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A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders.

ABSTRACT: BACKGROUND:The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders. METHODS:We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. RESULTS:The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively). CONCLUSIONS:Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment.

SUBMITTER: Keers R

PROVIDER: S-EPMC5079103 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders.

Keers Robert R Coleman Jonathan R I JR Lester Kathryn J KJ Roberts Susanna S Breen Gerome G Thastum Mikael M Bögels Susan S Schneider Silvia S Heiervang Einar E Meiser-Stedman Richard R Nauta Maaike M Creswell Cathy C Thirlwall Kerstin K Rapee Ronald M RM Hudson Jennifer L JL Lewis Cathryn C Plomin Robert R Eley Thalia C TC

Psychotherapy and psychosomatics 20160405 3

<h4>Background</h4>The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether ...[more]

PMID: 27043157

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Project description:BackgroundGreater access to evidence-based psychological treatments is needed. This review aimed to evaluate whether internet-delivered psychological treatments for mood and anxiety disorders are efficacious, noninferior to established treatments, safe, and cost-effective for children, adolescents and adults.MethodsWe searched the literature for studies published until March 2013. Randomized controlled trials (RCTs) were considered for the assessment of short-term efficacy and safety and were pooled in meta-analyses. Other designs were also considered for long-term effect and cost-effectiveness. Comparisons against established treatments were evaluated for noninferiority. Two reviewers independently assessed the relevant studies for risk of bias. The quality of the evidence was graded using an international grading system.ResultsA total of 52 relevant RCTs were identified whereof 12 were excluded due to high risk of bias. Five cost-effectiveness studies were identified and three were excluded due to high risk of bias. The included trials mainly evaluated internet-delivered cognitive behavioral therapy (I-CBT) against a waiting list in adult volunteers and 88% were conducted in Sweden or Australia. One trial involved children. For adults, the quality of evidence was graded as moderate for the short-term efficacy of I-CBT vs. waiting list for mild/moderate depression (d = 0.83; 95% CI 0.59, 1.07) and social phobia (d = 0.85; 95% CI 0.66, 1.05), and moderate for no efficacy of internet-delivered attention bias modification vs. sham treatment for social phobia (d = -0.04; 95% CI -0.24, 0.35). The quality of evidence was graded as low/very low for other disorders, interventions, children/adolescents, noninferiority, adverse events, and cost-effectiveness.ConclusionsI-CBT is a viable treatment option for adults with depression and some anxiety disorders who request this treatment modality. Important questions remain before broad implementation can be supported. Future research would benefit from prioritizing adapting treatments to children/adolescents and using noninferiority designs with established forms of treatment.

Project description:BackgroundExperiencing anxiety and depression is very common in people with dementia and mild cognitive impairment (MCI). Psychological interventions have been suggested as a potential treatment for these populations. Current research suggests that people with dementia and MCI have limited opportunities for psychological treatments aimed at improving their well-being. A systematic review of the evidence on their effectiveness is likely to be useful in terms of improving outcomes for patients and for future recommendations for practice.ObjectivesThe main objective of this review was to assess the effectiveness of psychological interventions in reducing anxiety and depression in people with dementia or mild cognitive impairment (MCI).Search methodsWe searched the Cochrane Dementia and Cognitive Improvement Group Specialized Register and additional sources for both published and unpublished data.Selection criteriaWe included randomised controlled trials (RCTs) comparing a psychological intervention with usual care or a placebo intervention (social contact control) in people with dementia or MCI.Data collection and analysisTwo review authors worked independently to select trials, extract data and assess studies for risk of bias, using a data extraction form. We contacted authors when further information was not available from the published articles.Main resultsSix RCTs involving 439 participants with dementia were included in the review, but no studies of participants with MCI were identified. The studies included people with dementia living in the community or in nursing home care and were carried out in several countries. Only one of the studies was classified as low risk of bias. Five studies were at unclear or high risk of bias due to uncertainties around randomisation, blinding and selective reporting of results. The studies used the different psychological approaches of cognitive behavioural therapy (CBT), interpersonal therapy and counselling. Two studies were of multimodal interventions including a specific psychological therapy. The comparison groups received either usual care, attention-control educational programs, diagnostic feedback or services slightly above usual care.Meta-analysis showed a positive effect of psychological treatments on depression (6 trials, 439 participants, standardised mean difference (SMD) -0.22; 95% confidence interval (CI) -0.41 to -0.03, moderate quality evidence) and on clinician-rated anxiety (2 trials, 65 participants, mean difference (MD) -4.57; 95% CI -7.81 to -1.32, low quality evidence), but not on self-rated anxiety (2 trials, SMD 0.05; 95% CI -0.44 to 0.54) or carer-rated anxiety (1 trial, MD -2.40; 95% CI -4.96 to 0.16). Results were compatible with both benefit and harm on the secondary outcomes of patient quality of life, activities of daily living (ADLs), neuropsychiatric symptoms and cognition, or on carers' self-rated depressive symptoms, but most of the studies did not measure these outcomes. There were no reports of adverse events.Authors' conclusionsWe found evidence that psychological interventions added to usual care can reduce symptoms of depression and clinician-rated anxiety for people with dementia. We conclude that psychological interventions have the potential to improve patient well-being. Further high quality studies are needed to investigate which treatments are most effective and to evaluate the effect of psychological interventions in people with MCI.

Project description:BackgroundPathological anxiety is responsible for major functional impairments and resistance to conventional treatments in anxiety disorders (ADs), posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Focal neuromodulation therapies such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) are being developed to treat those disorders.MethodsWe performed a dimensional systematic review and meta-analysis to assess the evidence of the efficacy of TMS, tDCS and DBS in reducing anxiety symptoms across ADs, PTSD and MDD. Reports were identified through systematic searches in PubMed/Medline, Scopus and Cochrane library (inception to November 2020), followed by review according to the PRISMA guidelines. Controlled clinical trials examining the effectiveness of brain stimulation techniques on generic anxiety symptoms in patients with ADs, PTSD or MDD were selected.ResultsNineteen studies (RCTs) met inclusion criteria, which included 589 participants. Overall, focal brain activity modulation interventions were associated with greater reduction of anxiety levels than controls [SMD: -0.56 (95% CI, -0.93 to-0.20, I 2 = 77%]. Subgroup analyses revealed positive effects for TMS across disorders, and of focal neuromodulation in generalized anxiety disorder and PTSD. Rates of clinical responses and remission were higher in the active conditions. However, the risk of bias was high in most studies.ConclusionsThere is moderate quality evidence for the efficacy of neuromodulation in treating pathological anxiety.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=233084, identifier: PROSPERO CRD42021233084. It was submitted on January 29th, 2021, and registered on March 1st, 2021. No amendment was made to the recorded protocol. A change was applied for the subgroup analyses based on target brain regions, we added the putative nature (excitatory/inhibitory) of brain activity modulation.

Dataset Information

A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders.

Publications

A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders.

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