A transdiagnostic meta-analysis of acute augmentations to psychological therapy.

At least half of all patients with mental health disorders do not respond adequately to psychological therapy. Acutely enhancing particular biological or psychological processes during psychological therapy may improve treatment outcomes. However, previous studies are confined to specific augmentation approaches, typically assessed within single diagnostic categories. Our objective was to assess to what degree acute augmentations of psychological therapy reduce psychiatric symptoms and estimate effect sizes of augmentation types (for example, brain stimulation or psychedelics). We searched Medline, PsycINFO and Embase for controlled studies published between database inception and 25 May 2022. We conducted a preregistered random-effects meta-analysis (PROSPERO CRD42021236403). We identified 108 studies (N = 5,889). Acute augmentation significantly reduced the severity of mental health problems (Hedges' g = -0.27, 95% CI: [-0.36, -0.18]; P < 0.0001), particularly for the transdiagnostic dimensions 'Fear' and 'Distress'. This result survived a trim-and-fill analysis to account for publication bias. Subgroup analyses revealed that pharmacological, psychological and somatic augmentations were effective, but to varying degrees. Acute augmentation approaches are a promising route to improve outcomes from psychological therapy.

Association Between a Directly Translated Cognitive Measure of Negative Bias and Self-reported Psychiatric Symptoms.

BACKGROUND: Negative interpretation biases are thought to be core symptoms of mood and anxiety disorders. However, prior work using cognitive tasks to measure such biases is largely restricted to case-control group studies, which cannot be used for inference about individuals without considerable additional validation. Moreover, very few measures are fully translational (i.e., can be used across animals and humans in treatment-development pipelines). This investigation aimed to produce the first measure of negative cognitive biases that is both translational and sensitive to individual differences, and then to determine which specific self-reported psychiatric symptoms are related to bias. METHODS: A total of 1060 (n = 990 complete) participants performed a cognitive task of negative bias along with psychiatric symptom questionnaires. We tested the hypothesis that individual levels of mood and anxiety disorder symptomatology would covary positively with negative bias on the cognitive task using a combination of computational modeling of behavior, confirmatory factor analysis, exploratory factor analysis, and structural equation modeling. RESULTS: Participants with higher depression symptoms (ß = -0.16, p = .017) who were older (ß = -0.11, p = .001) and had lower IQ (ß = 0.14, p < .001) showed greater negative bias. Confirmatory factor analysis and structural equation modeling suggested that no other psychiatric symptom (or transdiagnostic latent factor) covaried with task performance over and above the effect of depression, while exploratory factor analysis suggested combining depression/anxiety symptoms in a single latent factor. Generating groups using symptom cutoffs or latent mixture modeling recapitulated our prior case-control findings. CONCLUSIONS: This measure, which uniquely spans both the clinical group-to-individual and preclinical animal-to-human generalizability gaps, can be used to measure individual differences in depression vulnerability for translational treatment-development pipelines.

Converging evidence for enduring perceptions of low social status in individuals in remission from depression.

BACKGROUND: The risk of depressive relapse and recurrence is associated with social risk factors that may be amplified by a submissive socio-cognitive profile. METHODS: In Study 1 we aimed to identify perceptions of low social status in a community sample (N = 613) with a self-reported history of mental health difficulties (n = 232) and, more specifically in Study 2 (N = 122), in individuals in clinical remission from depression (n = 18), relative to a never-depressed control group (n = 64), and relative to a group experiencing a current depressive episode (n = 40). RESULTS: In Study 1, a total of 225 of the 232 participants in the self-reported mental health difficulties group opted to provide further information regarding their mental health history, of whom 153 (68%) reported a history of anxiety, 168 (74.7%) reported a history of depression, and 13 (5.8%) reported an unspecified mental health history. Elevated depressive symptoms were associated with perceptions of low social status which significantly differed between individuals with and without a self-reported history of mental health difficulties. In Study 2 we found enduring perceptions of low social status in remitted depressed individuals. LIMITATIONS: We were unable to discern between historical or current clinical diagnosis in the community sample of Study 1, as we were reliant on self-report. We were unable to explore the effects of medication or causal relationships between depressive symptoms and social status as the studies were cross-sectional in nature. CONCLUSIONS: These findings suggest that evolutionarily rooted socio-cognitive profiles could impact affiliative processes and may confer increased vulnerability to future depressive episodes.

A randomized, controlled proof-of-concept trial evaluating durable effects of memory flexibility training (MemFlex) on autobiographical memory distortions and on relapse of recurrent major depressive disorder over 12 months.

Low-intensity psychological interventions that target cognitive risk factors for depressive relapse may improve access to relapse prevention programs and thereby reduce subsequent risk. This study provides the first evaluation of an autobiographical memory-based intervention for relapse prevention, to establish whether memory-training programs that are efficacious for acute depression may also aid those currently in remission. We also provide the longest follow-up to-date of the effects of autobiographical memory training on autobiographical memory processes themselves. This pre-registered randomized-controlled proof-of-concept trial (N = 74) compared an autobiographical Memory Flexibility (MemFlex) intervention to Psychoeducation about cognitive-behavioral mechanisms which maintain depression. Both interventions were primarily self-guided, and delivered via paper workbooks completed over four weeks. The key cognitive outcome was ability to retrieve and alternate between specific and general autobiographical memories. Co-primary clinical outcomes were time until depressive relapse and depression-free days in the twelve-months following intervention. Results indicated a small-moderate effect size (d = 0.35) in favor of MemFlex for the cognitive outcome. A small Hazard Ratio (1.08) was observed for time until depressive relapse, along with a negligible effect size for depression-free days (d = 0.11). Although MemFlex produced long-term improvement in memory retrieval skills, there was little support for MemFlex as a relapse prevention program for depression.

Misremembrance of Things Past: Depression Is Associated With Difficulties in the Recollection of Both Specific and Categoric Autobiographical Memories.

Impaired retrieval of specific, autobiographical memories of personally experienced events is characteristic of major depressive disorder (MDD). However, findings in subclinical samples suggest that the reduced specificity phenomenon may reflect a broader impairment in the deliberate retrieval of all autobiographical memory types. This experiment (N = 68) explored this possibility by requiring individuals with and without MDD to complete a cued-recall task that required retrieval of specific, single-incident memories to a block of cues; retrieval of categoric, general memories to a block of cues; and to alternate between retrieval of specific and general memories for a block of cues. Results demonstrated that relative to never-depressed controls, individuals with MDD experience reduced recall of both specific (d = 0.48) and general memories (d = 1.00) along with reduced flexibility in alternating between specific and general memories (d = 0.90). Findings support further development of autobiographical memory-based interventions that target a range of retrieval deficits rather than specificity alone.

A randomised controlled trial of memory flexibility training (MemFlex) to enhance memory flexibility and reduce depressive symptomatology in individuals with major depressive disorder.

Successful navigation within the autobiographical memory store is integral to daily cognition. Impairment in the flexibility of memory retrieval can thereby have a detrimental impact on mental health. This randomised controlled phase II exploratory trial (N = 60) evaluated the potential of a novel intervention drawn from basic science - an autobiographical Memory Flexibility (MemFlex) training programme - which sought to ameliorate memory difficulties and improve symptoms of Major Depressive Disorder. MemFlex was compared to Psychoeducation (an evidence-based low-intensity intervention) to determine the likely range of effects on a primary cognitive target of memory flexibility at post-intervention, and co-primary clinical targets of self-reported depressive symptoms and diagnostic status at three-month follow-up. These effect sizes could subsequently be used to estimate sample size for a fully-powered trial. Results demonstrated small-moderate, though as expected statistically non-significant, effect sizes in favour of MemFlex for memory flexibility (d = 0.34, p = .20), and loss of diagnosis (OR = 0.65, p = .48), along with the secondary outcome of depression-free days (d = 0.36, p = .18). A smaller effect size was observed for between-group difference in self-reported depressive symptoms (d = 0.24, p = .35). Effect sizes in favour of MemFlex in this early-stage trial suggest that fully-powered evaluation of MemFlex may be warranted as an avenue to improving low-intensity treatment of depression. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT02371291.

A cluster randomized controlled platform trial comparing group MEmory specificity training (MEST) to group psychoeducation and supportive counselling (PSC) in the treatment of recurrent depression.

Impaired ability to recall specific autobiographical memories is characteristic of depression, which when reversed, may have therapeutic benefits. This cluster-randomized controlled pilot trial investigated efficacy and aspects of acceptability, and feasibility of MEmory Specificity Training (MEST) relative to Psychoeducation and Supportive Counselling (PSC) for Major Depressive Disorder (N = 62). A key aim of this study was to determine a range of effect size estimates to inform a later phase trial. Assessments were completed at baseline, post-treatment and 3-month follow-up. The cognitive process outcome was memory specificity. The primary clinical outcome was symptoms on the Beck Depression Inventory-II at 3-month follow-up. The MEST group demonstrated greater improvement in memory specificity relative to PSC at post-intervention (d = 0.88) and follow-up (d = 0.74), relative to PSC. Both groups experienced a reduction in depressive symptoms at 3-month follow-up (d = 0.67). However, there was no support for a greater improvement in depressive symptoms at 3 months following MEST relative to PSC (d = -0.04). Although MEST generated changes on memory specificity and improved depressive symptoms, results provide no indication that MEST is superior to PSC in the resolution of self-reported depressive symptoms. Implications for later-phase definitive trials of MEST are discussed.

Study protocol for a randomised, controlled platform trial estimating the effect of autobiographical Memory Flexibility training (MemFlex) on relapse of recurrent major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is a chronic condition. Although current treatment approaches are effective in reducing acute depressive symptoms, rates of relapse are high. Chronic and inflexible retrieval of autobiographical memories, and in particular a bias towards negative and overgeneral memories, is a reliable predictor of relapse. This randomised controlled single-blind trial will determine whether a therapist-guided self-help intervention to ameliorate autobiographical memory biases using Memory Flexibility training (MemFlex) will increase the experience of depression-free days, relative to a psychoeducation control condition, in the 12 months following intervention. METHODS AND ANALYSIS: Individuals (aged 18 and above) with a diagnosis of recurrent MDD will be recruited when remitted from a major depressive episode. Participants will be randomly allocated to complete 4 weeks of a workbook providing either MemFlex training, or psychoeducation on factors that increase risk of relapse. Assessment of diagnostic status, self-report depressive symptoms, depression-free days and cognitive risk factors for depression will be completed post-intervention, and at 6 and 12 months follow-up. The cognitive target of MemFlex will be change in memory flexibility on the Autobiographical Memory Test- Alternating Instructions. The primary clinical endpoints will be the number of depression-free days in the 12 months following workbook completion, and time to depressive relapse. ETHICS AND DISSEMINATION: Ethics approval has been granted by the NHS National Research Ethics Committee (East of England, 11/H0305/1). Results from this study will provide a point-estimate of the effect of MemFlex on depressive relapse, which will be used to inform a fully powered trial evaluating the potential of MemFlex as an effective, low-cost and low-intensity option for reducing relapse of MDD. TRIAL REGISTRATION NUMBER: NCT02614326.