Amygdala response to self-critical stimuli and symptom improvement in psychotherapy for depression.

BACKGROUND: Cognitive-behavioural therapy is efficacious in the treatment of major depressive disorder but response rates are still far from satisfactory. AIMS: To better understand brain responses to individualised emotional stimuli and their association with outcome, to enhance treatment. METHOD: Functional magnetic resonance imaging data were collected prior to individual psychotherapy. Differences in brain activity during passive viewing of individualised self-critical material in 23 unmedicated out-patients with depression and 28 healthy controls were assessed. The associations between brain activity, cognitive and emotional change, and outcome were analysed in 21 patients. RESULTS: Patients showed enhanced activity in the amygdala and ventral striatum compared with the control group. Non-response to therapy was associated with enhanced activity in the right amygdala compared with those who responded, and activity in this region was negatively associated with outcome. Emotional but not cognitive changes mediated this association. CONCLUSIONS: Amygdala hyperactivity may lessen symptom improvement in psychotherapy for depression through attenuating emotional skill acquisition.

Valence and agency influence striatal response to feedback in patients with major depressive disorder.

BACKGROUND: Reduced sensitivity to positive feedback is common in patients with major depressive disorder (MDD). However, findings regarding negative feedback are ambiguous, with both exaggerated and blunted responses being reported. The ventral striatum (VS) plays a major role in processing valenced feedback, and previous imaging studies have shown that the locus of controls (self agency v. external agency) over the outcome influences VS response to feedback. We investigated whether attributing the outcome to one's own action or to an external agent influences feedback processing in patients with MDD. We hypothesized that depressed participants would be less sensitive to the feedback attribution reflected by an altered VS response to self-attributed gains and losses. METHODS: Using functional MRI and a motion prediction task, we investigated the neural responses to self-attributed (SA) and externally attributed (EA) monetary gains and losses in unmedicated patients with MDD and healthy controls. RESULTS: We included 21 patients and 25 controls in our study. Consistent with our prediction, healthy controls showed a VS response influenced by feedback valence and attribution, whereas in depressed patients striatal activity was modulated by valence but was insensitive to attribution. This attribution insensitivity led to an altered ventral putamen response for SA - EA losses in patients with MDD compared with healthy controls. LIMITATIONS: Depressed patients with comorbid anxiety disorder were included. CONCLUSION: These results suggest an altered assignment of motivational salience to SA losses in patients with MDD. Altered striatal response to SA negative events may reinforce the belief of not being in control of negative outcomes contributing to a cycle of learned helplessness.

Preliminary Evidence for a Nexus between Rumination, Behavioural Avoidance, Motive Satisfaction and Depression.

UNLABELLED: The present study tested a theoretically derived link between rumination and depressive symptoms through behavioural avoidance and reduced motive satisfaction as a key aspect of positive reinforcement. Rumination, behavioural avoidance, motive satisfaction and levels of depression were assessed via self-report measures in a clinical sample of 160 patients with major depressive disorder. Path analysis-based mediation analysis was used to estimate the direct and indirect effects as proposed by the theoretical model. Operating in serial, behavioural avoidance and motive satisfaction partially mediated the association between rumination and depressive symptoms, irrespective of gender, medication and co-morbid anxiety disorders. This is the first study investigating the associations between behavioural avoidance, rumination and depression in a clinical sample of depressed patients. The findings are in line with an understanding of rumination in depression as also serving an avoidance function. KEY PRACTITIONER MESSAGE: Rumination, avoidance, motive satisfaction and levels of depressive symptoms were examined in a clinical sample of 160 outpatients with major depressive disorder. Path analysis-based mediation analysis revealed that, operating in serial, avoidance and motive satisfaction partially mediated the link between rumination and levels of depressive symptoms. Findings support an understanding of rumination in depression as serving an avoidance function.

Enhancing reappraisal of negative emotional memories with transcranial direct current stimulation.

Reappraisal of negative memories and experiences is central for mental health and well-being. Deficiency of reappraisal lies at the core of many psychiatric disorders and is a key target for treatment. Here we apply transcranial direct current stimulation (tDCS) to enhance reappraisal of negative emotional memories. In a randomised, sham-controlled, 2 × 2 between-subject and double-blinded study, we applied single sessions of anodal and sham tDCS over the right dorsolateral prefrontal cortex (dlPFC) of 101 healthy participants while reappraising a personal negative memory or engaging in a control task. We hypothesised that (i) reappraisal decreases negative valence, arousal and evaluations of the memory and leads to improved decision making, and (ii) tDCS leads to additional changes in these reappraisal outcomes. In line with these hypotheses, participants' personal memories were rated as less negative and less arousing following reappraisal. Anodal tDCS during reappraisal was associated with significant short-term reductions in negative valence compared to sham stimulation. Our results indicate that tDCS may enhance some of the effects of reappraisal. If replicated, our findings suggest potential benefits elicited by tDCS stimulation that may help optimise current treatment approaches for psychiatric disorders.

Anterior cingulate volume predicts response to psychotherapy and functional connectivity with the inferior parietal cortex in major depressive disorder.

In major depressive disorder (MDD), the anterior cingulate cortex (ACC) has been associated with clinical outcome as well as with antidepressant treatment response. Nonetheless, the association between individual differences in ACC structure and function and the response to cognitive behavioral therapy (CBT) is still unexplored. For this aim, twenty-five unmedicated patients with MDD were scanned with structural and resting state functional magnetic resonance imaging before the beginning of CBT treatment. ACC morphometry was correlated with clinical changes following psychotherapy. Furthermore, whole-brain resting state functional connectivity with the ACC was correlated with clinical measures. Greater volume in the left subgenual (subACC), the right pregenual (preACC), and the bilateral supragenual (supACC) predicted depressive symptoms improvement after CBT. Greater subACC volume was related to stronger functional connectivity with the inferior parietal cortex and dorsolateral prefrontal cortex. Stronger subACC-inferior parietal cortex connectivity correlated with greater adaptive rumination. Greater preACC volume was associated with stronger functional connectivity with the inferior parietal cortex and ventrolateral prefrontal cortex. In contrast, greater right supACC volume was related to lower functional connectivity with the inferior parietal cortex. These results suggest that ACC volume and its functional connectivity with the fronto-parietal cortex are associated with CBT response in MDD, and this may be mediated by adaptive forms of rumination. Our findings support the role of the subACC as a potential predictor for CBT response.

Altered dynamics of brain connectivity in major depressive disorder at-rest and during task performance.

Major depressive disorder (MDD) has been associated with alterations in several functional brain networks. Previous studies investigating brain networks in MDD during the performance of a task have yielded inconsistent results with the function of the brain at rest. In this study, we used functional magnetic resonance imaging at rest and during a goal-directed task to investigate dynamics of functional connectivity in 19 unmedicated patients with MDD and 19 healthy controls across both experimental paradigms. Patients had spatial differences in the default mode network (DMN), in the executive network (EN), and in the dorsal attention network (DAN) compared to controls at rest and during task performance. In patients the amplitude of the low frequency (LFO) oscillations was reduced in the motor and in the DAN networks during both paradigms. There was a diagnosis by paradigm interaction on the LFOs amplitude of the salience network, with increased amplitude change between task and rest in patients relative to controls. Our findings suggest that the function of several networks could be intrinsically affected in MDD and this could be viable phenotype for the investigation on the neurobiological mechanisms of this disorder and its treatment.

Prefrontal thinning affects functional connectivity and regional homogeneity of the anterior cingulate cortex in depression.

Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment.

Neural representation and clinically relevant moderators of individualised self-criticism in healthy subjects.

Many people routinely criticise themselves. While self-criticism is largely unproblematic for most individuals, depressed patients exhibit excessive self-critical thinking, which leads to strong negative affects. We used functional magnetic resonance imaging in healthy subjects (N = 20) to investigate neural correlates and possible psychological moderators of self-critical processing. Stimuli consisted of individually selected adjectives of personally negative content and were contrasted with neutral and negative non-self-referential adjectives. We found that confrontation with self-critical material yielded neural activity in regions involved in emotions (anterior insula/hippocampus-amygdala formation) and in anterior and posterior cortical midline structures, which are associated with self-referential and autobiographical memory processing. Furthermore, contrasts revealed an extended network of bilateral frontal brain areas. We suggest that the co-activation of superior and inferior lateral frontal brain regions reflects the recruitment of a frontal top-down pathway, representing cognitive reappraisal strategies for dealing with evoked negative affects. In addition, activation of right superior frontal areas was positively associated with neuroticism and negatively associated with cognitive reappraisal. Although these findings may not be specific to negative stimuli, they support a role for clinically relevant personality traits in successful regulation of emotion during confrontation with self-critical material.

Self-compassion in depression: associations with depressive symptoms, rumination, and avoidance in depressed outpatients.

Self-compassion involves being kind to oneself when challenged with personal weaknesses or hardship and has been claimed to be associated with resilience in various areas. So far, there are only a handful of studies that investigate self-compassion and its relation to clinical depression. Therefore, the principal goals of the present study were (a) to compare self-compassion in clinically depressed patients and never-depressed subjects, (b) to investigate self-compassion and its relation to cognitive-behavioral avoidance and rumination in depressed outpatients, and (c) to investigate rumination and avoidance as mediators of the relationship between self-compassion and depressive symptoms. One hundred and forty-two depressed outpatients and 120 never-depressed individuals from a community sample completed a self-report measure of self-compassion along with other measures. Results indicate that depressed patients showed lower levels of self-compassion than never-depressed individuals, even when controlled for depressive symptoms. In depressed outpatients, self-compassion was negatively related to depressive symptoms, symptom-focused rumination, as well as cognitive and behavioral avoidance. Additionally, symptom-focused rumination and cognitive and behavioral avoidance mediated the relationship between self-compassion and depressive symptoms. These findings extend previous research on self-compassion, its relation to depression, as well as processes mediating this relationship, and highlight the importance of self-compassion in clinically depressed patients. Since depressed patients seem to have difficulties adopting a self-compassionate attitude, psychotherapists are well advised to explore and address how depressed patients treat themselves.