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Genetics of response to cognitive behavior therapy in adults with major depression: a preliminary report.

ABSTRACT: Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primary outcome score was measured using the Montgomery Åsberg Depression Rating Scale-Self Rated. Single-nucleotide polymorphism genotyping arrays were used to calculate the genomic risk scores based on large genetic studies of six phenotypes: major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intelligence, and educational attainment. Linear mixed-effect models were used to test the relationships between the six genetic risk scores and cognitive behavior therapy outcome. Our analyses yielded one significant interaction effect (B = 0.09, p < 0.001): the autism spectrum disorder genetic risk score correlated with Montgomery Åsberg Depression Rating Scale-Self Rated changes during treatment, and the higher the autism spectrum disorder genetic load, the less the depressive symptoms decreased over time. The genetic risk scores for the other psychiatric and cognitive traits were not related to depressive symptom severity or change over time. Our preliminary results indicated, as expected, that the genomics of the response of patients with major depression to cognitive behavior therapy were complex and that future efforts should aim to maximize sample size and limit subject heterogeneity in order to gain a better understanding of the use of genetic risk factors to predict treatment outcome.

SUBMITTER: Andersson E

PROVIDER: S-EPMC6477793 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Genetics of response to cognitive behavior therapy in adults with major depression: a preliminary report.

Andersson Evelyn E Crowley James J JJ Lindefors Nils N Ljótsson Brjánn B Hedman-Lagerlöf Erik E Boberg Julia J El Alaoui Samir S Karlsson Robert R Lu Yi Y Mattheisen Manuel M Kähler Anna K AK Svanborg Cecilia C Mataix-Cols David D Mattsson Simon S Forsell Erik E Kaldo Viktor V Schalling Martin M Lavebratt Catharina C Sullivan Patrick F PF Rück Christian C

Molecular psychiatry 20190401 4

Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primar ...[more]

PMID: 30410065

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Project description:ObjectivesAntidepressants have limited efficacy in older adults with depression and cognitive impairment, and psychosocial interventions for this population have been inadequately investigated. Problem Adaptation Therapy (PATH) is a psychosocial intervention for older adults with major depression, cognitive impairment, and disability.DesignThis study tests the efficacy of PATH versus Supportive Therapy for Cognitively Impaired Older Adults (ST-CI) in reducing depression (Montgamery Asberg Depression Rating Scale [MADRS]) and disability (World Health Organization Disability Assessments Schedule-II [WHODAS-II]) and improving cognitive outcomes (Mini Mental State Examination [MMSE]) over 24 weeks (12 weeks of treatment and 12-week post-treatment follow-up).SettingParticipants were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry. Both interventions and all research assessments were conducted at home.ParticipantsThirty-five older adults (age ≥ 65 years) with major depression and cognitive impairment no dementia (CIND).InterventionsPATH aims to increase emotion regulation by incorporating a problem-solving approach, teaching compensatory strategies, and inviting caregiver participation. Supportive Therapy aims to facilitate the expression of affect, as well as promote empathy.MeasurementsDepression was measured using the MADRS, disability using the WHODAS-II, and cognition using the MMSE.ResultsPATH participants showed significantly greater reduction in MADRS total score (7.04 points at 24 weeks, treatment group by time interaction: F[1,24.4] = 7.61, p = 0.0108), greater improvement in MMSE total score (2.30 points at 24 weeks, treatment group by time interaction: F[1,39.8] = 13.31, p = 0.0008), and greater improvement in WHODAS-II total score (2.95 points at 24 weeks, treatment group by time interaction: F[1,89] = 4.93, p = 0.0290) than ST-CI participants over the 24-week period.ConclusionsPATH participants had better depression, cognitive, and disability outcomes than ST-CI participants over 6 months. PATH may provide relief to depressed older adults with CIND who currently have limited treatment options.

Project description:In the last forty years therapy outcomes for depression have remained the same with approximately 50% of patients responding to treatments. Advances are urgently required. We hypothesised that a recent treatment, metacognitive therapy (MCT), might be more effective, by targeting mental control processes that directly contribute to depression. We assessed the clinical efficacy of MCT compared to current best psychotherapy practice, CBT, in adults with major depressive disorder. A parallel randomized single-blind trial was conducted in a primary care outpatient setting. This trial is registered with the ISCRTN registry, number ISRCTN82799488. In total 174 adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder were eligible and consented to take part. 85 were randomly allocated to MCT and 89 to CBT. Randomisation was performed independently following pre-treatment assessment and was stratified for severity of depression (low?<?20 vs high?>?=20) on the Hamilton Depression Rating Scale (HDRS) and on sex (male/female). Assessors and trial statisticians were blind to treatment allocation. Each treatment arm consisted of up to 24 sessions of up to 60?minutes each, delivered by trained clinical psychologists. The co-primary outcome measures were assessor rated symptom severity on the HDRS and self-reported symptom severity on the Beck Depression Inventory II (BDI-II) at post treatment. Secondary outcomes were scores six months post treatment on these measures and a range of symptom and mechanism variables. A key trial design feature was that each treatment was implemented to maximize individual patient benefit; hence time under therapy and number of sessions delivered could vary. Treated groups in the trial were very similar on most baseline characteristics. Data were analyzed on the basis of intention to treat (ITT). No differences were found on the HDRS at post treatment or follow-up (-0.95 [-2.88 to 0.98], p?=?0.336; and -1.61 [-3.65 to 0.43], p?=?0.122), but floor effects on this outcome were high. However, a significant difference favouring MCT was found on the BDI-II at post treatment (-5.49 [95% CI -8.90 to -2.08], p?=?0.002), which was maintained at six-month follow-up (-4.64 [-8.21 to -1.06], p?=?0.011). Following MCT 74% of patients compared with 52% in CBT met formal criteria for recovery on the BDI-II at post treatment (odds-ratio=2.42 [1.20 to 4.92], p?=?0.014). At follow-up the proportions were 74% compared to 56% recovery (odds-ratio=2.19 [1.05 to 4.54], p?=?0.036). Significant differences favouring MCT, also maintained over time, were observed for most secondary outcomes. The results were robust against controlling for time under therapy and when outcomes were assessed at a common 90 day mid-term time-point. Limitations of the study include the use of only two therapists where one treated 69% of patients, possible allegiance effects as the study was conducted in an established CBT clinic and the chief investigator is the originator of MCT and group differences in time under therapy. Never the less evidence from this study suggests that MCT had considerable beneficial effects in treating depression that may exceed CBT.

Project description:IMPORTANCE:Problem adaptation therapy (PATH) is a treatment for older adults with major depression, cognitive impairment (from mild cognitive deficits to moderate dementia), and disability. Antidepressants have limited efficacy in this population and psychosocial interventions are inadequately investigated. OBJECTIVE:To test the efficacy of 12-week PATH vs supportive therapy for cognitively impaired patients (ST-CI) in reducing depression and disability in 74 older adults with major depression, cognitive impairment, and disability. DESIGN, SETTING, AND PARTICIPANTS:A randomized clinical trial at the Weill Cornell Institute of Geriatric Psychiatry from April 1, 2006, to September 31, 2011. Interventions were administered at the participants' homes. Participants included 74 older individuals (age ? 65 years) with major depression and cognitive impairment to the level of moderate dementia. They were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry and were randomly assigned to 12 weekly sessions of PATH or ST-CI (14.8% attrition rate). INTERVENTIONS:Home-delivered PATH vs home-delivered ST-CI. Problem adaptation therapy integrates a problem-solving approach with compensatory strategies, environmental adaptations, and caregiver participation to improve patients' emotion regulation. Supportive therapy for cognitively impaired patients focuses on expression of affect, understanding, and empathy. MAIN OUTCOMES AND MEASURES:Mixed-effects models for longitudinal data compared the efficacy of PATH with that of ST-CI in reducing depression (Montgomery-Asberg Depression Rating Scale) and disability (World Health Organization Disability Assessment Schedule II) during 12 weeks of treatment. RESULTS:Participants in PATH had significantly greater reduction in depression (Cohen d, 0.60; 95% CI, 0.13-1.06; treatment × time, F(1,179) = 8.03; P =?.005) and disability (Cohen d, 0.67; 95% CI, 0.20-1.14; treatment × time, F(1,169) = 14.86; P =?.001) than ST-CI participants during the 12-week period (primary outcomes). Furthermore, PATH participants had significantly greater depression remission rates than ST-CI participants (37.84% vs 13.51%; ?(2) = 5.74; P =?.02; number needed to treat = 4.11) (secondary outcome). CONCLUSIONS AND RELEVANCE:Problem adaptation therapy was more efficacious than ST-CI in reducing depression and disability. Problem adaptation therapy may provide relief to a large group of depressed and cognitively impaired older adults who have few treatment options. TRIALS REGISTRATION:Clinicaltrials.gov Identifier: NCT00368940.

Project description:ImportanceCognitive behavior therapy (CBT) has been shown to be effective in the treatment of acute depression. However, whether CBT can be effectively delivered in individual, group, telephone-administered, guided self-help, and unguided self-help formats remains unclear.ObjectiveTo examine the most effective delivery format for CBT via a network meta-analysis.Data sourcesA database updated yearly from PubMed, PsycINFO, Embase, and the Cochrane Library. Literature search dates encompassed January 1, 1966, to January 1, 2018.Study selectionRandomized clinical trials of CBT for adult depression. The 5 treatment formats were compared with each other and the control conditions (waiting list, care as usual, and pill placebo).Data extraction and synthesisPRISMA guidelines were used when extracting data and assessing data quality. Data were pooled using a random-effects model. Pairwise and network meta-analyses were conducted.Main outcomes and measuresSeverity of depression and acceptability of the treatment formats.ResultsA total of 155 trials with 15 191 participants compared 5 CBT delivery formats with 2 control conditions. In half of the studies (78 [50.3%]), patients met the criteria for a depressive disorder; in the other half (77 [49.7%]), participants scored above the cutoff point on a self-report measure. The effectiveness of individual, group, telephone, and guided self-help CBT did not differ statistically significantly from each other. These formats were statistically significantly more effective than the waiting list (standardized mean differences [SMDs], 0.87-1.02) and care as usual (SMDs, 0.47-0.72) control conditions as well as the unguided self-help CBT (SMDs, 0.34-0.59). In terms of acceptability (dropout for any reason), individual (relative risk [RR] = 1.44; 95% CI, 1.09-1.89) and group (RR = 1.38; 95% CI, 1.06-1.80) CBT were significantly better than guided self-help. Guided self-help was also less acceptable than being on a waiting list (RR = 0.63; 95% CI, 0.52-0.75) and care as usual (RR = 0.72; 95% CI, 0.57-0.90). Sensitivity analyses supported the overall findings.Conclusions and relevanceFor acute symptoms of depression, group, telephone, and guided self-help treatment formats appeared to be effective interventions, which may be considered as alternatives to individual CBT; although there were few indications of significant differences in efficacy between treatments with human support, guided self-help CBT may be less acceptable for patients than individual, group, or telephone formats.

Project description:Depressive disorders (DDs) are one of the most widespread forms of psychiatric pathology. According to the World Health Organization, about 350 million people in the world are affected by this condition. Family and twin studies have demonstrated that the contribution of genetic factors to the risk of the onset of DDs is quite large. Various methodological approaches (analysis of candidate genes, genome-wide association analysis, genome-wide sequencing) have been used, and a large number of the associations between genes and different clinical DD variants and DD subphenotypes have been published. However, in most cases, these associations have not been confirmed in replication studies, and only a small number of genes have been proven to be associated with DD development risk. To ascertain the role of genetic factors in DD pathogenesis, further investigations of the relevant conditions are required. Special consideration should be given to the polygenic characteristics noted in whole-genome studies of the heritability of the disorder without a pronounced effect of the major gene. These observations accentuate the relevance of the analysis of gene-interaction roles in DD development and progression. It is important that association studies of the inherited variants of the genome should be supported by analysis of dynamic changes during DD progression. Epigenetic changes that cause modifications of a gene's functional state without changing its coding sequence are of primary interest. However, the opportunities for studying changes in the epigenome, transcriptome, and proteome during DD are limited by the nature of the disease and the need for brain tissue analysis, which is possible only postmortem. Therefore, any association studies between DD pathogenesis and epigenetic factors must be supplemented through the use of different animal models of depression. A threefold approach comprising the combination of gene association studies, assessment of the epigenetic state in DD patients, and analysis of different "omic" changes in animal depression models will make it possible to evaluate the contribution of genetic, epigenetic, and environmental factors to the development of different forms of depression and to help develop ways to decrease the risk of depression and improve the treatment of DD.

Project description:BACKGROUND:Digital mental health interventions offer a scalable solution that reduces barriers to seeking care for clinical depression and anxiety. OBJECTIVE:We aimed to examine the effectiveness of a 12-week therapist supported, app-based cognitive behavioral therapy program in improving symptoms of depression and anxiety within 9 months. METHODS:A total of 323 participants with mild to moderately severe depression or anxiety were enrolled in a 12-week digital cognitive behavior therapy program. The analysis was restricted to participants who provided at least one follow-up assessment after baseline. As a result, 146 participants (45.2%) were included in the analysis-74 (50.7%) participants completed assessments at 3 months, 31 participants (21.2%) completed assessments at 6 months, and 21 participants (14.4%) completed assessments at 9 months. The program included structured lessons and tools (ie, exercises and practices) as well as one-on-one weekly video counseling sessions with a licensed therapist for 12 weeks and monthly check-in sessions for 1 year. The clinically validated Patient Health Questionnaire (PHQ-8) and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety, respectively. Linear mixed-effects modeling was employed to examine changes in depression and anxiety over time. RESULTS:We observed a significant positive effect of program time on improvement in depression (?=-0.12, P<.001) and anxiety scores (?=-0.10, P<.001). At the end of the 12-week intervention, we observed an average reduction of 3.76 points (95% CI -4.76 to -2.76) in PHQ-8 scores. Further reductions in depression were seen at program month 6 (4.75-point reduction, 95% CI -6.61 to -2.88) and program month 9 (6.42-point reduction, 95% CI -8.66 to -6.55, P<.001). A similar pattern of improvement emerged for anxiety, with a 3.17-point reduction at the end of the 12-week intervention (95% CI -4.21 to -2.13). These improvements were maintained at program month 6 (4.87-point reduction, 95% CI -6.85 to -2.87) and program month 9 (5.19-point, 95% -6.85 to 4.81). In addition, greater program engagement during the first 12 weeks predicted a greater reduction in depression (?=-0.29, P<.001). CONCLUSIONS:The results suggest that digital interventions can support sustained and clinically meaningful improvements in depression and anxiety. Furthermore, it appears that strong initial digital mental health intervention engagement may facilitate this effect. However, the study was limited by postintervention participant attrition as well as the retrospective observational study design.

Dataset Information

Genetics of response to cognitive behavior therapy in adults with major depression: a preliminary report.

Publications

Genetics of response to cognitive behavior therapy in adults with major depression: a preliminary report.

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