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.

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.

A nomological network for misophonia in two German samples using the S-Five model for misophonia.

The Selective Sound Sensitivity Syndrome Scale (S-Five) is a contemporary and multidimensional self-report instrument measuring different aspects of misophonia. The five-factor scale consists of 25 items measuring the severity of the misophonic experience. The items capture misophonia in relation to internalising and externalising appraisals, perceived threat, aggressive behavior (outbursts), and adverse impact on individuals' lives. It is complemented by a trigger checklist (S-Five-T), measuring the emotional nature and intensity of reactions to sensory triggers. In this work, we administered the S-Five in two German samples with a majority of individuals with significant misophonia. The S-Five and the supplementary S-Five-T were both translated into German using a rigorous translation procedure (i.e., TRAPD) and were separately tested in large German community samples. Psychometric analyses included the evaluation of the factor structure, measurement invariance with respect to age and gender, reliability (internal consistency and stability over time), and an extensive examination of the construct validity in a proposed nomological network. The nomological network we explore in this work consists of several constructs including different misophonic manifestations, anger and aggression, disgust propensity, anxiety sensitivity, depression, obsessive-compulsive traits, and functional impairment in different life domains. Results indicate evidence in line with the nomological network as demonstrated by strong correlations between the S-Five dimensions and convergent measures. All S-Five dimensions strongly correlated with overall misophonic symptoms (r ≥ 0.53). Internalising appraisals were highly associated with insight into excessive or disproportionate reactions to sounds (r ≥ 0.59), externalising appraisals with anger and irritability (r ≥ 0.46), threat with trait anxiety and dysregulation facets (r ≥ 0.62), aggressive behavior (outbursts) with anger and behavioral dysregulation (r ≥ 0.70), and impact with distress and functional impairment (r ≥ 0.64). The results demonstrate that the S-Five has a robust five-factor structure and allows to draw reliable and valid conclusions about misophonic experiences in German samples. The proposed nomological network gives an initial insight into the nature of misophonia and provides a formalized fundament to develop and test further hypotheses about misophonia in a more sophisticated and symptom-oriented way.

Posttraumatic stress in adult civilians exposed to violent conflict, war and associated human rights abuses in the Eastern Mediterranean Region: A systematic review and meta-analysis.

BACKGROUND: The Eastern Mediterranean Region (EMR) is the stage of the world's most violent conflicts and the origin of the largest refugee population worldwide. These conflicts can result in symptoms of posttraumatic stress (PTS). To date, no comprehensive meta-analysis on proportions of PTS in civilians from the EMR has been conducted. Sample characteristics, methodological, conflict-related and displacement-related factors might affect rates of PTS. METHODS: A systematic literature search for studies investigating PTS in adult civilians from the EMR was conducted until March 2020 and resulted in 118 individual study samples that were suitable for inclusion. A quality assessment was conducted. A random effects meta-analysis on proportions and sensitivity analyses were performed, and a 95% prediction interval was calculated. Subgroup analyses to identify moderators (e.g. diagnostic instruments, displacement) were conducted. RESULTS: The quality of the included study samples varied. The pooled estimate of proportions from all 118 study samples was 0.31 (95% CI: 0.27 - 0.35). Heterogeneity was considerable (Q = 10151.58, p < .0001; I2 = 98.64%). The prediction interval was 0.01 to 0.76. The results remained unchanged after excluding nine outlier study samples. Heterogeneity remained high in all subgroups (range of I2: 87.91 to 99.62). LIMITATIONS: Due to heterogeneity the pooled estimate cannot be interpreted. Moderators contributing to heterogeneity could not be detected. CONCLUSIONS: The proportion of symptoms of PTS in civilians from the EMR varies considerably. The prediction interval indicates that the true rate falls between 1% and 76%. Future studies need to identify variables that affect heterogeneity.

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.