Aberrant neuronal connectivity and network activity of neurons derived from patients with idiopathic schizophrenia.

Schizophrenia (SCZ) is a psychiatric disorder with a strong genetic determinant. A major hypothesis to explain disease aetiology comprises synaptic dysfunction associated with excitatory-inhibitory imbalance of synaptic transmission, ultimately contributing to impaired network oscillation and cognitive deficits associated with the disease. Here, we studied the morphological and functional properties of a highly defined co-culture of GABAergic and glutamatergic neurons derived from induced pluripotent stem cells (iPSC) from patients with idiopathic SCZ. Our results indicate upregulation of synaptic genes and increased excitatory synapse formation on GABAergic neurons in co-cultures. In parallel, we observed decreased lengths of axon initial segments, concordant with data from postmortem brains from patients with SCZ. In line with increased synapse density, patch-clamp analyses revealed markedly increased spontaneous excitatory postsynaptic currents (EPSC) recorded from GABAergic SCZ neurons. Finally, MEA recordings from neuronal networks indicate increased strength of network activity, potentially in response to altered synaptic transmission and E-I balance in the co-cultures. In conclusion, our results suggest selective deregulation of neuronal activity in SCZ samples, providing evidence for altered synapse formation and synaptic transmission as a potential base for aberrant network synchronization.

Perspectives on physician-assisted suicide in mental healthcare: results of a survey of physicians and medical students.

BACKGROUND: Physician-assisted suicide (PAS) is typically associated with serious physical illnesses that are prevalent in palliative care. However, individuals with mental illnesses may also experience such severity that life becomes intolerable. In February 2020, the previous German law prohibiting PAS was repealed. Patients with severe mental illnesses are increasingly likely to approach physicians with requests for PAS. AIMS: To explore the ethical and moral perspectives of medical students and physicians when making individual decisions regarding PAS. METHOD: An anonymised digital survey was conducted among medical students and physicians in Germany. Participants were presented with a case vignette of a chronically depressed patient requesting PAS. Participants decided on PAS provision and assessed theoretical arguments. We employed generalised ordinal regression and qualitative analysis for data interpretation. RESULTS: A total of N = 1478 participants completed the survey. Of these, n = 470 (32%) stated that they would refuse the request, whereas n = 582 (39%) would probably refuse, n = 375 (25%) would probably agree and n = 57 (4%) would definitely agree. Patient-centred arguments such as the right to self-determination increased the likelihood of consent. Concerns that PAS for chronically depressed patients might erode trust in the medical profession resulted in a decreased willingness to provide PAS. CONCLUSIONS: Participants displayed relatively low willingness to consider PAS in the case of a chronically depressed patient. This study highlights the substantial influence of theoretical medical-ethical arguments and the broader public discourse, underscoring the necessity of an ethical discussion on PAS for mental illnesses.

N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial.

Background and Hypothesis: Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients. Study Design: In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months. Study Results: While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ±â€…13.4%, PSM + NAC: 72.7 ±â€…13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ±â€…15.3%, PSM + PLC: 39.0 ±â€…17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups. Conclusions: The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.

'The mirror of the soul?' Inferring sadness in the eyes.

The eyes are widely regarded as the mirror of the soul, providing reliable nonverbal information about drives, feelings, and intentions of others. However, it is unclear how accurate emotion recognition is when only the eyes are visible and whether inferring of emotions is altered across healthy adulthood. To fill this gap, the present piece of research was directed at comparing the ability to infer basic emotions in two groups of typically developing females that differed in age. We set a focus on females seeking group homogeneity. In a face-to-face study, in a two-alternative forced choice paradigm (2AFC), participants had to indicate emotions for faces covered by masks. The outcome reveals that although the recognition pattern is similar in both groups, inferring sadness in the eyes substantially improves with age. Inference of sadness is not only more accurate and less variable in older participants, but also positively correlates with age from early through mid-adulthood. Moreover, reading sadness (and anger) is more challenging in the eyes of male posers. A possible impact of poser gender and cultural background, both in expressing and inferring sadness in the eyes, is highlighted.

Reading language of the eyes in female depression.

Aberrations in non-verbal social cognition have been reported to coincide with major depressive disorder. Yet little is known about the role of the eyes. To fill this gap, the present study explores whether and, if so, how reading language of the eyes is altered in depression. For this purpose, patients and person-by-person matched typically developing individuals were administered the Emotions in Masked Faces task and Reading the Mind in the Eyes Test, modified, both of which contained a comparable amount of visual information available. For achieving group homogeneity, we set a focus on females as major depressive disorder displays a gender-specific profile. The findings show that facial masks selectively affect inferring emotions: recognition of sadness and anger are more heavily compromised in major depressive disorder as compared with typically developing controls, whereas the recognition of fear, happiness, and neutral expressions remains unhindered. Disgust, the forgotten emotion of psychiatry, is the least recognizable emotion in both groups. On the Reading the Mind in the Eyes Test patients exhibit lower accuracy on positive expressions than their typically developing peers, but do not differ on negative items. In both depressive and typically developing individuals, the ability to recognize emotions behind a mask and performance on the Reading the Mind in the Eyes Test are linked to each other in processing speed, but not recognition accuracy. The outcome provides a blueprint for understanding the complexities of reading language of the eyes within and beyond the COVID-19 pandemic.

On assessing trait rumination using the Ruminative Response Scale.

Introduction: This study explores the stability of scores on psychometrically validated trait questionnaires over time. We illustrate potential pitfalls through a larger study that used the Ruminative Response Scale (RRS) to categorize participants prior to study inclusion into two groups based on their habitual tendency to ruminate. Surprisingly, when we re-administered the RRS at the start of an experimental session, significant score changes occurred, resulting in participants shifting between the two groups. Methods: To address this, we modified our recruitment process, aiming to reduce careless responses, including an online RRS assessment a week before the lab appointment. We analyzed the different samples prior to and after changing the recruitment procedure, as well as the total sample regarding the psychometric properties of the RRS. We also explored various indices to identify and predict score changes due to careless responding; however, only a subgroup of participants was successfully identified. Results: Our findings suggest that Mahalanobis distances are effective for identifying substantial score changes, with baseline state rumination emerging as a marginally significant predictor. Discussion: We discuss the importance of conducting manipulation checks and offer practical implications for research involving psychometrically validated trait questionnaires.

Neural correlates of stress-reactive rumination in depression - The role of childhood trauma and social anxiety.

Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N = 55 patients currently suffering from MDD and n = 42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the Cognitive Control Network (CCN) was measured via functional near-infrared spectroscopy (fNIRS). The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated prefrontal hypoactivity during stress and extends the research toward specific subtypes of depression.

Larger putamen in individuals at risk and with manifest bipolar disorder.

BACKGROUND: Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations. METHODS: In 410 male and female participants aged 17-35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites. RESULTS: Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake. CONCLUSIONS: Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.

[Implementation of an Open Door Policy on Two Acute Care Units]. / Implementierung eines Konzepts der offenen Türen auf zwei psychiatrischen Akutstationen an zwei Kliniken.

BACKGROUND: Since the amendments to the Baden-Württemberg Psychiatric Assistance Act, psychiatric patients who are treated involuntarily can be admitted to open wards. As a result, a comprehensive research project was carried out to implement an open-door policy. This work evaluates the attitudes of patients and therapeutic teams. METHODS: Over the course of a year, 8 focus groups with 6 to 11 participants were conducted with patients and staff before and at the end of the intervention phase and analyzed qualitatively. RESULTS: The concept of open doors was received positively. The staff raised safety concerns whereas on the patient side the door status seemed to be of limited relevance regarding the experience of autonomy or stigmatization. DISCUSSION: The elaboration of conflict issues allows a further development of specific concepts towards the implementation of open doors on psychiatric acute wards.

Dynamic brain communication underwriting face pareidolia.

Face pareidolia is a tendency to seeing faces in nonface images that reflects high tuning to a face scheme. Yet, studies of the brain networks underwriting face pareidolia are scarce. Here, we examined the time course and dynamic topography of gamma oscillatory neuromagnetic activity while administering a task with nonface images resembling a face. Images were presented either with canonical orientation or with display inversion that heavily impedes face pareidolia. At early processing stages, the peaks in gamma activity (40 to 45 Hz) to images either triggering or not face pareidolia originate mainly from the right medioventral and lateral occipital cortices, rostral and caudal cuneus gyri, and medial superior occipital gyrus. Yet, the difference occurred at later processing stages in the high-frequency range of 80 to 85 Hz over a set of the areas constituting the social brain. The findings speak rather for a relatively late neural network playing a key role in face pareidolia. Strikingly, a cutting-edge analysis of brain connectivity unfolding over time reveals mutual feedforward and feedback intra- and interhemispheric communication not only within the social brain but also within the extended large-scale network of down- and upstream regions. In particular, the superior temporal sulcus and insula strongly engage in communication with other brain regions either as signal transmitters or recipients throughout the whole processing of face-pareidolia images.

Microglia-neuron interactions in schizophrenia.

Multiple lines of evidence implicate increased neuroinflammation mediated by glial cells to play a key role in neurodevelopmental disorders such as schizophrenia. Microglia, which are the primary innate immune cells of the brain, are crucial for the refinement of the synaptic circuitry during early brain development by synaptic pruning and the regulation of synaptic plasticity during adulthood. Schizophrenia risk factors as genetics or environmental influences may further be linked to increased activation of microglia, an increase of pro-inflammatory cytokine levels and activation of the inflammasome resulting in an overall elevated neuroinflammatory state in patients. Synaptic loss, one of the central pathological hallmarks of schizophrenia, is believed to be due to excess removal of synapses by activated microglia, primarily affecting glutamatergic neurons. Therefore, it is crucial to investigate microglia-neuron interactions, which has been done by multiple studies focusing on post-mortem brain tissues, brain imaging, animal models and patient iPSC-derived 2D culture systems. In this review, we summarize the major findings in patients and in vivo and in vitro models in the context of neuron-microglia interactions in schizophrenia and secondly discuss the potential of anti-inflammatory treatments for the alleviation of positive, negative, and cognitive symptoms.

Validation of the Self-Report Version of the German Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Scale (SWAN-DE-SB).

Adults with attention-deficit/hyperactivity disorder (ADHD) experience impairing levels of inattention and/or hyperactivity-impulsivity, while individuals without ADHD experience these symptoms to a lesser extent. Yet, ADHD self-report scales so far hardly captured continuous distributions across the general population. In addition, they focused on weaknesses and ignored strengths. To address these shortcomings, we present here the Strengths and Weaknesses of ADHD and Normal-Behavior Scale Self-Report (SWAN-DE-SB). The normal distribution of the data collected and the scale's internal consistency, and factorial and convergent validity were assessed using data from a general population sample. Its clinical utility was evaluated by comparing scores from a clinical sample and a sample of individuals without ADHD and by calculating optimal cut-off values for specificity and sensitivity. The SWAN-DE-SB demonstrated normal distribution of the data collected, high internal consistency, and factorial and convergent validity. It reliably discriminated individuals with and without ADHD, with high specificity and sensitivity. It should therefore be considered a psychometrically convincing measure to assess strengths and weaknesses of ADHD symptoms and normal behavior in clinical and general population samples.

Trait-dependent effects of theta burst stimulation after psychosocial stress: a sham-controlled study in healthy individuals.

OBJECTIVE: Previous studies suggest that theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising approach to modulate stress-reactive rumination and the associated psychophysiological stress response. Crucially, individuals showing higher levels of trait rumination might benefit more from prefrontal stimulation. METHODS: In this sham-controlled study, 127 healthy individuals, with varying ruminative tendencies, received a single-session of intermittent TBS (iTBS), continuous TBS (cTBS) or sham TBS (sTBS) over the left DLPFC before being confronted with a Trier Social Stress Test. RESULTS: Results showed significant TBS effects on salivary cortisol as a function of trait rumination. cTBS, as compared to sTBS and iTBS, resulted in an attenuated stress-induced cortisol response in high compared to low trait ruminators. Although independent of trait rumination levels, cTBS showed positive effects on stress-related changes in mood and, both cTBS and iTBS (versus sham) presented an enhanced heart rate recovery following the stressor. We found no evidence for (trait rumination-dependent) TBS effects on stress-reactive rumination, negative affect, subjective stress or heart rate variability. CONCLUSIONS: cTBS shows beneficial effects on certain measures of stress, especially in high trait ruminators. SIGNIFICANCE: These findings highlight the importance of accounting for individual differences when examining TBS effects.

[The German Center for Mental Health : Innovative translational research to promote prevention, targeted intervention and resilience]. / Das Deutsche Zentrum für Psychische Gesundheit : Innovative Translationsforschung zur Förderung von Prävention, zielgerichteter Intervention und Resilienz.

BACKGROUND: Due to the high disease burden, the early onset and often long-term trajectories mental disorders are among the most widespread diseases with growing significance. The German Center for Mental Health (DZPG) was established to enhance research conditions and expedite the translation of clinically relevant findings into practice. OBJECTIVE: The aim of the DZPG is to optimize mental healthcare in Germany, influence modifiable social causes and to develop best practice models of care for vulnerable groups. It seeks to promote mental health and resilience, combat the stigmatization associated with mental disorders, and contribute to the enhancement of treatment across all age groups. MATERIAL AND METHODS: The DZPG employs a translational research program that accelerates the translation of basic research findings into clinical studies and general practice. University hospitals and outpatient departments, other university disciplines, and extramural research institutions are working together to establish a collaboratively coordinated infrastructure for accelerated translation and innovation. RESEARCH PRIORITIES: The research areas encompass 1) the interaction of somatic and mental risk and resilience factors and disorders across the lifespan, 2) influencing relevant modifiable environmental factors and 3) based on this personalized prevention and intervention. CONCLUSION: The DZPG aims to develop innovative preventive and therapeutic tools that enable an improvement in care for individuals with mental disorders. It involves a comprehensive integration of experts with experience at all levels of decision-making and employs trilogue and participatory approaches in all research projects.

Neurocognitive function as outcome and predictor for prefrontal transcranial direct current stimulation in major depressive disorder: an analysis from the DepressionDC trial.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex might beneficially influence neurocognitive dysfunctions associated with major depressive disorder (MDD). However, previous studies of neurocognitive effects of tDCS have been inconclusive. In the current study, we analyzed longitudinal, neurocognitive data from 101 participants of a randomized controlled multicenter trial (DepressionDC), investigating the efficacy of bifrontal tDCS (2 mA, 30 min/d, for 6 weeks) in patients with MDD and insufficient response to selective serotonin reuptake inhibitors (SSRI). We assessed whether active tDCS compared to sham tDCS elicited beneficial effects across the domains of memory span, working memory, selective attention, sustained attention, executive process, and processing speed, assessed with a validated, digital test battery. Additionally, we explored whether baseline cognitive performance, as a proxy of fronto-parietal-network functioning, predicts the antidepressant effects of active tDCS versus sham tDCS. We found no statistically significant group differences in the change of neurocognitive performance between active and sham tDCS. Furthermore, baseline cognitive performance did not predict the clinical response to tDCS. Our findings indicate no advantage in neurocognition due to active tDCS in MDD. Additional research is required to systematically investigate the effects of tDCS protocols on neurocognitive performance in patients with MDD.

Young people at risk for developing bipolar disorder: Two-year findings from the multicenter prospective, naturalistic Early-BipoLife study.

Early identification and intervention of individuals with an increased risk for bipolar disorder (BD) may improve the course of illness and prevent long­term consequences. Early-BipoLife, a multicenter, prospective, naturalistic study, examined risk factors of BD beyond family history in participants aged 15-35 years. At baseline, positively screened help-seeking participants (screenBD at-risk) were recruited at Early Detection Centers and in- and outpatient depression and attention-deficit/hyperactivity disorder (ADHD) settings, references (Ref) drawn from a representative cohort. Participants reported sociodemographics and medical history and were repeatedly examined regarding psychopathology and the course of risk factors. N = 1,083 screenBD at-risk and n = 172 Ref were eligible for baseline assessment. Within the first two years, n = 31 screenBD at-risk (2.9 %) and none of Ref developed a manifest BD. The cumulative transition risk was 0.0028 at the end of multistep assessment, 0.0169 at 12 and 0.0317 at 24 months (p = 0.021). The transition rate with a BD family history was 6.0 %, 4.7 % in the Early Phase Inventory for bipolar disorders (EPIbipolar), 6.6 % in the Bipolar Prodrome Interview and Symptom Scale-Prospective (BPSS-FP) and 3.2 % with extended Bipolar At-Risk - BARS criteria). In comparison to help-seeking young patients from psychosis detection services, transition rates in screenBD at-risk participants were lower. The findings of Early-BipoLife underscore the importance of considering risk factors beyond family history in order to improved early detection and interventions to prevent/ameliorate related impairment in the course of BD. Large long-term cohort studies are crucial to understand the developmental pathways and long-term course of BD, especially in people at- risk.

Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features.

BACKGROUND: Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features. METHODS: Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar). RESULTS: For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11-0.361) and a balanced accuracy of 63.1% (95% CI 55.9-70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI -0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6-67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance. CONCLUSIONS: Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.

Prevalence of COVID-19 and Psychotropic Drug Treatment in Psychiatric In-patients in Germany in 2020: Results from a Nationwide Pilot Survey.

INTRODUCTION: In patients with a pre-existing mental disorder, an increased risk for a first manifestation of a psychiatric disorder in COVID-19 patients, a more severe course of COVID-19 and an increased mortality have been described. Conversely, observations of lower COVID-19 incidences in psychiatric in-patients suggested protective effects of psychiatric treatment and/or psychotropic drugs against COVID-19. METHODS: A retrospective multi-center study was conducted in 24 German psychiatric university hospitals. Between April and December 2020 (the first and partly second wave of COVID-19), the effects of COVID-19 were assessed on psychiatric in-patient care, the incidence and course of a SARS-CoV-2 infection, and treatment with psychotropic drugs. RESULTS: Patients (n=36,322) were admitted to the hospitals. Mandatory SARS-CoV-2 tests before/during admission were reported by 23 hospitals (95.8%), while 18 (75%) conducted regular testing during the hospital stay. Two hundred thirty-two (0.6%) patients were tested SARS-CoV-2-positive. Thirty-seven (16%) patients were receiving medical treatment for COVID-19 at the psychiatric hospital, ten (4.3%) were transferred to an intermediate/intensive care unit, and three (1.3%) died. The most common prescription for SARS-CoV-2-positive patients was for second-generation antipsychotics (n=79, 28.2%) and antidepressants (SSRIs (n=38, 13.5%), mirtazapine (n=36, 12.9%) and SNRIs (n=29, 10.4%)). DISCUSSION: Contrary to previous studies, our results showed a low number of infections and mortality in SARS-CoV-2-positive psychiatric patients. Several preventive measures seem effective to protect this vulnerable group. Our observations are compatible with the hypothesis of a protective effect of psychotropic drugs against COVID-19 as the overall mortality and need for specific medical treatment was low.

In situ fNIRS measurements during cognitive behavioral emotion regulation training in rumination-focused therapy: A randomized-controlled trial.

Repetitive negative thinking (RNT), including rumination, plays a key role in various psychopathologies. Although several psychotherapeutic treatments have been developed to reduce RNT, the neural correlates of those specific treatments and of psychotherapy in general are largely unknown. Functional near-infrared spectroscopy (fNIRS) offers the potential to investigate the neural correlates of psychotherapeutic techniques in situ. Therefore, in this study we investigated the efficacy and neural correlates of a fNIRS adapted Mindfulness-based Emotion Regulation Training (MBERT) for the treatment of depressive rumination in 42 subjects with major depressive disorder (MDD) in a cross-over designed randomized controlled trial. Using psychometric measures, subjective ratings and fNIRS, we analyzed in situ changes in depressive symptom severity, ruminative thoughts and cortical activity in the Cognitive Control Network (CCN). Our results show that MBERT is effective in treating depressive symptoms and rumination. On a neural level, we found consistently higher cortical activation during emotion regulation training compared to control trials in the bilateral inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). Furthermore, cortical oxygenation decreased from session to session in the bilateral DLPFC. The relevance of the results for the psychotherapeutic treatment of MDD as well as further necessary investigations are discussed.