-I and three sessions of C-CBT, one session per day. At post-test and two-week follow-up, participants completed the baseline measures. A combined positive CBM-I + C-CBT produced less negative interpretations of ambiguous situations than neutral CBM-I + C-CBT. The results also showed that both positive CBM-I + C-CBT and neutral CBM-I + C-CBT reduced social anxiety and cognitive distortions as well as improving work and social adjustment. However, greater effect sizes were observed in the positive CBM-I + C-CBT condition than the control. This indicates that adding positive CBM-I to C-CBT enhanced the training effects on social anxiety, cognitive distortions, and social and work adjustment compared to the neutral CBM-I + C-CBT condition.

Integrated motivational interviewing and cognitive behavioural therapy for people with psychosis and comorbid substance misuse: randomised controlled trial

Objectives To evaluate the effectiveness of integrated motivational interviewing and cognitive behaviour therapy in addition to standard care for patients with psychosis and a co-morbid substance use problem. Design Two-centre, open, rater-blind randomised controlled trial Setting UK Secondary Care Participants 327 patients with clinical diagnoses of schizophrenia, schizophreniform or schizoaffective disorder and DSM-IV diagnoses of drug and/or alcohol dependence or abuse Interventions Participants were randomly allocated to integrated motivational interviewing and cognitive behaviour therapy or standard care. Therapy has two phases. Phase one – “motivation building” – concerns engaging the patient, then exploring and resolving ambivalence for change in substance use. Phase two –“Action” – supports and facilitates change using cognitive behavioural approaches. Up to 26 therapy sessions were delivered over one year. Main outcomes The primary outcome was death from any cause or admission to hospital in the 12 months after therapy. Secondary outcomes were frequency and amount of substance use (Timeline Followback), readiness to change, perceived negative consequences of use, psychotic symptom ratings, number and duration of relapses, global assessment of functioning and deliberate self harm, at 12 and 24 months, with additional Timeline Followback assessments at 6 and 18 months. Analysis was by intention-to-treat with robust treatment effect estimates. Results 327 participants were randomised. 326 (99.7%) were assessed on the primary outcome, 246 (75.2%) on main secondary outcomes at 24 months. Regarding the primary outcome, there was no beneficial treatment effect on hospital admissions/ death during follow-up, with 20.2% (33/163) of controls and 23.3% (38/163) of the therapy group deceased or admitted (adjusted odds-ratio 1.16; P= 0.579; 95% confidence interval 0.68 to 1.99). For secondary outcomes there was no treatment effect on frequency of substance use or perceived negative consequences, but a statistically significant effect of therapy on amount used per substance-using day (adjusted odds-ratios: (a) for main substance 1.50; P=0.016; 1.08 to 2.09, (b) all substances 1.48; P=0.017; 1.07 to 2.05). There was a statistically significant treatment effect on readiness to change use at 12 months (adjusted odds-ratio 2.05; P=0.004; 1.26 to 3.31), not maintained at 24 months. There were no treatment effects on assessed clinical outcomes. Conclusions Integrated motivational interviewing and cognitive behaviour therapy for people with psychosis and substance misuse does not improve outcome in terms of hospitalisation, symptom outcomes or functioning. It does result in a reduction in amount of substance use which is maintained over the year’s follow up. Trial registration Current Controlled Trials: ISRCTN14404480

Brief cognitive behavioural therapy for extreme shape concern: an evaluation

Objectives. This study was designed to evaluate a new brief cognitive-behavioural intervention to reduce concerns about body shape. Design. Women with high levels of shape concern (N = 50) were randomly assigned to cognitive behaviour therapy or applied relaxation (AR). Baseline assessments were made and then women received their treatment immediately after this assessment, ('immediate' treatment) or 5 weeks after this assessment, during which time no treatment was given ('delayed' treatment, DT). Methods. Shape concern and related cognitions and emotions were assessed at baseline, post-treatment and at 4 and 12 week follow-up (FU). Results. Immediate treatment was superior to DT in reducing shape concerns, and this difference was maintained at 4 week FU. The cognitive behavioural intervention was more effective than AR in changing shape concern and this difference was largely maintained for 3 months. Conclusions. These initial findings support the further investigation of this brief intervention.

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

Background. Within a therapeutic gene by environment (GxE) 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 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 to 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 or thus require longer or enhanced treatment. The ‘risk-index’ approach represents one means of harnessing the translational potential of G×E data.

Cognitive therapy for anxiety disorders: current status and future directions.

This paper reviews recent theoretical, conceptual and practice developments in cognitive-behaviour therapy (CBT) for anxiety disorders. The empirical status of CBT for anxiety disorders is reviewed and recent advances in the field are outlined. Challenges for the future development of CBT for the anxiety disorders are examined in relation to the efficacy, effectiveness and cost-effectiveness of the approach. It is concluded that the major challenge currently facing CBT for anxiety disorders in the UK is how to meet the increased demand for provision whilst maintaining high levels of efficacy and effectiveness. It is suggested that the creation of an evidence base for the dissemination of CBT needs to become a priority for empirical investigation in order effectively to expand the provision of CBT for anxiety disorders.

A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents

Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings.

Young Children's Ability to Engage in Cognitive Therapy Tasks: Associations With Age and Educational Experience

Abstract. In two linked studies we examined children’s performance on tasks required for participation in cognitive therapy. In Study 1 we piloted some new tasks with children aged 5 to 11 years. In study 2 the effects of IQ, age and educational experience were examined in children aged 5 to 7 years. In study 1, 14 children aged 5 to 11 completed three tasks related to cognitive therapy; generating post-event attributions, naming emotions, and linking thoughts and feelings. Study 2 used a between-subjects design in which 72 children aged 5, 6, or 7 years from two primary schools completed the three tasks and the Block Design and Vocabulary sub-tests from the WISC III or WPPSI-R. Children were tested individually during the school day. All measures were administered on the same occasion. In study 2 administration order of the cognitive therapy task and the WISC III/WPPSI-R were randomized. The majority of children demonstrated some ability on each of the three tasks. In study 2, performance was associated with school and with IQ but not with age. There were no gender differences. Children attending a school with an integrated thinking skills programme and those with a higher 1Q were more successful on the cognitive therapy tasks. These results suggest that many young children could engage in cognitive therapy given age-appropriate materials. The effects of training in relevant meta-cognitive skills on children’s ability to use concepts in CBT may warrant further research. Keywords: Cognitive behaviour therapy, young children, cognitive development

Using computers to teach people with intellectual disabilities to perform some of the tasks used within cognitive behavioural therapy: a randomised experiment

Aims Training has been shown to improve the ability of people with intellectual disabilities (IDs) to perform some cognitive behavioural therapy (CBT) tasks. This study used a computerised training paradigm with the aim of improving the ability of people with IDs to: a) discriminate between behaviours, thoughts and feelings, and b) link situations, thoughts and feelings. Methods Fifty-five people with mild-to-moderate IDs were randomly assigned to a training or attention-control condition in a single-blind mixed experimental design. Computerised tasks assessed the participants’ skills in: (a) discriminating between behaviours, thoughts and feelings (separately and pooled together), and (b) cognitive mediation by selecting appropriate emotions as consequences to given thoughts, and appropriate thoughts as mediators of given emotions. Results Training significantly improved ability to discriminate between behaviours, thoughts and feelings pooled together, compared to the attention-control condition, even when controlling for baseline scores and IQ. Large within-group improvements in the ability to identify behaviours and feelings were observed for the training condition, but not the attention-control group. There were no significant between-group differences in ability to identify thoughts, or on cognitive mediation skills. Conclusions A single session of computerised training can improve the ability of people with IDs to understand and practise CBT tasks relating to behaviours and feelings. There is potential for computerised training to be used as a “primer” for CBT with people with IDs to improve engagement and outcomes, but further development on a specific computerised cognitive mediation task is needed.

Cognitive-behavior therapy for compulsive checking in OCD

There is substantial evidence for the effectiveness of psychological treatments for OCD, and various approaches have been widely recommended. These approaches tend to be characterized by exposure and response prevention (ERP) and also tend to be applied equally to all forms of OCD. Patients/clients (and some therapists) often find ERP to be a difficult treatment, and both dropout and refusal rates are unacceptably high. Based on specific cognitive conceptualizations of different manifestations of OCD, new and refined cognitive treatment methods are now available. The present article describes a specific cognitively based approach to the treatment of compulsive checking.

Feasibility of guided CBT self-help for childhood anxiety disorders in primary care

Anxiety disorders in childhood are common, disabling and run a chronic course. Cognitive Behaviour Therapy (CBT) effective but is expensive and trained therapists are scarce. Guided self-help treatments may be a means of widening access to treatment. This study aimed to examine the feasibility of guided CBT self-help for childhood anxiety disorders in Primary Care, specifically in terms of therapist adherence, patient and therapist satisfaction and clinical gain. Participants were children aged 5-12 years referred to two Primary Child and Adolescent Mental Health Services (PCAMHSs) in Oxfordshire, UK, who met diagnostic criteria for a primary anxiety disorder. Of the 52 eligible children, 41 anxious children were assessed for anxiety severity and interference before and after receiving CBT self-help, delivered via the parent (total therapy time= 5 hours) by Primary Mental Health Workers (PMHWs). Therapy sessions were rated for treatment adherence and patients and PMHWs completed satisfaction questionnaires after treatment completion. Over 80% of therapy sessions were rated at a high level of treatment adherence. Parents and PMHWs reported high satisfaction with the treatment. 61% of the children assessed no longer met criteria for their primary anxiety disorder diagnosis following treatment, and 76% were rated as ‘much’/’very much’ improved on the Clinician’s Global Impression-Improvement scale. There were significant reductions on parent and child report measures of anxiety symptoms, interference, and depression. Preliminary exploration indicated that parental anxiety was associated with child treatment outcome. The findings suggest that guided CBT self-help represents a promising treatment for childhood anxiety in primary care.