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.

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.

<b><i>Introduction:</i></b> Cognition and emotion are fundamentally integrated in the brain and mutually contribute to behavior. The relation between working memory (WM) and emotion is particularly suited to investigate cognition-emotion interaction since WM is an essential component of many higher cognitive functions. Ketamine affects not only WM but also has a profound impact on emotional processing. Effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Accordingly, a combination of these approaches should be particularly suited to investigate cognition-emotion interaction. <b><i>Methods:</i></b> Seventy five healthy subjects were investigated in a double-blind, placebo-controlled, randomized, single-dose, parallel-group study with three treatment conditions. All subjects underwent two scanning sessions (acute/post 24 h). <b><i>Results:</i></b> Compared to placebo, acute ketamine administration induced significant dissociative, psychotomimetic, and cognitive effects, as well as an increase in neural activity during WM for positive stimuli. Inhibition of glutamate release by pretreatment with lamotrigine did not influence ketamine’s subjective effects, but significantly attenuated its impact on emotional WM and associated neural activity. There was no effect on these measures 24 h after ketamine administration. <b><i>Conclusion:</i></b> Our results demonstrate differential acute effects of modulated glutamate release and a swift restoration of disturbed neurobehavioral homeostasis in healthy subjects.

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.

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 21 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 five key regions associated with the pathophysiology of depression: bilateral dorsolateral prefrontal cortex (l/r DLPFC), pregenual, subgenual, and dorsal anterior cingulate cortex (pgACC, sgACC, dACC). 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 is still facing challenges.

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.

There is intriguing evidence suggesting that ketamine might have distinct acute and delayed neurofunctional effects, as its acute administration transiently induces schizophrenia-like symptoms, while antidepressant effects slowly emerge and are most pronounced 24 h after administration. Studies attempting to characterize ketamine’s mechanism of action by using blood oxygen level dependent (BOLD) imaging have yielded inconsistent results regarding implicated brain regions and direction of effects. This may be due to intrinsic properties of the BOLD contrast, while cerebral blood flow (CBF), as measured with arterial spin labeling, is a single physiological marker more directly related to neural activity. As effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release, a combination of these approaches should be particularly suited to offer novel insights. In total, 75 healthy participants were investigated in a double blind, placebo-controlled, randomized, parallel-group study and underwent two scanning sessions (acute/post 24 h.). Acute ketamine administration was associated with higher perfusion in interior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC), but no other investigated brain region. Inhibition of glutamate release by pretreatment with lamotrigine abolished ketamine’s effect on perfusion. At the delayed time point, pretreatment with lamotrigine was associated with lower perfusion in IFG. These findings underscore the idea that regionally selective patterns of CBF changes reflect proximate effects of modulated glutamate release on neuronal activity. Furthermore, region- specific sustained effects indicate both a swift restoration of disturbed homeostasis in DLPFC as well changes occurring beyond the immediate effects on glutamate signaling in IFG.