Aberrant associations between neuronal resting-state fluctuations and working memory-induced activity in major depressive disorder.

Previous investigations have revealed performance deficits and altered neural processes during working-memory (WM) tasks in major depressive disorder (MDD). While most of these studies used task-based functional magnetic resonance imaging (fMRI), there is an increasing interest in resting-state fMRI to characterize aberrant network dynamics involved in this and other MDD-associated symptoms. It has been proposed that activity during the resting-state represents characteristics of brain-wide functional organization, which could be highly relevant for the efficient execution of cognitive tasks. However, the dynamics linking resting-state properties and task-evoked activity remain poorly understood. Therefore, the present study investigated the association between spontaneous activity as indicated by the amplitude of low frequency fluctuations (ALFF) at rest and activity during an emotional n-back task. 60 patients diagnosed with an acute MDD episode, and 52 healthy controls underwent the fMRI scanning procedure. Within both groups, positive correlations between spontaneous activity at rest and task-activation were found in core regions of the central-executive network (CEN), whereas spontaneous activity correlated negatively with task-deactivation in regions of the default mode network (DMN). Compared to healthy controls, patients showed a decreased rest-task correlation in the left prefrontal cortex (CEN) and an increased negative correlation in the precuneus/posterior cingulate cortex (DMN). Interestingly, no significant group-differences within those regions were found solely at rest or during the task. The results underpin the potential value and importance of resting-state markers for the understanding of dysfunctional network dynamics and neural substrates of cognitive processing.

Investigating the impact of rumination and adverse childhood experiences on resting-state neural activity and connectivity in depression.

BACKGROUND: Both ruminative thought processes and adverse childhood experiences (ACEs) are well-established risk factors for the emergence and maintenance of depression. However, the neurobiological mechanisms underlying these associations remain poorly understood. METHODS: We examined resting-state functional magnetic resonance imaging data (3 T Tim Trio MR scanner; Siemens, Erlangen) of 44 individuals diagnosed with an acute depressive episode. Specifically, we focused on investigating functional brain activity and connectivity within and between three large-scale neural networks associated with processes affected in depression: the default mode network (DMN), the salience network (SN), and the central executive network (CEN). Correlational and regression-based analyses were performed. RESULTS: Our regions of interest analyses revealed that region-specific spontaneous neural activity in the anterior DMN was associated with self-reported trait rumination, specifically, the pregenual anterior cingulate cortex (pgACC). Furthermore, using a liberal statistical threshold, we found that spontaneous neural activity of the ventromedial prefrontal cortex and the pgACC were associated with depression symptom severity. Neither spontaneous neural activity in the SN and CEN nor functional connectivity within and across the investigated networks was associated with depression severity or rumination. Furthermore, there was no association between ACEs and brain activity and connectivity. LIMITATIONS: Lack of a formal control group or low-risk group for comparison. CONCLUSIONS: Overall, our results indicate network-specific changes in spontaneous brain activity, that are linked to both depression severity and rumination. Findings underscore the crucial role of the pgACC in depression and contribute to a dimensional and symptom-based understanding of depression-related network imbalances.

The influence of childhood emotional maltreatment on cognitive symptoms, rumination, and hopelessness in adulthood depression.

Childhood emotional maltreatment (CEM) is a risk factor for the pathogenesis of depressive disorders. However, it is not clear whether CEM is more strongly related to specific symptoms of depression and whether specific traits or cognitive states may mediate the association between CEM and depressive symptoms. In our cross-sectional study, including 72 patients with a current depressive episode, we investigated if CEM is specifically related to cognitive symptoms of depression. In addition, we evaluated whether CEM also influences the extent of rumination and hopelessness in adult depression. Using multiple regression analyses, we tested if CEM and rumination could predict cognitive symptoms and hopelessness. A structural equation model (SEM) was used to examine if rumination mediates the relationship between CEM and cognitive symptoms. Correlational analyses revealed that CEM was related to cognitive symptoms, rumination, and hopelessness. The regression analyses showed that only rumination was a significant predictor for cognitive symptoms and hopelessness, whereas CEM could not significantly predict the two constructs. SEM revealed that the association between CEM and cognitive symptoms in adult depression was mediated by rumination. Our results thereby suggest that CEM is a risk factor particularly for the development of cognitive symptoms as well as rumination and hopelessness in adult depression. However, the influence on cognitive symptomatology seems to be indirectly regulated by rumination. These findings may contribute to a better understanding of processes that promote depression, as well as provide guidance for more targeted treatment options.

Ten simple rules for implementing open and reproducible research practices after attending a training course.

Open, reproducible, and replicable research practices are a fundamental part of science. Training is often organized on a grassroots level, offered by early career researchers, for early career researchers. Buffet style courses that cover many topics can inspire participants to try new things; however, they can also be overwhelming. Participants who want to implement new practices may not know where to start once they return to their research team. We describe ten simple rules to guide participants of relevant training courses in implementing robust research practices in their own projects, once they return to their research group. This includes (1) prioritizing and planning which practices to implement, which involves obtaining support and convincing others involved in the research project of the added value of implementing new practices; (2) managing problems that arise during implementation; and (3) making reproducible research and open science practices an integral part of a future research career. We also outline strategies that course organizers can use to prepare participants for implementation and support them during this process.

Functional connectivity changes between amygdala and prefrontal cortex after ECT are associated with improvement in distinct depressive symptoms.

Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression. However, the underlying mechanisms of action are not yet fully understood. The investigation of depression-specific networks using resting-state fMRI and the relation to differential symptom improvement might be an innovative approach providing new insights into the underlying processes. In this naturalistic study, we investigated the relationship between changes in resting-state functional connectivity (rsFC) and symptom improvement after ECT in 21 patients with treatment-resistant depression. We investigated rsFC before and after ECT and focused our analyses on FC changes directly related to symptom reduction and on FC at baseline to identify neural targets that might predict individual clinical responses to ECT. Additional analyses were performed to identify the direct relationship between rsFC change and symptom dimensions such as sadness, negative thoughts, detachment, and neurovegetative symptoms. An increase in rsFC between the left amygdala and left dorsolateral prefrontal cortex (DLPFC) after ECT was related to overall symptom reduction (Bonferroni-corrected p = 0.033) as well as to a reduction in specific symptoms such as sadness (r = 0.524, uncorrected p = 0.014), negative thoughts (r = 0.700, Bonferroni-corrected p = 0.002) and detachment (r = 0.663, p = 0.004), but not in neurovegetative symptoms. Furthermore, high baseline rsFC between the left amygdala and the right frontal pole (FP) predicted treatment outcome (uncorrected p = 0.039). We conclude that changes in FC in regions of the limbic-prefrontal network are associated with symptom improvement, particularly in affective and cognitive dimensions. Frontal-limbic connectivity has the potential to predict symptom improvement after ECT. Further research combining functional imaging biomarkers and a symptom-based approach might be promising.

Investigation of Neurofunctional Changes Over the Course of Electroconvulsive Therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for patients suffering from depression. Yet the exact neurobiological mechanisms underlying the efficacy of ECT and indicators of who might respond best to it remain to be elucidated. Identifying neural markers that can inform about an individual's response to ECT would enable more optimal treatment strategies and increase clinical efficacy. METHODS: Twenty-one acutely depressed inpatients completed an emotional working memory task during functional magnetic resonance imaging before and after receiving treatment with ECT. Neural activity was assessed in 5 key regions associated with the pathophysiology of depression: bilateral dorsolateral prefrontal cortex and pregenual, subgenual, and dorsal anterior cingulate cortex. Associations between brain activation and clinical improvement, as reflected by Montgomery-Åsberg Depression Rating Scale scores, were computed using linear regression models, t tests, and Pearson correlational analyses. RESULTS: Significant neurobiological prognostic markers or changes in neural activity from pre- to post ECT did not emerge. CONCLUSIONS: We could not confirm normalization effects and did not find significant neural markers related to treatment response. These results demonstrate that the search for reliable and clinically useful biomarkers for ECT treatment remains in its initial stages and still faces challenges.

EffECTively Treating Depression: A Pilot Study Examining Manualized Group CBT as Follow-Up Treatment After ECT.

Background: There is an urgent need for effective follow-up treatments after acute electroconvulsive therapy (ECT) in depressed patients. Preliminary evidence suggests psychotherapeutic interventions to be a feasible and efficacious follow-up treatment. However, there is a need for research on the long-term usefulness of such psychotherapeutic offers in a naturalistic setting that is more representative of routine clinical practice. Therefore, the aim of the current pilot study was to investigate the effects of a half-open continuous group cognitive behavioral therapy (CBT) with cognitive behavioral analysis system of psychotherapy elements as a follow-up treatment for all ECT patients, regardless of response status after ECT, on reducing depressive symptoms and promoting psychosocial functioning. Method: Group CBT was designed to support patients during the often-difficult transition from inpatient to outpatient treatment. In a non-controlled pilot trial, patients were offered 15weekly sessions of manualized group CBT (called EffECTiv 2.0). The Montgomery-Åsberg Depression Rating Scale was assessed as primary outcome; the Beck Depression Inventory, WHO Quality of Life Questionnaire-BREF, and the Cognitive Emotion Regulation Questionnaire were assessed as secondary outcomes. Measurements took place before individual group start, after individual group end, and 6months after individual group end. Results: During group CBT, Post-ECT symptom reduction was not only maintained but there was a tendency toward a further decrease in depression severity. This reduction could be sustained 6months after end of the group, regardless of response status after ECT treatment. Aspects of quality of life and emotion regulation strategies improved during group CBT, and these improvements were maintained 6months after the end of the group. Conclusion: Even though the interpretability of the results is limited by the small sample and the non-controlled design, they indicate that manualized group CBT with cognitive behavioral analysis system of psychotherapy elements might pose a recommendable follow-up treatment option after acute ECT for depressed patients, regardless of response status after ECT. This approach might not only help to further reduce depressive symptoms and prevent relapse, but also promote long-term psychosocial functioning by improving emotion regulation strategies and psychological quality of life and thus could be considered as a valuable addition to clinical routine after future validation.

A symptom-based approach in predicting ECT outcome in depressed patients employing MADRS single items.

Establishing symptom-based predictors of electroconvulsive therapy (ECT) outcome seems promising, however, findings concerning the predictive value of distinct depressive symptoms or subtypes are limited; previous factor-analytic approaches based on the Montgomery-Åsberg Depression Rating Scale (MADRS) remained inconclusive, as proposed factors varied across samples. In this naturalistic study, we refrained from these previous factor-analytic approaches and examined the predictive value of MADRS single items and their change during the course of ECT concerning ECT outcome. We used logistic and linear regression models to analyze MADRS data routinely assessed at three time points in 96 depressed psychiatric inpatients over the course of ECT. Mean age was 53 years (SD 14.79), gender ratio was 58:38 (F:M), baseline MADRS score was M = 30.20 (SD 5.42). MADRS single items were strong predictors of ECT response, remission and overall symptom reduction, especially items 1 (apparent sadness), 2 (reported sadness) and 8 (inability to feel), assessing affective symptoms. Strongest effects were found for regression models including item 2 (reported sadness) with up to 80% correct prediction of ECT outcome. ROC analyses were performed to estimate the optimal cut-point for treatment response. MADRS single items during the course of ECT might pose simple, reliable, time- and cost-effective predictors of ECT outcome. More severe affective symptoms of depression at baseline and a stronger reduction of these affective symptoms during the course of ECT seem to be positively associated with ECT outcome. Precise cut-off values for clinical use were proposed. Generally, these findings underline the benefits of a symptom-based approach in depression research and treatment in addition to depression sum-scores and generalized diagnoses.

Comparison of Four fMRI Paradigms Probing Emotion Processing.

Previous fMRI research has applied a variety of tasks to examine brain activity underlying emotion processing. While task characteristics are known to have a substantial influence on the elicited activations, direct comparisons of tasks that could guide study planning are scarce. We aimed to provide a comparison of four common emotion processing tasks based on the same analysis pipeline to suggest tasks best suited for the study of certain target brain regions. We studied an n-back task using emotional words (EMOBACK) as well as passive viewing tasks of emotional faces (FACES) and emotional scenes (OASIS and IAPS). We compared the activation patterns elicited by these tasks in four regions of interest (the amygdala, anterior insula, dorsolateral prefrontal cortex (dlPFC) and pregenual anterior cingulate cortex (pgACC)) in three samples of healthy adults (N = 45). The EMOBACK task elicited activation in the right dlPFC and bilateral anterior insula and deactivation in the pgACC while the FACES task recruited the bilateral amygdala. The IAPS and OASIS tasks showed similar activation patterns recruiting the bilateral amygdala and anterior insula. We conclude that these tasks can be used to study different regions involved in emotion processing and that the information provided is valuable for future research and the development of fMRI biomarkers.

The role of emotion regulation as a mediator between early life stress and posttraumatic stress disorder, depression and anxiety in Syrian refugees.

Early life stress is an important factor in later psychopathology, including symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety. The purpose of the present study was to investigate the effect of early life stress on psychiatric symptoms within a sample of Syrian refugees. In this model, the use of cognitive emotion regulation strategies was assessed as a potential mediator of the relationship between early life stress and current symptoms of PTSD, depression, and anxiety. Bootstrap analyses were generated to test the indirect effect of emotion regulation (Cognitive Emotion Regulation Questionnaire) on the relationship between early life stress (Childhood Trauma Questionnaire), PTSD (Harvard Trauma Questionnaire), depressive (PHQ-9) and anxiety (GAD-7) symptoms in eighty-nine Syrian refugees resided in Germany (n = 49) and Jordan (n = 40). The indirect effect of maladaptive strategies was significant between early life stress and psychopathology, whereas the mediation effect of adaptive strategies was not significant. The findings provide an evidence that emotional dysregulation is an underlying factor affecting psychological symptoms in refugees with adverse childhood experiences. These results suggest targeting cognitive emotion regulation in prospective prevention and treatment strategies.

Interaction of HPA axis genetics and early life stress shapes emotion recognition in healthy adults.

BACKGROUND: Early life stress (ELS) affects facial emotion recognition (FER), as well as the underlying brain network. However, there is considerable inter-individual variability in these ELS-caused alterations. As the hypothalamic-pituitary-adrenal (HPA) axis is assumed to mediate neural and behavioural sequelae of ELS, the genetic disposition towards HPA axis reactivity might explain differential vulnerabilities. METHODS: An additive genetic profile score (GPS) of HPA axis reactivity was built from 6 SNPs in 3 HPA axis-related genes (FKBP5, CRHR1, NR3C1). We studied two independent samples. As a proof of concept, GPS was tested as a predictor of cortisol increase to a psychosocial challenge (MIST) in a healthy community sample of n = 40. For the main study, a sample of n = 170 completed a video-based FER task and retrospectively reported ELS experiences in the Childhood Trauma Questionnaire (CTQ). RESULTS: GPS positively predicted cortisol increase in the stress challenge over and above covariates. CTQ and genetic profile scores interacted to predict facial emotion recognition, such that ELS had a detrimental effect on emotion processing only in individuals with higher GPS. Post-hoc moderation analyses revealed that, while a less stress-responsive genetic profile was protective against ELS effects, individuals carrying a moderate to high GPS were affected by ELS in their ability to infer emotion from facial expressions. DISCUSSION: These results suggest that a biologically informed genetic profile score can capture the genetic disposition to HPA axis reactivity and moderates the influence of early environmental factors on facial emotion recognition. Further research should investigate the neural mechanisms underlying this moderation. The GPS used here might prove a powerful tool for studying inter-individual differences in vulnerability to early life stress.