Can CBT-E be delivered in an online group format? A pilot study of the Body Image module in a child and adolescent eating disorder service.

The increased prevalence of eating disorders during the COVID-19 pandemic has led to long waiting lists in child and adolescent services. A pilot study was conducted to evaluate the feasibility and acceptability of providing the Body Image module, from the enhanced cognitive behavioral therapy for eating disorders (CBT-E), in a virtual group setting. Primary outcomes were acceptance rates, completion rates, qualitative feedback and quantitative data from routine questionnaires. From 22 eligible referrals, 12 participants accepted and enrolled in therapy. Eight completed all six sessions. Qualitative feedback was positive, with both the content and group nature of the intervention being described as helpful. There was an reduction in scores in the Clinical Impairment Assessment and all subscales of the Eating Disorder Examination for Adolescents, suggesting this was a feasible method of providing psychological therapy within the service. A larger trial is recommended to robustly test the effectiveness of the intervention compared to one-to-one in-person CBT-E, and whether the full CBT-E protocol can be effectively delivered in the same format.

Affective working memory in depression.

Depressed individuals show a wide range of difficulties in executive functioning (including working memory), which can be a significant burden on everyday mental processes. Theoretical models of depression have proposed these difficulties to be especially pronounced in affective contexts. However, evidence investigating affective working memory (WM) capacity in depressed individuals has shown mixed results. The preregistered study used a complex span task, which has been shown to be sensitive to difficulties with WM capacity in affective relative to neutral contexts in other clinical groups, to explore affective WM capacity in clinical depression. Affective WM capacity was compared between individuals with current depression (n = 24), individuals in remission from depression (n = 25), and healthy controls (n = 30). The results showed that, overall, WM capacity was more impaired in the context of negative distractor images, relative to neutral images. Furthermore, those with a lifetime history of depression (individuals with current depression and individuals remitted from depression), performed worse on the task, compared to healthy controls. However, there was no support for the greater disruption of WM capacity in affective compared to neutral contexts in those with a lifetime history of depression. These findings' implications for current models of depression are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Affective Control Training (AffeCT) reduces negative affect in depressed individuals.

Depression is the leading cause of disability worldwide, with prevalence rates rising. Despite the scale of the problem, available pharmacological and psychological interventions only have limited efficacy. The National Institute of Health's Science of Behaviour Change framework proposes to address this issue by capitalising on insights from basic science to identify mechanisms that can be targeted by novel interventions. The current study evaluated the potential of a computerized programme aimed at improving affective control, a mechanistic target involved in both risk and maintenance of depression. In a first phase the cognitive profiles of 48 depressed individuals (mean age: 39 years, 75 % female) were compared to cognitive functioning in 16 never-depressed individuals (mean age: 31 years, 56 % female). The sole index of functioning that differed between diagnostic groups was reaction time across negative and positively valanced trials on an affective Stroop task (d = 0.58). This index was then used to evaluate an affective control training (AffeCT) against a placebo training. Results showed no significant changes on tasks that showed no differences with never-depressed individuals in Phase I. However, compared to placebo training, AffeCT led to significantly greater improvement in the target index, affective Stroop performance (d = 1.17). Importantly, AffeCT led to greater reductions in negative affect as measured by the Positive Affect and Negative Affect Schedule compared to the placebo training (d = 0.98). This proof-of-concept study shows promising benefits of AffeCT on depressed individuals' affect, but not depressive symptoms. It further supports the utility of the Science of Behaviour Change framework, highlighting the need for determining meaningful assays of target mechanisms when evaluating novel interventions.

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.

Risk of Atypical HUS Among Family Members of Patients Carrying Complement Regulatory Gene Abnormality.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is mainly due to complement regulatory gene abnormalities with a dominant pattern but incomplete penetrance. Thus, healthy carriers can be identified in any family of aHUS patients, but it is unpredictable if they will eventually develop aHUS. METHODS: Patients are screened for 10 complement regulatory gene abnormalities and once a genetic alteration is identified, the search is extended to at-risk family members. The present cohort study includes 257 subjects from 71 families: 99 aHUS patients (71 index cases + 28 affected family members) and 158 healthy relatives with a documented complement gene abnormality. RESULTS: Fourteen families (19.7%) experienced multiple cases. Over a cumulative observation period of 7595 person-years, only 28 family members carrying gene mutations experienced aHUS (overall penetrance of 20%), leading to a disease rate of 3.69 events for 1000 person-years. The disease rate was 7.47 per 1000 person-years among siblings, 6.29 among offspring, 2.01 among parents, 1.84 among carriers of variants of uncertain significance, and 4.43 among carriers of causative variants. CONCLUSIONS: The penetrance of aHUS seems a lot lower than previously reported. Moreover, the disease risk is higher in carriers of causative variants and is not equally distributed among generations: siblings and the offspring of patients have a much greater disease risk than parents. However, risk calculation may depend on variant classification that could change over time.

Kidney transplant in patients with atypical hemolytic uremic syndrome in the anti-C5 era: single-center experience with tailored Eculizumab.

RATIONALE AND OBJECTIVE: Patients with atypical hemolytic uremic syndrome (aHUS) have long been considered ineligible for kidney transplantation (KTx) in several centers due to the high risk of disease recurrence, graft loss and life-threatening complications. The availability of Eculizumab (ECU) has now overcome this problem. However, the best approach towards timing, maintenance schedule, the possibility of discontinuation and patient monitoring has not yet been clearly established. STUDY DESIGN: This is a single center case series presenting our experience with KTx in aHUS. SETTING AND PARTICIPANTS: This study included 26 patients (16 females) with a diagnosis of aHUS, who spent a median of 5.5 years on kidney replacement therapy before undergoing KTx. We compared the aHUS relapse rate in three groups of patients who underwent KTx: patients who received no prophylaxis, patients who underwent plasma exchange, those who received Eculizumab prophylaxis. Complement factor H-related disease was by far the most frequent etiology (n = 19 patients). RESULTS: Untreated patients and patients undergoing pre-KTx plasma exchange prophylaxis had a relapse rate of 0.81 (CI 0.30-1.76) and 3.1 (CI 0.64-9.16) events per 10 years cumulative observation, respectively, as opposed to 0 events among patients receiving Eculizumab prophylaxis. The time between Eculizumab doses was tailored based on classic complement pathway activity (target to < 30%). Using this strategy, 12 patients are currently receiving  Eculizumab every 28 days, 5 every 24-25 days, and 3 every 21 days. CONCLUSION: Our experience supports the prophylactic use of Eculizumab in patients with a previous history of aHUS undergoing KTx, especially when complement dysregulation is well documented by molecular biology.

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.

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.

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.