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 this neural signature using functional magnetic resonance imaging (fMRI) neurofeedback training, thereby increasing their self-esteem. The feasibility and potential of using this approach in symptomatic MDD were unknown. Method This single-blind pre-registered randomised controlled pilot trial probed a novel self-guided psychological intervention with and without additional rSATL-posterior subgenual cortex (BA25) fMRI neurofeedback, targeting self-blaming emotions in people with insufficiently recovered MDD and early treatment-resistance (n = 43, n = 35 completers). Participants completed three weekly self-guided sessions to rebalance self-blaming biases. Results As predicted, neurofeedback led to a training-induced reduction in rSATL-BA25 connectivity for self-blame v. other-blame. Both interventions were safe and resulted in a 46% reduction on the Beck Depression Inventory-II, our primary outcome, with no group differences. Secondary analyses, however, revealed that patients without DSM-5-defined anxious distress showed a superior response to neurofeedback compared with the psychological intervention, and the opposite pattern in anxious MDD. As predicted, symptom remission was associated with increases in self-esteem and this correlated with the frequency with which participants employed the psychological strategies in daily life. Conclusions These findings suggest that self-blame-rebalance neurofeedback may be superior over a solely psychological intervention in non-anxious MDD, although further confirmatory studies are needed. Simple self-guided strategies tackling self-blame were beneficial, but need to be compared against treatment-as-usual in further trials. https://doi.org/10.1186/ISRCTN10526888

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 for outcome measurement, it is poorly adopted in UK primary care, and, although free for clinicians, has licensing restrictions for healthcare organisation use. Aims We aimed to develop a modified version of the PHQ-9, the Maudsley Modified PHQ-9 (MM-PHQ-9), for tracking symptom changes in primary care. We tested the measure's validity, reliability and factor structure. Method A sample of 121 participants was recruited across three studies, and comprised 78 participants with major depressive disorder and 43 controls. MM-PHQ-9 scores were compared with the QIDS-SR-16 and Clinical Global Impressions improvement scale, for concurrent validity. Internal consistency of the scale was assessed, and principal component analysis was conducted to determine the items’ factor structure. Results The MM-PHQ-9 demonstrated good concurrent validity with the QIDS-SR-16, and excellent internal consistency. Sensitivity to change over a 14-week period was d = 0.41 compared with d = 0.61 on the QIDS-SR-16. Concurrent validity between the paper and mobile app versions of the MM-PHQ-9 was r = 0.67. Conclusions These results indicate that the MM-PHQ-9 is a valid and reliable measure of depressive symptoms in paper and mobile app format, although further validation is required. The measure was sensitive to change, demonstrating suitability for use in routine outcome assessment.

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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-selective rSATL-subgenual cingulate connectivity using real-time functional magnetic resonance imaging (rtfMRI) neurofeedback training, thereby increasing their self-esteem. The feasibility and potential of using this approach in symptomatic MDD were unknown. Methods: This single-blind pre-registered randomised controlled pilot trial tested the clinical potential of a novel self-guided psychological intervention with and without additional rSATL-posterior subgenual cortex (SC) rtfMRI neurofeedback, targeting self-blaming emotions in insufficiently recovered people with MDD and early treatment-resistance (n=43, n=35 completers). Following a diagnostic baseline assessment, patients completed three self-guided sessions to rebalance self-blaming biases and a post-treatment assessment. The fMRI neurofeedback software FRIEND was used to measure rSATL-posterior SC connectivity, while the BDI-II was administered to assess depressive symptom severity as a primary outcome measure. Results: Both interventions were demonstrated to be safe and beneficial, resulting in a mean reduction of MDD symptom severity by 46% and response rates of more than 55%, with no group difference. Secondary analyses, however, revealed a differential response on our primary outcome measure between MDD patients with and without DSM-5 defined anxious distress. Stratifying by anxious distress features was investigated, because this was found to be the most common subtype in our sample. MDD patients without anxious distress showed a higher response to rtfMRI neurofeedback training compared to the psychological intervention, with the opposite pattern found in anxious MDD. We explored potentially confounding clinical differences between subgroups and found that anxious MDD patients were much more likely to experience anger towards others as measured on our psychopathological interview which might play a role in their poorer response to neurofeedback. In keeping with the hypothesis that self-worth plays a key role in MDD, improvement on our primary outcome measure was correlated with increases in self-esteem after the intervention and this correlated with the frequency with which participants employed the strategies to tackle self-blame outside of the treatment sessions. Conclusions: These findings suggest that self-blame-selective rtfMRI neurofeedback training may be superior over a solely psychological intervention in non-anxious MDD, although further confirmatory studies are needed. The self-guided psychological intervention showed a surprisingly high clinical potential in the anxious MDD group which needs further confirmation compared vs treatment-as-usual. Future studies need to investigate whether self-blame-selective rSATL-SC connectivity changes are irrelevant in anxious MDD, which could explain their response being better to the psychological intervention without interfering neurofeedback.

BackgroundOvergeneralised 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, maladaptive action tendencies (feeling like “hiding” and like “creating a distance from oneself”) and an overgeneralised perception of control are characteristic of MDD, even after remission of symptoms. Here, we probed the potential of this cognitive signature, and its combination with previously employed fMRI measures, to predict individual recurrence risk. For this purpose, we developed a user-friendly hybrid machine-/statistical-learning tool which we make freely available.Methods52 medication-free remitted MDD patients, who had completed the Action Tendencies Task and our self-blame fMRI task at baseline, were followed up clinically over 14-months to determine recurrence. Prospective prediction models included baseline maladaptive self-blame-related action tendencies and anterior temporal fMRI connectivity patterns across a set of fronto-limbic a priori regions of interest, as well as established clinical and standard psychological predictors. Prediction models used elastic-net regularised logistic regression with nested 10-fold cross-validation.ResultsCross-validated discrimination was highly promising (AuC≥0.86), and positive predictive values over 80% were achieved when including fMRI in multi-modal models, but only up to 71% (AuC≤.74) when solely relying on cognitive and clinical measures.ConclusionsThis shows the high potential of multi-modal signatures of self-blaming biases to predict recurrence risk at an individual level, and calls for external validation in an independent sample.