Subgenual activation and the finger of blame: individual differences and depression vulnerability.

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: Here, we re-examined these hypotheses in an independent larger sample. A total of 109 medication-free participants (70 with remitted MDD and 39 healthy controls) underwent fMRI whilst judging self- and other-blaming emotion-evoking statements. They also completed validated questionnaires of proneness to self-blaming emotions including those related to internal (autonomy) and external (sociotropy) evaluation, which were subjected to factor analysis. RESULTS: An interaction between group (remitted MDD v. Control) and condition (self- v. other-blame) was observed in the right SCC (BA24). This was due to higher SCC signal for self-blame in remitted MDD and higher other-blame-selective activation in Control participants. Across the whole sample, extracted SCC activation cluster averages for self- v. other-blame were predicted by a regression model which included the reliable components derived from our factor analysis of measures of proneness to self-blaming emotions. Interestingly, this prediction was solely driven by autonomy/self-criticism, and adaptive guilt factors, with no effect of sociotropy/dependency. CONCLUSIONS: Despite confirming the prediction of SCC activation in self-blame-prone individuals and those vulnerable to MDD, our results suggest that SCC activation reflects blame irrespective of where it is directed rather than selective for self. We speculate that self-critical individuals have more extended SCC representations for blame in the context of self-agency

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Recruiting for research studies using online public advertisements:examples from research in affective disorders

Successful recruitment is vital for any research study. Difficulties in recruitment are not uncommon and can have important implications. This is particularly relevant to research conducted in affective disorders due to the nature of the conditions and the clinical services that serve these patients. Recently, online public advertisements have become more generally accessible and may provide an effective way to recruit patient populations. However, there is paucity of evidence on their viability as a method of recruiting patients into studies of disease mechanisms in these disorders. Public advertisement methods can be useful when researchers require specific populations, such as those not receiving pharmacological treatment. This work describes our experience in successfully recruiting participants into neuroimaging research studies in affective disorders using online public advertisements. Results suggest that these online public advertisements are an effective method for successfully recruiting participants with affective disorders into research studies, particularly for research focusing on disease mechanisms in specific populations

The role of self-blame and worthlessness in the psychopathology of major depressive disorder

AbstractBackgroundCognitive models predict that vulnerability to major depressive disorder (MDD) is due to a bias to blame oneself for failure in a global way resulting in excessive self-blaming emotions, decreased self-worth, hopelessness and depressed mood. Clinical studies comparing the consistency and coherence of these symptoms in order to probe the predictions of the model are lacking.Methods132 patients with remitted MDD and no relevant lifetime co-morbid axis-I disorders were assessed using a phenomenological psychopathology-based interview (AMDP) including novel items to assess moral emotions (n=94 patients) and the structured clinical interview-I for DSM-IV-TR. Cluster analysis was employed to identify symptom coherence for the most severe episode.ResultsFeelings of inadequacy, depressed mood, and hopelessness emerged as the most closely co-occurring and consistent symptoms (≥90% of patients). Self-blaming emotions occurred in most patients (>80%) with self-disgust/contempt being more frequent than guilt, followed by shame. Anger or disgust towards others was experienced by only 26% of patients. 85% of patients reported feelings of inadequacy and self-blaming emotions as the most bothering symptoms compared with 10% being more distressed by negative emotions towards others.LimitationsSymptom assessment was retrospective, but this is unlikely to have biased patients towards particular emotions relative to others.ConclusionsAs predicted, feelings of inadequacy and hopelessness were part of the core depressive syndrome, closely co-occurring with depressed mood. Self-blaming emotions were highly frequent and bothering but not restricted to guilt. This calls for a refined assessment of self-blaming emotions to improve the diagnosis and stratification of MDD

Self-blame-Selective Hyperconnectivity Between Anterior Temporal and Subgenual Cortices and Prediction of Recurrent Depressive Episodes.

Importance: Patients with remitted major depressive disorder (MDD) were previously found to display abnormal functional magnetic resonance imaging connectivity (fMRI) between the right superior anterior temporal lobe (RSATL) and the subgenual cingulate cortex and adjacent septal region (SCSR) when experiencing self-blaming emotions relative to emotions related to blaming others (eg, "indignation or anger toward others"). This finding provided the first neural signature of biases toward overgeneralized self-blaming emotions (eg, "feeling guilty for everything"), known to have a key role in cognitive vulnerability to MDD. It is unknown whether this neural signature predicts risk of recurrence, a crucial step in establishing its potential as a prognostic biomarker, which is urgently needed for stratification into pathophysiologically more homogeneous subgroups and for novel treatments. Objective: To use fMRI in remitted MDD at baseline to test the hypothesis that RSATL-SCSR connectivity for self-blaming relative to other-blaming emotions predicts subsequent recurrence of depressive episodes. Design, setting, and participants: A prospective cohort study from June 16, 2011, to October 10, 2014, in a clinical research facility completed by 75 psychotropic medication-free patients with remitted MDD and no relevant comorbidity. In total, 31 remained in stable remission, and 25 developed a recurring episode over the 14 months of clinical follow-up and were included in the primary analysis. Thirty-nine control participants with no personal or family history of MDD were recruited for further comparison. Main outcomes and measures: Between-group difference (recurring vs stable MDD) in RSATL connectivity, with an a priori SCSR region of interest for self-blaming vs other-blaming emotions. Results: We corroborated our hypothesis that during the experience of self-blaming vs other-blaming emotions, RSATL-SCSR connectivity predicted risk of subsequent recurrence. The recurring MDD group showed higher connectivity than the stable MDD group (familywise error-corrected P \u3c .05 over the a priori SCSR region of interest) and the control group. In addition, the recurring MDD group also exhibited RSATL hyperconnectivity with the right ventral putamen and claustrum and the temporoparietal junction. Together, these regions predicted recurrence with 75% accuracy. Conclusions and relevance: To our knowledge, this study is the first to provide a robust demonstration of an fMRI signature of recurrence risk in remitted MDD. Additional studies are needed for its further optimization and validation as a prognostic biomarker

BOLD fMRI results.

<p>Only regions are reported that survived voxel- or cluster-based FWE-corrected p = .05 over the whole brain or our <i>a priori</i> ROIs. c = cluster-based FWE-correction. 1 = ROI with strong a priori predictions. 2 = Control ROI with weak a priori predictions. Control group: N = 18, remitted MDD group: N = 21.</p>*<p>Additional analyses for each group separately showed that the amygdala and posterior insula were activated for shame vs. guilt in the MDD group, but not for guilt vs. shame in the control group (at FWE-corrected p = .10 over ROIs).</p