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Introduction
Publications
Publications (152)
The importance of differentiating between social concepts when appraising actions (e.g., understanding behavior as critical vs. fault-finding) and its contribution to vulnerability to major depressive disorder (MDD) is unknown. We predicted poor integration of differentiated conceptual knowledge when people with MDD appraise their social actions, c...
Context Proneness to overgeneralization of self-blame is a core part of cognitive vulnerability to major depressive disorder (MDD) and remains dormant after remission of symptoms. Current neuroanatomical models of MDD, however, assume general increases of negative emotions and are unable to explain biases toward emotions entailing self-blame (eg, g...
Background
Many people with depression, for which self-blame plays a key role, are not amenable to current standard psychological treatments. This calls for novel self-guided interventions, which require less attention and motivation. The present study sought to establish proof-of-concept for a novel self-guided intervention in a non-clinical sampl...
Background
Neural predictors underlying variability in depression outcomes are poorly understood. Functional MRI measures of subgenual cortex connectivity, self-blaming and negative perceptual biases have shown prognostic potential in treatment-naïve, medication-free and fully remitting forms of major depressive disorder (MDD). However, their role...
Background
Amygdala and dorsal anterior cingulate cortex responses to facial emotions have shown promise in predicting treatment response in medication-free major depressive disorder (MDD). Here, we examined their role in the pathophysiology of clinical outcomes in more chronic, difficult-to-treat forms of MDD.
Methods
Forty-five people with curre...
Background
A seminal study found higher subgenual frontal cortex resting-state connectivity with 2 left ventral frontal regions and the dorsal midbrain to predict better response to psychotherapy versus medication in individuals with treatment-naïve major depressive disorder (MDD). Here, we examined whether these subgenual networks also play a role...
Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw M...
One’s degree of self-belief or self-worth depends on the beliefs one holds about oneself or one’s self-concept and self-identity.
The neuroanatomical structures relevant for self-beliefs and the conceptual self have been elucidated over the last decades,
but their functional role and whether they are specific for the self or jointly representing in...
Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective const...
The potential impact on mental health of home schooling and social isolation due to COVID-19 lockdowns has led to widespread concern, particularly for adolescents. However, studies including pre-pandemic data from longitudinal cohorts with an assessment of the longer-term impact of the Covid-19 pandemic beyond the first months of 2020 are scarce. T...
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 ho...
Background:
Self-blame-related fMRI measures were shown to predict subsequent recurrence in remitted major depressive disorder (MDD). Their role in current MDD, however, is unknown. We hypothesised that these neural signatures reflect a highly recurrent but remitting course of MDD and therefore predict favourable outcomes over a four-month follow-...
Objectives:
To develop and probe the first computerised decision-support tool to provide antidepressant treatment guidance to general practitioners (GPs) in UK primary care.
Design:
A parallel group, cluster-randomised controlled feasibility trial, where individual participants were blind to treatment allocation.
Setting:
South London NHS GP p...
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 "hidi...
Background
Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status an...
Introduction:
There has been an increase in the prescription of antidepressants (AD) in primary care (PC). However, it is unclear whether this was explained by a rise in diagnoses with an indication for AD. We investigated the changes in frequency and the variables associated with AD prescription in Catalonia, Spain.
Methods:
We retrieved AD pre...
Importance: Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Identifying neuroimaging-based biomarkers might aid in defining the disease-related dimensions that characterize MDD and predict treatment response.
Objective: To investigate the neuroanatomical dimensions that charact...
Objectives
To develop and probe the first computerised decision-support tool to provide antidepressant treatment guidance to GPs in UK primary care.
Design
A parallel group, cluster-randomised controlled feasibility trial, where individual participants were blind to treatment allocation.
Setting
South London NHS GP practices.
Participants
Ten pr...
Importance: Stratification of depression for personalised treatment is urgently needed to improve poor outcomes. Excessive self-blame-related motivations such as self-punishing tendencies have been proposed to play a key role in the onset and maintenance of depression. Their prognostic role, however, remains elusive.
Objective: Use Virtual Reality...
Background
Despite well-established guidelines for managing major depressive disorder, its extensive disability burden persists. This Value of Treatment mission from the European Brain Council aimed to elucidate the nature and extent of “gaps” between best-practice and current-practice care, specifically to: 1. Identify current treatment gaps along...
We present here a unifying framework for affective phenomena: the Human Affectome. By synthesizing a large body of literature, we have converged on definitions that disambiguate the commonly used terms—affect, feeling, emotion, and mood. Based on this definitional foundation, and under the premise that affective states reflect allostatic concerns,...
Background
Despite common dissatisfaction with the syndromic heterogeneity of major depression, investigations into its symptom structure are scarce. Self-worthlessness/inadequacy is a distinctive and consistent symptom of major depression across cultures.
Aims
We investigated whether self-worthlessness is associated with self-blaming attribution-...
Background: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status a...
Darwin stated that humans have a strong and involuntary tendency to perform certain actions when a specific state of mind is induced. Such “action tendencies” are key to understanding the maladaptive impact of self-blame-related feelings in depression. For example, feeling like “hiding” and “creating a distance from oneself” in a text-based task we...
Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and use normative...
Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if condu...
Background
Overgeneralised self-blame and worthlessness are key symptoms of major depressive disorder (MDD) and have previously been associated with self-blame-selective changes in connectivity between right superior anterior temporal lobe (rSATL) and subgenual frontal cortices. Another study showed that remitted MDD patients were able to modulate...
Background
Treatment-resistant depression (TRD) is classically defined according to the number of suboptimal antidepressant responses experienced, but multidimensional assessments of TRD are emerging and may confer some advantages. Patient characteristics have been identified as risk factors for TRD but may also be associated with TRD severity. The...
Biases towards self-blaming emotions, such as self-contempt/disgust, were previously associated with vulnerability to major depressive disorder (MDD). Self-blaming emotions are thought to prompt specific action tendencies (e.g. “feeling like hiding”), which are likely to be more important for psychosocial functioning than the emotions themselves. S...
Background:
In major depressive disorder (MDD), self-blame-related fMRI measures have shown the potential to be used as prognostic markers for recurrence risk. Like most potential fMRI markers, however, their reliability is unclear. Here, we probed the internal reliability of self-blame-related fMRI measures, as well as the impact of different mod...
Background
Understanding and improving outcomes for people with anxiety or depression often requires large sample sizes. To increase participation and reduce costs, such research is typically unable to utilise “gold-standard” methods to ascertain diagnoses, instead relying on remote, self-report measures.
Aims
Assess the comparability of remote di...
Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and use normative...
Humans are intrinsically motivated to bond with others. The ability to experience affiliative emotions (such as affection/tenderness, sexual attraction, and admiration/awe) may incentivize and promote these affiliative bonds. Here, we interrogate the role of the critical reward circuitry, especially the Nucleus Accumbens (NAcc) and the septo-hypoth...
According to the social domains hypothesis, we reduce the information-processing demands of complex social cues by classifying them into a limited number of domains, each with distinct sets of expectations. This requires rapid identification of violations of the boundaries between domains. We hypothesised that these violations are likely to be asso...
Background:
The Patient Health Questionnaire-9 (PHQ-9) is a widely used measure of depression in primary care. It was, however, originally designed as a diagnostic screening tool, and not for measuring change in response to antidepressant treatment. Although the Quick Inventory of Depressive Symptomology (QIDS-SR-16) has been extensively validated...
Social feelings have conceptual and empirical connections with affect and emotion. In this review, we discuss how they relate to cognition, emotion, behavior and well-being. We examne the functional neuroanatomy and neurobiology of social feelings and their role in adaptive social functioning. Existing neuroscience literature is reviewed to identif...
Background:
Overgeneralised self-blaming emotions, such as self-disgust, are core symptoms of major depressive disorder (MDD) and prompt specific actions (i.e. "action tendencies"), which are more functionally relevant than the emotions themselves. We have recently shown, using a novel cognitive task, that when feeling self-blaming emotions, malad...
Background
: Treatment resistant depression (TRD) poses a significant clinical challenge, despite a range of efficacious specialist treatments. Accurately predicting response a priori may help to alleviate the burden of TRD. This study sought to determine whether outcome prediction can be achieved in a specialist inpatient setting.
Methods
: Patie...
Background:
About 30 to 50% of Primary Care (PC) users in Spain suffer mental health problems, mostly mild to moderate anxious and depressive symptoms, which account for 2% of Spain's total Gross domestic product and 50% of the costs associated to all mental disorders. Mobile health tools have demonstrated to cost-effectively reduce anxious and de...
Background: A high proportion of patients with remitted major depressive disorder (MDD) will experience recurring episodes, whilst some develop resilience and remain in recovery. The neural basis of resilience to recurrence is elusive. Abnormal resting-state connectivity of the subgenual cingulate cortex (sgACC) was previously found in cross-sectio...
The syndromic heterogeneity of major depressive disorder (MDD) hinders understanding of the etiology of predisposing vulnerability traits and underscores the importance of identifying neurobiologically valid phenotypes. Distinctive fMRI biomarkers of vulnerability to MDD subtypes are currently lacking. This study investigated whether remitted melan...
Objectives
A combination of negatively biased information processing and a reduced ability to experience positive emotions can persist into remission from major depression (rMDD). Studies have shown that mindfulness-based cognitive therapy (MBCT) can increase self-reported positive emotions in rMDD participants; similar changes using neuropsycholog...
Background- Overgeneralised self-blaming emotions, such as self-disgust, are core symptoms of major depressive disorder (MDD) and prompt specific actions (i.e. "action tendencies"), which are more functionally relevant than the emotions themselves. We have recently shown, using a novel cognitive task, that when feeling self-blaming emotions, malada...
Background: Research to understand the complex aetiology of depressive and anxiety disorders often requires large sample sizes, but this comes at a cost. Large-scale studies are typically unable to utilise "gold standard" phenotyping methods, instead relying on remote, self-report measures to ascertain phenotypes.
Aims: To assess the comparability...
Background
Persisting self-blaming emotional biases were previously associated with vulnerability to major depressive disorder (MDD). More specifically self-contempt/disgust biases distinguished remitted MDD, compared with never-depressed control participants. The contribution of action tendencies to MDD vulnerability and their relationship with bl...
Moral emotions are thought to influence moral behaviour by providing a driving force to do good and to avoid doing bad. In this study we examined moral emotions; specifically, guilt, shame, annoyance and feeling “bad” from two different perspectives in a moral scenario; the agent and the victim whilst manipulating the intentionality of the harm; in...
Background:
Subgenual cingulate cortex (SCC) responses to self-blaming emotion-evoking stimuli were previously found in individuals prone to self-blame with and without a history of major depressive disorder (MDD). This suggested SCC activation reflects self-blaming emotions such as guilt, which are central to models of MDD vulnerability.
Method:...
Mindfulness-Based-Cognitive-Therapy (MBCT) reduces vulnerability for relapse into depression by helping individuals to counter tendencies to engage in maladaptive repetitive patterns of thinking and respond more compassionately to negative self-judgment. However, little is known about the neural correlates underlying these effects. To elucidate the...
Background:
Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression (TRD). 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...
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...
Neurology and the study of moral cognition and behavior have been closely linked since the 19th century. During the past decade, neuroscientists have employed sophisticated behavioral and anatomical and functional neuroimaging methods to study morality both in healthy volunteers and in patients with developmental and acquired impairments of moral b...
People with mental illness can internalize public prejudice and negative emotional reactions to their group, leading to self-contempt. This study examined self-contempt related to having a mental illness as predictor of suicidality among 77 people with mental illness in Southern Germany. Self-contempt, depressive symptoms, hopelessness, and suicida...
Background: Overgeneralised self-blame and worthlessness are key symptoms of major depressive disorder (MDD) and were previously associated with self-blame-selective changes in connectivity between right superior anterior temporal lobe (rSATL) and subgenual frontal areas. In a previous study, remitted MDD patients successfully modulated guilt-selec...
Previously, using fMRI, we demonstrated lower connectivity between right anterior superior temporal (ATL) and anterior subgenual cingulate (SCC) regions while patients with major depressive disorder (MDD) experience guilt. This neural signature was detected despite symptomatic remission which suggested a putative role in vulnerability. This randomi...
Objectives/Aims
FMRI-neurofeedback for major depressive disorder (MDD) is of great interest to clinicians and neuroscientists. Here, the aim was to review the current clinical trials evidence.
Methods
We undertook a systematic literature search of fMRI-neurofeedback trials in MDD, including our unpublished results.
Results
fMRI-neurofeedback was...
The cerebral correlates of altruistic decisions have increasingly attracted the interest of neuroscientists. To date, investigations on the neural underpinnings of altruistic decisions have primarily been conducted in healthy adults undergoing functional neuroimaging as they engaged in decisions to punish third parties. The chief purpose of the pre...
Humans have a strong need to belong to social groups and a natural inclination to benefit ingroup members. Although the psychological mechanisms behind human prosociality have extensively been studied, the specific neural systems bridging group belongingness and altruistic motivation remain to be identified. Here, we used soccer fandom as an ecolog...
Objective
The objective assessment of socially inappropriate behaviour in patients with frontotemporal lobar degeneration (FTLD) is difficult and hampered by its elusive cognitive basis. Neuropsychological tests of social cognition such as complex theory- of-mind tasks are unlikely to be helpful for early differential diagnosis in the future, becau...
Objective
Using fMRI, we have identified lower coupling between anterior temporal (AT) and subgenual cingulate (SC) cortex while patients with major depressive disorder (MDD) experience guilt. This neural signature was detected despite symptom remission which suggests its role in MDD vulnerability. This double-blind, controlled, randomised and pre-...
Background:
There is contradictory evidence regarding negative memory biases in major depressive disorder (MDD) and whether these persist into remission, which would suggest their role as vulnerability traits rather than correlates of mood state. Early life stress (ELS), common in patients with psychiatric disorders, has independently been associa...