Virtual reality-assessment of social interactions and prognosis in depression.

BACKGROUND: Freud proposed that excessive self-blame-related motivations such as self-punishing tendencies play a key role in depression. Most of the supporting evidence, however, is based on cross-sectional studies and questionnaire measures. METHODS: In this pre-registered (NCT04593537) study, we used a novel Virtual Reality (VR) task to determine whether maladaptive self-blame-related action tendencies prospectively identify a subgroup of depression with poor prognosis when treated as usual over four months in primary care. Ninety-eight patients with depression (Patient Health Questionnaire-9 ≥ 15), screening negatively for bipolar and alcohol/substance use disorders, completed the VR-task at baseline (n = 93 completed follow-up). RESULTS: Our pre-registered statistical/machine learning model prospectively predicted a cross-validated 19 % of variance in depressive symptoms. Contrary to our specific predictions, and in accordance with Freud's observations, feeling like punishing oneself emerged as prognostically relevant rather than feeling like hiding or creating a distance from oneself. Using a principal components analysis of all pre-registered continuous measures, a factor most strongly loading on feeling like punishing oneself for other people's wrongdoings (ß = 0.23, p = 0.01), a baseline symptom factor (ß = 0.30, p = 0.006) and Maudsley Staging Method treatment-resistance scores (ß = 0.28, p = 0.009) at baseline predicted higher depressive symptoms after four months. LIMITATIONS: Patients were not assessed with a diagnostic interview. CONCLUSIONS: Independently and apart from known clinical variables, feeling like punishing oneself emerged as a distinctly relevant prognostic factor and should therefore be assessed and tackled in personalised care pathways for difficult-to-treat depression.

Economic impact of reducing treatment gaps in depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent across Europe. While evidence-based treatments exist, many people with MDD have their condition undetected and/or untreated. This study aimed to assess the cost-effectiveness of reducing treatment gaps using a modeling approach. METHODS: A decision-tree model covering a 27-month time horizon was used. This followed a care pathway where MDD could be detected or not, and where different forms of treatment could be provided. Expected costs pertaining to Germany, Hungary, Italy, Portugal, Sweden, and the UK were calculated and quality-adjusted life years (QALYs) were estimated. The incremental costs per QALY of reducing detection and treatment gaps were estimated. RESULTS: The expected costs with a detection gap of 69% and treatment gap of 50% were €1236 in Germany, €476 in Hungary, €1413 in Italy, €938 in Portugal, €2093 in Sweden, and €1496 in the UK. The incremental costs per QALY of reducing the detection gap to 50% ranged from €2429 in Hungary to €10,686 in Sweden. The figures for reducing the treatment gap to 25% ranged from €3146 in Hungary to €13,843 in Sweden. CONCLUSIONS: Reducing detection and treatment gaps, and maintaining current patterns of care, is likely to increase healthcare costs in the short term. However, outcomes are improved, and reducing these gaps to 50 and 25%, respectively, appears to be a cost-effective use of resources.

Remote virtual reality assessment elucidates self-blame-related action tendencies in depression.

BACKGROUND: Action tendencies are implicit cognitive and motivational states before an action is taken, such as feeling like hiding when experiencing shame or guilt, independent of the actions people decide to take. Such "action tendencies" are key to understanding the maladaptive impact of self-blame in depression. For example, feeling like "hiding" in a text-based task was previously associated with recurrence risk in remitted depression. Despite their functional importance, action tendencies have not been systematically investigated in current depression, which was the aim of this pre-registered study. METHODS: We developed and validated the first virtual reality (VR) assessment of blame-related action tendencies and compared current depression (n = 98) with control participants (n = 40). The immersive VR-task, pre-programmed on devices sent to participants' homes, used hypothetical social interactions, in which either participants (self-agency) or their friend (other-agency) were described to have acted inappropriately. RESULTS: Compared with controls, people with depression showed a maladaptive profile: particularly in the other-agency condition, rather than feeling like verbally attacking their friend, they were prone to feeling like hiding, and punishing themselves. Interestingly, feeling like punishing oneself was associated with a history of self-harm but not suicide attempts. CONCLUSIONS: Current depression and self-harm history were linked with distinctive motivational signatures, paving the way for remote VR-based stratification and treatment.

Immunometabolism pathways as the basis for innovative anti-viral strategies (INITIATE): A Marie Sklodowska-Curie innovative training network.

The past century has witnessed major advances in the control of many infectious diseases, yet outbreaks and epidemics caused by (re-) emerging RNA viruses continue to pose a global threat to human health. As illustrated by the global COVID19 pandemic, high healthcare costs, economic disruption and loss of productivity reinforce the unmet medical need to develop new antiviral strategies to combat not only the current pandemic but also future viral outbreaks. Pivotal for effective anti-viral defense is the innate immune system, a first line host response that senses and responds to virus infection. While molecular details of the innate immune response are well characterized, this research field is now being revolutionized with the recognition that cell metabolism has a major impact on the antiviral and inflammatory responses to virus infections. A detailed understanding of the role of metabolic regulation with respect to antiviral and inflammatory responses, together with knowledge of the strategies used by viruses to exploit immunometabolic pathways, will ultimately change our understanding and treatment of pathogenic viral diseases. INITIATE is a Marie Sklodowska-Curie Actions Innovative Training Network (MSCA-ITN), with the goal to train 15 early stage PhD researchers (ESRs) to become experts in antiviral immunometabolism (https://initiate-itn.eu/). To this end, INITIATE brings together a highly complementary international team of academic and corporate leaders from 7 European countries, with outstanding track records in the historically distinct research fields of virology, immunology and metabolism. The ESRs of INITIATE are trained in these interdisciplinary research fields through individual investigator-driven research projects, specialized scientific training events, workshops on academia-industry interactions, outreach & communication. INITIATE will deliver a new generation of creative and entrepreneurial researchers who will be able to face the inevitable future challenges in combating viral diseases.

Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines.

BACKGROUND: Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made. METHODS: A systematic literature search identified current treatment guidelines for depression published in English. Guidelines were quality assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Data relating to the prescription of pharmacological augmenters were extracted from those developed with sufficient rigor, and the included recommendations compared. RESULTS: Total of 1696 records were identified, 19 guidelines were assessed for quality, and 10 were included. Guidelines differed in their quality, the stage at which augmentation was recommended, the agents included, and the evidence base cited. Lithium and atypical antipsychotics were recommended by all 10, though the specific advice was not consistent. Of the 15 augmenters identified, no others were universally recommended. CONCLUSIONS: This review provides a comprehensive overview of current pharmacological augmentation recommendations for major depression and will support clinicians in selecting appropriate treatment guidance. Although some variation can be accounted for by date of guideline publication, and limited evidence from clinical trials, there is a clear need for greater consistency across guidelines to ensure patients receive consistent evidence-based care.

Study protocol for the antidepressant advisor (ADeSS): a decision support system for antidepressant treatment for depression in UK primary care: a feasibility study.

INTRODUCTION: The Antidepressant Advisor Study is a feasibility trial of a computerised decision-support tool which uses an algorithm to provide antidepressant treatment guidance for general practitioners (GPs) in the UK primary care service. The tool is the first in the UK to implement national guidelines on antidepressant treatment guidance into a computerised decision-support tool. METHODS AND ANALYSIS: The study is a parallel group, cluster-randomised controlled feasibility trial where participants are blind to treatment allocation. GPs were assigned to two treatment arms: (1) treatment-as-usual (TAU) and (2) computerised decision-support tool to assist with antidepressant choices. The study will assess recruitment and lost to follow-up rates, GP satisfaction with the tool and impact on health service use. A meaningful long-term roll-out unit cost will be calculated for the tool, and service use data will be collected at baseline and follow-up to inform a full economic evaluation of a future trial. ETHICS AND DISSEMINATION: The study has received National Health Service ethical approval from the London-Camberwell St Giles Research Ethics Committee (ref: 17/LO/2074). The trial was pre-registered in the Clinical Trials.gov registry. The results of the study will be published in a pre-publication archive within 1 year of completion of the last follow-up assessment. TRIAL REGISTRATION NUMBER: NCT03628027.

The role of self-blaming moral emotions in major depression and their impact on social-economical decision making.

People with major depressive disorder (MDD) are more prone to experiencing moral emotions related to self-blame, such as guilt and shame. DSM-IV-TR recognizes excessive or inappropriate guilt as one of the core symptoms of current MDD, whereas excessive shame is not part of the criteria for MDD. However, previous studies specifically assessing shame suggested its involvement in MDD. In the first part of this review, we will consider literature discussing the role of self-blaming moral emotions in MDD. These self-blaming moral emotions have been purported to influence people when they make social and financial decisions in cognitive studies, particularly those using neuroeconomical paradigms. Such paradigms aim to predict social behavior in activities of daily living, by using important resource tangibles (especially money) in laboratory conditions. Previous literature suggests that guilt promotes altruistic behavior via acting out reparative tendencies, whereas shame reduces altruism by means of increasing social and interpersonal distance. In the second part of this review, we will discuss the potential influence of self-blaming moral emotions on overt behavior in MDD, reviewing clinical and experimental studies in social and financial decision-making, in which guilt, and shame were manipulated. This is not a well-established area in the depression literature, however in this opinion paper we will argue that studies of moral emotions and their impact on behavioral decision-making are of potential importance in the clinical field, by linking specific symptoms of a disorder to a behavioral outcome which may lead to stratification of clinical diagnoses in the future.