Else Schneider

Background. Anhedonia is a core symptom of depression associated with a poor disease course, high symptom burden, and non-response to standard therapies. As first-line treatments exhibit limited effects on anhedonia, alternative interventions with robust antianhedonic properties are urgently needed. Clinical observations and preliminary studies suggest that electroconvulsive therapy (ECT) might alleviate anhedonic symptoms; however, empirical evidence remains scarce. Aims. To address this research gap, we evaluated the effectiveness of ECT in reducing anhedonia and explored its temporal relationship with general depressive symptoms. Method. Method In a clinical sample of 67 patients with depression undergoing ECT, anhedonia (Snaith–Hamilton Pleasure Scale) and depression severity (Montgomery–Åsberg Depression Rating Scale; Beck Depression Inventory-II) were assessed across four time points: pre-ECT, after the sixth session, post-ECT, and at a 2–3 month follow-up during the maintenance phase. Data were analysed using multilevel models, cross-lagged panel models, and response and remission analyses. Results. Clinically meaningful improvements in anhedonia occurred after the sixth session (d = –0.73, 95% CI [–1.00, –0.46], p < .001), peaked at post-treatment (d = –1.07, 95% CI [–1.36, –0.78], p < .001), and were largely sustained at follow-up (d = –0.84, 95% CI [–1.15, –0.54], p < .001). Exploratory analyses suggested that reductions in anhedonia after the sixth session may preceded and predicted subsequent alleviation of broader depressive symptoms during acute ECT. Conclusions. ECT exerted rapid, clinically meaningful effects on anhedonia. Thus, ECT could be considered earlier in treatment algorithms for patients with pronounced anhedonia and prior resistance to standard therapies, particularly in severe or urgent cases of depression and anhedonia. Future studies using intensive longitudinal designs are needed to clarify whether improvements in anhedonia act as a potential catalyst for broader depressive symptoms in ECT.

SUMMARY: Electroconvulsive therapy (ECT) is a highly effective treatment for several psychiatric disorders, though its biological mechanisms remain unclear. Its therapeutic action has traditionally been attributed to the generalized seizure ECT induces. However, this view is challenged by the recent finding that electroconvulsive stimulation (ECS) can trigger a cortical spreading depression (CSD). Because CSD triggers massive intracellular molecular changes, we hypothesized that it could be a key mediator of ECT’s therapeutic, plasticity-inducing effects. We observed similar neuronal oscillations following ECS in mice and patients undergoing ECT. We show that CSD drives increased expression of the immediate early gene Fos, a key marker of neuronal plasticity, and is associated with factors that predict positive ECT therapeutic outcome. Our results suggest that the therapeutic efficacy of ECT may be mediated by CSD. This challenges the seizure-centric model and implies that CSD, a currently unmonitored neurophysiological event, may serve as a more relevant biomarker for predicting and optimizing therapeutic outcomes of ECT.

We recently indicated that four-week probiotic supplementation significantly reduced depression along with microbial and neural changes in people with depression. Here we further elucidated the biological modes of action underlying the beneficial clinical effects of probiotics by focusing on immune-inflammatory processes. The analysis included a total of N = 43 participants with depression, from which N = 19 received the probiotic supplement and N = 24 received a placebo over four weeks, in addition to treatment as usual. Blood and saliva were collected at baseline, at post-intervention (week 4) and follow-up (week 8) to assess immune-inflammatory markers (IL-1β, IL-6, CRP, MIF), gut-related hormones (ghrelin, leptin), and a stress marker (cortisol). Furthermore, transcriptomic analyses were conducted to identify differentially expressed genes. Finally, we analyzed the associations between probiotic-induced clinical and immune-inflammatory changes. We observed a significant group x time interaction for the gut hormone ghrelin, indicative of an increase in the probiotics group. Additionally, the increase in ghrelin was correlated with the decrease in depressive symptoms in the probiotics group. Transcriptomic analyses identified 51 up- and 57 down-regulated genes, which were involved in functional pathways related to enhanced immune activity. We identified a probiotic-dependent upregulation of the genes ELANE, DEFA4 and OLFM4 associated to immune activation and ghrelin concentration. These results underscore the potential of probiotic supplementation to produce biological meaningful changes in immune activation in patients with depression. Further large-scale mechanistic trials are warranted to validate and extend our understanding of immune-inflammatory measures as potential biomarkers for stratification and treatment response in depression. Trial Registration: www.clinicaltrials.gov, identifier: NCT02957591.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABA_A receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. GABA is readily available and approved as a food supplement in many countries. Although there is substantial evidence indicating that orally ingested GABA may affect GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that oral GABA intake may exert beneficial effects on the brain and psyche through the gut–brain axis. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. Although there is substantial evidence indicating that GABA may be affecting GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that GABA may exert beneficial effects on the brain and psyche through the gut-brain axis. GABA is readily available and approved as a food supplement in many countries. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Episodic memory is the memory for experienced events. A peak competence of episodic memory is the mental combination of experienced events to infer commonalities. This enables adequate interpretation and behavior. Inferring commonalities in episodic memory may proceed with and without consciousness of events. Yet, what distinguishes conscious from unconscious event encoding? This question inspired nine experiments that featured strongly and weakly masked cartoon clips presented for unconscious and conscious encoding and inference. Each clip featured a scene with a visually impenetrable hiding place. Five animals crossed the scene one-by-one consecutively. One animal trajectory represented one event. The animals moved through the hiding place, where they might linger or not. Participants’ task was to observe the animals’ entrances and exits to maintain a mental record of which animals hid simultaneously. We manipulated information load to explore capacity limits of conscious/unconscious encoding. Memory of inferences was tested immediately or 3.5 or 6 minutes following encoding. Participants retrieved inferences well when encoding was conscious. When encoding was unconscious, participants needed to give retrieval responses intuitively. Only habitually intuitive decision-makers exhibited significant delayed retrieval of inferences drawn unconsciously. Hippocampal activity increased with correct retrieval responses and correlated with retrieval success at both consciousness levels. With increasing information load, delayed retrieval performance remained only stable when encoding had been unconscious. A strong hippocampal-neocortical functional connectivity hallmarked conscious memories. A sparse coding hallmarked unconscious memories. Sparse coding may have enlarged memory capacity. Hence, levels of consciousness influenced the memories’ behavioral impact, representational code, and memory capacity.