Die Elektrokonvulsionstherapie (EKT) ist ein nichtpharmakologisches biologisches Behandlungsverfahren, dessen ausgezeichnete Wirksamkeit v. a. bei depressiven Störungsbildern, aber auch bei Erkrankungen aus dem schizophrenen Formenkreis in einer Vielzahl an kontrollierten Untersuchungen gut belegt werden konnte. Dies gilt sowohl für Akutbehandlungen als auch für eine Erhaltungstherapie zur Rezidivprophylaxe. Sicherheit und Verträglichkeit der EKT sind durch umfangreiche Modifikationen der Stimulationstechnik sowie durch die umfassenden Fortschritte der Anästhesiologie stetig verbessert worden. Somit konnten v. a. in den letzten Jahren viele Kontraindikationen weitgehend relativiert werden, sodass heute auch Patienten mit erhöhten somatischen Risiken eine sichere Behandlung angeboten werden kann. Im vorliegenden Kapitel werden die historische Entwicklung der EKT, Untersuchungen zu Wirkmechanismen, die Indikationsstellung, Kontraindikationen und Risiken sowie die klinische Durchführung der Behandlung im Rahmen der Akutbehandlung sowie der Rezidivprophylaxe dargestellt. Die EKT ist demnach weiterhin eine wichtige Therapieoption, die v. a. schwer erkrankten Patienten, die durch andere Behandlungsformen wie z. B. eine intensive kombinierte Pharmako- und Psychotherapie keine ausreichende Besserung erfahren haben, nicht vorenthalten werden darf.

Major depressive disorder (MDD) shows striking heterogeneity in both symptoms and underlying pathophysiology, and the absence of biologically grounded subtypes often results in a prolonged trial-and-error process when selecting effective treatments. This has motivated efforts to identify biomarkers that may predict individual treatment responses. Although mirtazapine is widely used and its efficacy is well established in clinical settings, neuroscientific studies on its treatment response remain limited relative to other antidepressants. To address this gap, this study examined pre-treatment pathophysiological neural features associated with subsequent response to mirtazapine. Sixty-seven individuals with MDD underwent functional magnetic resonance imaging during a conditioned reward task and then received monotherapy with mirtazapine or one of two comparator antidepressants (agomelatine or a selective serotonin reuptake inhibitor). Mirtazapine responders demonstrated increased pre-treatment activation in core components of the mesolimbic dopaminergic pathway, particularly the ventral tegmental area and ventral striatum, as well as in prefrontal and functionally connected regions implicated in reward evaluation, reward-related behavioral inhibition, and reward-based decision-making. Importantly, many of these response-related activations were specific to the mirtazapine group. These findings suggest that altered engagement of mesolimbic dopaminergic pathways and prefrontal regulatory networks during reward processing may characterize an MDD subtype responsive to mirtazapine, and that such patterns may serve as biomarkers for identifying patients likely to benefit from this treatment.

Abstract The aim of this project is the validation of genomic and non-genomic biomarkers for predicting antidepressant treatment outcome to identify biologically more homogenous subgroups of patients that might benefit from specific treatments targeting the identified biomarker system. Based on previous findings, we focused on the stress regulation gene FKBP5 for the selection of the genomic biomarkers and on a set of 41 cytokines/chemokines for defining immunological biomarkers. 307 inpatients hospitalized for treating a major depressive episode were included, who participated in the MARS/OptiMD study. MARS/OptiMD is an open-label multicentric treatment study conducted at four clinical centers in Germany. Biomarkers were extracted from DNA, RNA, and serum samples collected after study inclusion. Antidepressant treatment outcome was evaluated weekly by trained personal with the 21-items Hamilton Depression Rating scale (HAMD-21). Primary endpoint in this analysis was response after six weeks of treatment defined as a 50% HAMD-21 reduction compared with baseline. Replicating our previous findings with suggestive evidence, we observed that reduced FKBP5 expression was associated with response with approaching significance, and this trend was moderated by the FKBP5 genotype (rs1360780). Using Illumina EPIC Methylation BeadChips, we identified 67 DNA methylation markers located within the boundaries of the FKBP5 gene. A principal component analysis revealed five vectors with two (vector 1 and vector 2) showing a robust positive association between higher methylation levels and antidepressant treatment response. Again, these effects were moderated by the rs1360780 genotype. Among 41 cytokines/chemokines, six markers showed an association with treatment response with the strongest effect observed for interleukin 13. For interleukin 3, a trend was found towards an association with treatment response that was moderated by the individual CRP level as marker of the inflammation status. A combined analysis of both types of biomarkers, genomic and immunological, suggests that the observed effects on treatment outcome are independently from each other. Our results confirm and extend previous findings on the prominent role of genomic FKBP5 biomarkers, and partly also of cytokines/chemokine biomarkers, for predicting antidepressant treatment outcome in depression. Importantly, these effects are moderated by person factors like the FKBP5 genotype and the individual inflammation status, pointing to a suitability of these markers in identifying subgroups of patients that might benefit from personalized treatments targeting the associated biomarker systems.

Background: A better understanding of neurobiological mechanisms behind clinical depression and optimization of pharmacological treatment options remain enormous challenges. Early subtyping of depression might be achieved by discovering reliable trait markers or by early detection of changes in potential state markers, for example during the first days of antidepressant treatment. Objective: The primary objective of this trial was to explore early neurobiological dynamics during the first week of antidepressant treatment within the same drug-naïve inpatients in a large deep-phenotyping exploration applying various measurement modalities as described below. Methods: A longitudinal deep-phenotyping experimental design involved holistic measurements of various markers with state-of-the-art technology over five axes of investigation: MR neuroimaging, dexamethasone/CRH-testing, gut microbiome composition, inflammatory proteome and lipidomics. Therapy during these measurements was controlled and standardized by conducting a double-blind, randomized parallel-group design with four balanced arms during the first seven days of medication that encompassed three common first-line, yet pharmacologically distinguishable, antidepressants (escitalopram, mirtazapine, agomelatine) or placebo. The complete trial period has been 60 days including a third major longitudinal point of investigation at the end of trial. An additional control cohort with matched healthy volunteers was participating in the same set of investigations as patients at baseline, except dexamethasone/CRH-testing. Trial status: This trial has extensively served two subprojects of the German National Research Consortium OptiMD. It has been registered at the European Clinical Trials Register with identifier 2013-003370-27 and was initiated in January 2016. Recruitment of 70 inpatients and 25 healthy participants has been completed in August 2021 without any known harms in regard to study participation. Collection of data is still ongoing and hence, databases are not yet closed. Analyses of first complete datasets have begun and we hope that our deep-phenotyping exploration might contribute to new perspectives on clinical depression and its treatment. ### Competing Interest Statement Authors AH, GL, UD, AP and AG received compensation for their research contribution to this trial from TB. We acknowledge their valuable ongoing support and contribution to this research. TB received compensation for patient participation in co-enrollment trials FZPE PD-CAN and OptiMD SP5. Compensation for participating patients in SP5 was provided by OG. AH and AG are part-time employees at microBIOMix GmbH, Regensburg, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. ### Clinical Trial EudraCT number: 2013-003370-27 ### Funding Statement A major part of this investigator-initiated clinical trial has been supported by a grant from the 'Bundesministerium für Bildung und Forschung' (BMBF, German Federal Ministry of Education and Research) within the German research consortium 'Novel Strategies for Optimized Treatment of Depression' (OptiMD) as part of the national program 'Forschungsnetz für psychische Erkrankungen' (FZPE, Research Network for Mental Disorders) with grant number 01 EE1401B ('Förderkennzeichen'). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Study protocol, patient information sheets, and informed consent forms were approved on 20 May 2015 by the 'Ethikkommission bei der Universität Regensburg' (institutional ethics committee, Regensburg, Germany) and given approval number 15-111-0075. The trial was also registered with and approved by local district authorities and conducted in accordance with local legislation and institutional requirements. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Reliable de-identification of participant data is not truly possible for many datasets of this deep-phenotyping trial. For example, microbiome composition provides a fairly unique biomolecular fingerprint for each participant that tends to remain relatively stable over longer periods of time. Hence, the datasets of this study will not be publicly available due to concerns regarding participant anonymity. Reasonable requests for access to specific datasets should be directed to the corresponding author. We will support ethically sound and reasonable requests for collaboration.

Depressive Disorders in Adolescence: Current State of Studies Concerning the Microbiota-Gut-Brain Axis Abstract. Depressive disorders increase during adolescence and often lead to significant impairment in affected individuals - despite treatment. Current research efforts aim to further investigate the pathophysiology of depression, considering the influence of gut microbiota on the gut-brain axis. The present narrative review outlines the current state of studies of the microbiota-gut-brain axis in depressive disorders as well as the direct and indirect interactions in adolescence. Besides providing promising results from animal studies, studies on the microbiota-gut-brain axis in adults suffering from depressive disorders are growing steadily. In depressed adolescents, however, the study situation is still marginal, making a recommendation for the supplementation of probiotics and prebiotics in depressed children and adolescents impossible according to the current state of research. Against the background of a very limited number of studies involving adolescents with depressive disorders, the interactive role of the microbiota-gut-brain axis in adolescent development should receive special attention in future research projects.

Zusammenfassung. Im Verlauf der Adoleszenz nehmen depressive Störungen zu und führen oft trotz Behandlung zu deutlichen Einschränkungen bei den Betroffenen. Aktuelle Forschungsbemühungen haben sich zum Ziel gesetzt, die Pathophysiologie der Depression vor dem Hintergrund des Einflusses der Darmmikrobiota auf die Darm-Hirn-Achse näher zu untersuchen. Im Rahmen dieser narrativen Übersichtsarbeit zur aktuellen Studienlage der Mikrobiota-Darm-Hirn-Achse bei depressiven Störungen in der Adoleszenz werden die direkten und indirekten Wechselwirkungen erläutert und ein besonderer Fokus auf den Zeitraum der Adoleszenz gelegt. Neben vielversprechenden Ergebnissen aus tierexperimentellen Studien wächst die Studienlage bei depressiven Erwachsenen zur Mikrobiota-Darm-Hirn-Achse stetig. Bei depressiven Adoleszenten ist die Studienlage allerdings noch marginal, sodass nach aktuellem Forschungsstand noch keine Empfehlung für die Supplementation von Probiotika und Präbiotika bei depressiven Kindern und Jugendlichen ausgesprochen werden kann. Aufgrund der sehr begrenzten Studienlage bei Adoleszenten mit depressiven Störungen sollte auf die interaktive Rolle der Mikrobiota-Darm-Hirn-Achse in der adoleszenten Entwicklung bei zukünftigen Forschungsvorhaben ein besonderer Fokus gelegt werden.

Background:Neurosteroids have recently gained in interest as a treatment strategy for affective disorders. Etifoxine is known for its dual mode of action, one of which is to stimulate endogenous neurosteroid synthesis. The gut microbiome has been studied in affective disorders, but it has not been investigated in the context of human etifoxine or neurosteroid interventions.Methods:We performed a crossover study with 36 healthy male volunteers who received etifoxine versus alprazolam and placebo in a balanced Williams design. Participants were randomized into six sequences and went through three 5-day treatments followed by wash-out phases of 9 days. Bacterial compositions in stool samples were determined by high-throughput 16S rRNA amplicon sequencing.Results:Gut microbiome analyses revealed no relevant effects between treatments with respect to alpha and beta diversity. Differential abundance analyses yielded etifoxine treatment as the only effect related to changes in microbial features with reductions of Faecalibacterium duncaniae, Roseburia hominis and Lactobacillus rogosae (i.e., Bacteroides galacturonicus).Conclusion:Here we report on the first human investigation of the gut microbiome with short-term etifoxine intervention. Differences in diversity and compositional structure of the microbiome were more likely due to between- subject effects rather than medication. However, five-day treatment with etifoxine reduced the abundance of a few bacterial species. These species are currently seen as beneficial components of a healthy intestinal microbiome. This reduction in abundances may be related to elevated endogenous neurosteroids.

The molecular pathomechanisms of major depressive disorder (MDD) are still not completely understood. Here, we follow the hypothesis, that mitochondria dysfunction which is inevitably associated with bioenergetic disbalance is a risk factor that contributes to the susceptibility of an individual to develop MDD. Thus, we investigated molecular mechanisms related to mitochondrial function in induced neuronal progenitor cells (NPCs) which were reprogrammed from fibroblasts of eight MDD patients and eight non-depressed controls. We found significantly lower maximal respiration rates, altered cytosolic basal calcium levels, and smaller soma size in NPCs derived from MDD patients. These findings are partially consistent with our earlier observations in MDD patient-derived fibroblasts. Furthermore, we differentiated MDD and control NPCs into iPS-neurons and analyzed their passive biophysical and active electrophysiological properties to investigate whether neuronal function can be related to altered mitochondrial activity and bioenergetics. Interestingly, MDD patient-derived iPS-neurons showed significantly lower membrane capacitance, a less hyperpolarized membrane potential, increased Na + current density and increased spontaneous electrical activity. Our findings indicate that functional differences evident in fibroblasts derived from MDD patients are partially present after reprogramming to induced-NPCs, could relate to altered function of iPS-neurons and thus might be associated with the aetiology of major depressive disorder.

Key Points Question Does 6 weeks of minocycline treatment as add-on to standard antidepressant treatment reduce depressive symptoms in patients with treatment-resistant depression? Findings In this randomized clinical trial of 168 patients with treatment-resistant depression, 6 weeks of minocycline treatment did not show a statistically significant advantage compared with placebo on the overall course of depressive symptoms. Meaning The findings of this randomized clinical trial suggest the need for more effective therapeutic interventions and biomarkers in this heterogeneous clinical condition.

The prevalence and public health burden of chronic heart failure (CHF) in Europe is steadily increasing mainly caused by the ageing population and prolonged survival of patients with CHF. Frequent hospitalizations, high morbidity and mortality rates, and enormous healthcare costs contribute to the health-related burden. However, multidisciplinary frameworks that emphasize effective long-term management and the psychological needs of the patients are sparse. The present position paper endorsed by the European Association of Preventive Cardiology (EAPC) provides a comprehensive overview on the scientific evidence of psychosocial aspects of heart failure (HF). In order to synthesize newly available information and reinforce best medical practice, information was gathered via literature reviews and consultations of experts. It covers the evidence for aetiological and prospective psychosocial risk factors and major underlying psycho-biological mechanisms. The paper elucidates the need to include psychosocial aspects in self-care concepts and critically reviews the current shortcomings of psychotherapeutic and psycho-pharmacological interventions. It also highlights the need for involvement of psychological support in device therapy for patients with HF and finally calls for better palliative care in the final stage of HF progression.

Major depression is a complex disease and-among others, inflammation appears to play an important role in its pathophysiology. In this study, we investigated a broad range of cytokines in depressed patients. Plasma levels of interleukin (IL)-12/ IL-23p40, IL-15, IL-16, IL-17A, IL-1α, IL-7, tumor necrosis factorβ and vascular endothelial growth factor were compared in 48 patients suffering from major depression before, after one and after six weeks of antidepressive treatment in relation to therapy response. Interestingly, the level of IL-17A turned out to rise significantly in the non-responder group compared to responder during antidepressive treatment. IL-17A is a pro-inflammatory cytokine that initiates the production of other cytokines, thereby inducing and mediating immune response. It is also involved in allergic and autoimmune-related diseases. The database investigating the role of IL-17A in major depressive disorder has grown within the last few years comparing levels of this cytokine in depressed patients versus healthy subjects. However, little is known about the expression of IL-17A during the course of antidepressive treatment. In summary, our study provides valuable evidence that this cytokine might serve as a marker of therapy resistance to antidepressants.

The pandemic spread of the corona virus SARS-CoV-2 has even-handedly shattered national and international health systems and economies almost in an instant. As numbers of infections and COVID-19-related deaths rise from day to day, fears and uncertainties on how to deal with this unknown threat are extremely present both for individuals and societies as a whole. In this manuscript, we aim to exemplarily describe the bullet points concerning (a) the internal risk management, (b) the organizational and structural changes, and (c) the communicational strategies applied in a Psychiatric University Hospital in the Southern part of Germany. The authors are well aware about the fact that almost none of these considerations may be considered as evidence-based at the moment. However, the authors trust that these reflections and experiences may be useful as an orientation for similar risk constellations in other afflicted countries due to the temporal delay of the pandemic course.

ZUSAMMENFASSUNG Gegenstand und Ziel Die vorliegende Studie zeigt einen alternativen Weg zur Operationalisierung des Begriffs „regionale Pflichtversorgung“ in der stationären Psychiatrie und Psychotherapie auf. Material und Methoden In einer explorativen Analyse von 9659 Behandlungsfällen von psychiatrischen Fachabteilungen an 3 Standorten wurden aus Routinedaten gewonnene Kennzahlen hinsichtlich ihrer Eignung zur Abbildung des Begriffs untersucht. Ergebnisse Im Abgleich mit einem Expertenrating konnten hohe Übereinstimmungswerte vor allem bei denjenigen Parametern gefunden werden, die den Aspekt der Vollversorgung („Diagnosespektrum“), der Notfallversorgung („Aufnahmezeit“) und den Aspekt der Versorgungsleistung in der Region („Hauptversorgungsgebiet“) abbilden. Schlussfolgerung Als Vorteile der Methodik werden die aufwandsneutrale Erhebungs- und Überprüfungsmechanismen sowie die vergleichsweise hohe Objektivität und Reliabilität der generierten Kennzahlen gesehen. Zudem eröffnet dieses Vorgehen die Perspektive einer Generalisierbarkeit des Begriffs der Pflichtversorgung auf andere Fachabteilungen ohne die psychiatriespezifische Besonderheit der gerichtlichen Unterbringung. Aufgrund der geringen Anzahl der betrachteten Standorte bedarf es jedoch zwingend weiterer konfirmatorischer, multizentrischer Untersuchungen. Klinische Relevanz Ziel kann dabei die Generierung eines Komplexindex sein, welcher eine valide Abbildung des Konstrukts „regionale Pflichtversorgung“ erlaubt und damit die Basis für eine adäquate und leistungsgerechte Ressourcenzuweisung an die Kliniken vor dem Hintergrund der gesundheitspolitischen Bestrebungen für eine Neuordnung der Personalbemessung in den entsprechenden Fachgebieten schafft.

Depression is a chronic disease with a complex multifactorial and still not fully clarified etiology. Due to new insights after recent investigations of the microbiota-gut-brain (MGB) axis, a relationship between a disrupted gut microbiota composition and the probability to develop a depression can be assumed. This hypothesis is supported by evidence that there is a strong communication between gut microbiota and the central nervous system (CNS) and that this communication is mediated through the MGB axis. Apparently, this bidirectional axis can be modulated by environmental factors, such as stress, pharmaceuticals (in particular antibiotics) and dietary habits. Moreover, modulation of this axis can also result in mood alterations. As the hypothalamic-pituitary-adrenal (HPA) axis is a key element regulating the MGB axis and is also related to the pathophysiology of depression, it is important to understand the relationship between both biological systems. An English language literature search was conducted using the biomedical database PubMed. We used combined terms, such as "gut microbiota", "depression", "hypothalamic-pituitary-adrenal axis" or "microbiota-gut-brain axis". The current literature supports the idea that the MGB axis has an impact on the risk to develop depression and that stress modulation through the HPA axis plays a key role in this context.

ZUSAMMENFASSUNG Gegenstand und Ziel: Analysen des Dickdarm-Mikrobioms sind ein international zunehmend intensiver untersuchter Forschungsschwerpunkt. Die zahlreichen Schwierigkeiten solcher Studien sind oft nicht bekannt, worauf hier vermehrt aufmerksam gemacht werden soll. Antidepressiva und Antibiotika zeigen teils ähnliche Wirkmechanismen, weshalb erneut psychiatrische Indikationen für Antibiotika geprüft werden. Vor diesem Hintergrund zeigen wir Daten einer Feldbeobachtung an der Universität Regensburg. Material und Methoden: 179 Teilnehmer spendeten eine Stuhlprobe und füllten das Regensburg Microbiome Questionnaire (ReMBiQ) aus. Das bakterielle Mikrobiom aller Stuhlproben wurde mittels 16S-rRNA-Hochdurchsatz-Sequenzierung analysiert. Anhand des ReMBiQ wurde eine Subkohorte ausgewählt: Zu einer Teilnehmerin mit seit 18 Monaten behandelter MDR-Tuberkulose wurden 4 gesunde Kontrollen anhand zahlreicher und für das Dickdarm-Mikrobiom relevanter Kriterien ausgewählt. Ergebnisse: Mikrobiomtypische Parameter wie Alpha- und Beta-Diversität grenzten die Teilnehmerinnen innerhalb der Subkohorte klar voneinander ab. Hierbei half auch die Messung absoluter Bakterienmengen mittels spike-in-based calibration to total microbial load (SCML). Insgesamt fiel im Vergleich insbesondere eine deutliche Zunahme der Gattung Bacteroides auf, die mit 94,5 % dominierte. Schlussfolgerungen: Unterschiedliche Ergebnisse bei gleichen oder ähnlichen, starken Eingriffen im Dickdarm, verdeutlichen die Notwendigkeit strenger methodischer Standards. Dies gilt insbesondere für die Beobachtung vergleichsweise kleiner Effektgrößen in den Neurowissenschaften. Klinische Relevanz: Die neurowissenschaftliche Bewertung des Dickdarm-Mikrobioms unter kombiniert antidepressiv-antimikrobieller Therapie wird wichtige Hinweise auf die Wirksamkeit neuer Therapieformen liefern.

Depression is a chronic disease with a complex multifactorial and still not fully clarified etiology. Due to new insights after recent investigations of the microbiota-gut-brain (MGB) axis, a relationship between a disrupted gut microbiota composition and the probability to develop a depression can be assumed. This hypothesis is supported by evidence that there is a strong communication between gut microbiota and the central nervous system (CNS) and that this communication is mediated through the MGB axis. Apparently, this bidirectional axis can be modulated by environmental factors, such as stress, pharmaceuticals (in particular antibiotics) and dietary habits. Moreover, modulation of this axis can also result in mood alterations. As the hypothalamic-pituitary-adrenal (HPA) axis is a key element regulating the MGB axis and is also related to the pathophysiology of depression, it is important to understand the relationship between both biological systems. An English language literature search was conducted using the biomedical database PubMed. We used combined terms, such as \"gut microbiota\", \"depression\", \"hypothalamic-pituitary-adrenal axis\" or \"microbiota-gut-brain axis\". The current literature supports the idea that the MGB axis has an impact on the risk to develop depression and that stress modulation through the HPA axis plays a key role in this context.

Zusammenfassung Depression ist eine chronische Erkrankung mit einer komplexen multifaktoriellen und immer noch nicht vollständig verstandenen Ätiologie. Aufgrund der Erkenntnisse neuerer Untersuchungen der Mikrobiota-Darm-Hirn(MDH)-Achse kann ein Zusammenhang zwischen einer gestörten Zusammensetzung der Darmmikrobiota und der Wahrscheinlichkeit, eine Depression zu entwickeln, angenommen werden. Diese Vermutung stützt sich auf das Wissen, dass eine Kommunikation zwischen der Darmbesiedelung und dem zentralen Nervensystem (ZNS) existiert und dass eine derartige Kommunikation durch die MDH-Achse vermittelt wird. Offenbar wird diese bidirektionale Achse durch Umweltfaktoren wie Stress, Pharmaka (insbesondere Antibiotika) und Ernährungsgewohnheiten beeinflusst. Eine Modulation dieser Achse kann auch Veränderungen der Stimmungslage verursachen. Da die Hypothalamus-Hypophysen-Nebennierenrinden(HHN)-Achse ein Schlüsselelement der MDH-Achse darstellt und auch mit der Pathophysiologie der Depression im Zusammenhang steht, ist es wichtig, deren diesbezügliche Verbindungen zu verstehen. Wir führten daher eine Literaturrecherche englischsprachiger wissenschaftlicher Literatur unter Nutzung der biomedizinischen Datenbasis PubMed durch. Dazu wurden kombinierte Begriffe wie „gut microbiota“, „depression“, „hypothalamic-pituitary-adrenal axis“ oder „microbiota-gut-brain axis“ verwendet. Es zeigt sich, dass die entsprechende Literatur die These, dass die MDH-Achse das Risiko, eine Depression zu entwickeln, beeinflussen kann, stützt, wobei eine Stressmodulation durch die HHN-Achse hierbei eine Schlüsselrolle spielt.

Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial dysfunction in adult human skin fibroblasts, which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and adenosine triphosphate (ATP)-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance, which is associated with the molecular pathophysiology of MDD. The observed alterations in the oxidative phosphorylation system (OXPHOS) and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.

On Earth, we find an amazing number of creatures living together. Each creature is unique. All of them interact together, without borders, making this world—our world—a beautiful place to live. Bacteria are tiny organisms present almost everywhere, including on and in our bodies. Gut bacteria have a strong communication with the brain. A correct communication between gut bacteria and the brain is important for adequate mental health. Situations that damage our gut bacteria are able to harm our brains. Moreover, mental stress can damage bacteria living in the gut. We need to take care of our gut bacteria. A balanced diet, including fish, vegetables, cereals, fruits, and water can help our gut bacteria to be healthy. Healthy gut bacteria will have a positive effect on the brain and our moods. “Happy gut bacteria” will help us to have “happy brains.”