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Abstract Objective Therapeutic alliance is often considered as a predictor for therapeutic success. This study explored dyadic synchrony of skin conductance response (SCR) during naturalistic therapeutic interactions and investigated its potential as an objective biomarker for predicting therapy effectiveness. Methods In this proof‐of‐concept study, skin conductance from both dyad members was continuously measured via wristbands during psychotherapy. Patients and therapists completed post‐session reports capturing their subjective appraisal of therapeutic alliance. Additionally, patients completed symptom questionnaires. Each therapeutic dyad was recorded twice in a follow‐up design. The first session of the follow‐up group was assessed for physiological synchrony (Single Session Index (SSI)). Therapy outcome was captured by the difference between symptom severity scores over time. Results SCR synchrony significantly predicted the outcome variable of change in patients' global severity index (GSI). High positive SCR concordance was linked to a reduction in patients' GSI, while negative or small positive SSI values were linked to an increase in patients' GSI. Conclusion The results demonstrate the presence of SCR synchrony in clinical interactions. Skin conductance response synchrony was a significant predictor for change in patients' symptom severity index, emphasizing its potential as an objective biomarker in the context of evidence‐based psychotherapy.

Abstract Background Suicidality, ranging from passive suicidal thoughts to suicide attempt, is common in major depressive disorder (MDD). However, relatively little is known about patient, illness and treatment characteristics in those with co-occurring MDD and suicidality, including the timing of and factors associated with the offset, continuation or reemergence of suicidality. Here, we present the background, rationale, design and hypotheses of the Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D) study, an investigator-initiated, observational study, funded by Janssen-Cilag GmbH. Methods/Results OASIS-D is an eight-site, six-month, cohort study of patients aged 18-75 hospitalized with MDD. Divided into three sub-studies and patient populations (PPs), OASIS-D will (i) systematically characterize approximately 4500 consecutively hospitalized patients with any form of unipolar depressive episode (PP1), (ii) evaluate the validity of the clinical diagnosis of moderate or severe unipolar depressive episode with the Mini-International Neuropsychiatric Interview (M.I.N.I.) and present suicidality (at least passive suicidal thoughts) present ≥ 48 h after admission with the Sheehan-Suicide Tracking Scale (S-STS), assessing also predictors of the diagnostic concordance/discordance of MDD in around 500 inpatients (PP2), and (iii) characterize and prospectively follow for 6 months 315 inpatients with a research-verified moderate or severe unipolar depressive episode and at least passive suicidal thoughts ≥ 48 h after admission, evaluating treatment and illness/response patterns at baseline, hospital discharge, 3 and 6 months. Exploratory objectives will describe the association between the number of days with suicidality and utilization of outpatient and inpatient care services, and structured assessments of factors influencing the risk of self-injurious behavior without suicidal intent, and of continuous, intermittent or remitted suicidality during the 6-month observation period. Conclusion Despite their frequency and clinical relevance, relatively little is known about patient and treatment characteristics of individuals with MDD and suicidality, including factors moderating and mediating the outcome of both MDD and suicidality. Results of the OASIS-D study are hoped to improve the understanding of the frequency, correlates and 6-month naturalistic treatment and outcome trajectories of different levels of suicidality in hospitalized adults with MDD and suicidality. Trial registration NCT04404309 [ClinicalTrials.gov]

IntroductionThere are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study.Material and methodsDuring the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively.Statistical analysisDescriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables.ResultsProbable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed.ConclusionsThe final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them.

Reliably diagnosing autism spectrum disorders (ASD) in adulthood poses a challenge to clinicians due to the absence of specific diagnostic markers. This study investigated the potential of interpersonal synchrony (IPS), which has been found to be reduced in ASD, to augment the diagnostic process. IPS was objectively assessed in videos of diagnostic interviews in a representative referral population from two specialized autism outpatient clinics. In contrast to the current screening tools that could not reliably differentiate, we found a significant reduction of IPS in interactions with individuals later diagnosed with ASD (n = 16) as opposed to those not receiving a diagnosis (n = 23). While these findings need to be validated in larger samples, they nevertheless underline the potential of digitally-enhanced diagnostic processes for ASD.

BackgroundTransition to psychosis is among the most adverse outcomes of clinical high-risk (CHR) syndromes encompassing ultra-high risk (UHR) and basic symptom states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse risk populations, including young patients with depressive syndromes.MethodsWe validated the previously described NAPLS-2 (North American Prodrome Longitudinal Study 2) calculator in 334 patients (26 with transition to psychosis) with CHR or recent-onset depression (ROD) drawn from the multisite European PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Patients were categorized into three risk enrichment levels, ranging from UHR, over CHR, to a broad-risk population comprising patients with CHR or ROD (CHR|ROD). We assessed how risk enrichment and different predictive algorithms influenced prognostic performance using reciprocal external validation.ResultsAfter calibration, the NAPLS-2 model predicted psychosis with a balanced accuracy (BAC) (sensitivity, specificity) of 68% (73%, 63%) in the PRONIA-UHR cohort, 67% (74%, 60%) in the CHR cohort, and 70% (73%, 66%) in patients with CHR|ROD. Multiple model derivation in PRONIA-CHR|ROD and validation in NAPLS-2-UHR patients confirmed that broader risk definitions produced more accurate risk calculators (CHR|ROD-based vs. UHR-based performance: 67% [68%, 66%] vs. 58% [61%, 56%]). Support vector machines were superior in CHR|ROD (BAC = 71%), while ridge logistic regression and support vector machines performed similarly in CHR (BAC = 67%) and UHR cohorts (BAC = 65%). Attenuated psychotic symptoms predicted psychosis across risk levels, while younger age and reduced processing speed became increasingly relevant for broader risk cohorts.ConclusionsClinical-neurocognitive machine learning models operating in young patients with affective and CHR syndromes facilitate a more precise and generalizable prediction of psychosis. Future studies should investigate their therapeutic utility in large-scale clinical trials.

Abstract Background Quantifying depression mainly relies on the use of depression scales, and understanding their factor structure is crucial for evaluating their validity. Methods This post-hoc analysis utilized prospectively collected data from a naturalistic study of 1014 inpatients with major depression. Confirmatory and exploratory factor analyses were performed to test the psychometric abilities of the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the self-rated Beck Depression Inventory. A combined factor analysis was also conducted including all items of all scales. Results All three scales showed good to very good internal consistency. The HAMD-17 had four factors: an "anxiety" factor, a "depression" factor, an "insomnia" factor, and a "somatic" factor. The MADRS also had four factors: a “sadness” factor, a neurovegetative factor, a “detachment” factor and a “negative thoughts” factor, while the BDI had three factors: a "negative attitude towards self" factor, a "performance impairment" factor, and a "somatic" factor. The combined factor analysis suggested that self-ratings might reflect a distinct illness dimension within major depression. Conclusions The factors obtained in this study are comparable to those found in previous research. Self and clinician ratings are complementary and not redundant, highlighting the importance of using multiple measures to quantify depression.

Abstract Background Climate change is one of the greatest threats to health that societies face and can adversely affect mental health. Given the current lack of a European consensus paper on the interplay between climate change and mental health, we signal a need for a pan-European position paper about this topic, written by stakeholders working in mental health care. Methods On behalf of the European Psychiatric Association (EPA), we give recommendations to make mental health care, research, and education more sustainable based on a narrative review of the literature. Results Examples of sustainable mental healthcare comprise preventive strategies, interdisciplinary collaborations, evidence-based patient care, addressing social determinants of mental health, maintaining health services during extreme weather events, optimising use of resources, and sustainable facility management. In mental health research, sustainable strategies include investigating the impact of climate change on mental health, promoting research on climate change interventions, strengthening the evidence base for mental health-care recommendations, evaluating the allocation of research funding, and establishing evidence-based definitions and clinical approaches for emerging issues such as ‘eco-distress’. Regarding mental health education, planetary health, which refers to human health and how it is intertwined with ecosystems, may be integrated into educational courses. Conclusions The EPA is committed to combat climate change as the latter poses a threat to the future of mental health care. The current EPA position paper on climate change and mental health may be of interest to a diverse readership of stakeholders, including clinicians, researchers, educators, patients, and policymakers.

Abstract Background Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians’ treatment choices for post-traumatic stress disorder (PTSD). Methods The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). Results About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct “profiles” of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. Conclusions Clinicians’ decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

IntroductionBased on two diagnostic accuracy studies in high-prevalence settings, two distinctly different combinations of cut-off values have been recommended to identify persons at risk for somatic symptom disorder (SSD) with the combination of the Patient-Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Disorder—B Criteria Scale (SSD-12). We investigated whether the reported sensitivity and specificity of both recommended cut-off combinations are transferable to primary care.MethodsIn a cross-sectional study, 420 unselected adult primary care patients completed PHQ-15 and SSD-12. Patients scoring ≥9 and ≥ 23 (recommended cut-off combination #1) or ≥ 8 and ≥ 13 (recommended cut-off combination #2) were considered test-positive for SSD, respectively. To assess the validity of the reported sensitivity and specificity in different low- to high-prevalence settings, we compared correspondingly expected proportions of test positives to the proportion observed in our sample.ResultsBased on combination #1, 38 participants (9%) were found to be test positive, far fewer than expected, based on the reported values for sensitivity and specificity (expected minimum frequency 30% with a true prevalence ≥1%). This can only be explained by a lower sensitivity and higher specificity in primary care. For combination #2, 98 participants (23%) were test positive, a finding consistent with a true prevalence of SSD of 15% or lower.DiscussionOur analyzes strongly suggest that the sensitivity and specificity estimates reported for combination #1 are not applicable to unselected primary care patients and that the cut-off for the SSD (≥23) is too strict. Cut-off combination #2 seems more applicable but still needs to be tested in studies that compare screening findings by questionnaires with validated diagnostic interviews as reference standards in primary care populations.

The digitalisation of mental health care is expected to improve the accessibility and quality of specialised treatment services and introduce innovative methods to study, assess, and monitor mental health disorders. In this narrative review and practical recommendation of the European Psychiatric Association (EPA), we aim to help healthcare providers and policymakers to navigate this rapidly evolving field. We provide an overview of the current scientific and implementation status across two major domains of digitalisation: i) digital mental health interventions and ii) digital phenotyping, discuss the potential of each domain to improve the accessibility and outcomes of mental health services, and highlight current challenges faced by researchers, clinicians, and service users. Furthermore, we make several recommendations meant to foster the widespread adoption of evidence-based digital solutions for mental health care in the member states of the EPA. To realise the vision of a digitalised, patient-centred, and data-driven mental health ecosystem, a number of implementation challenges must be considered and addressed, spanning from human, technical, ethical–legal, and economic barriers. The list of priority areas and action points our expert panel has identified could serve as a playbook for this process.

The sudden appearance and devastating effects of the COVID-19 pandemic resulted in the need for multiple adaptive changes in societies, business operations and healthcare systems across the world. This review describes the development and increased use of digital technologies such as chat bots, electronic diaries, online questionnaires and even video gameplay to maintain effective treatment standards for individuals with mental health conditions such as depression, anxiety and post-traumatic stress syndrome. We describe how these approaches have been applied to help meet the challenges of the pandemic in delivering mental healthcare solutions. The main focus of this narrative review is on describing how these digital platforms have been used in diagnostics, patient monitoring and as a treatment option for the general public, as well as for frontline medical staff suffering with mental health issues.

Abstract Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.

Objective: Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play an important role in BPD pathology. The present study aimed to deepen the knowledge about the processes behind shame and guilt in patients with BPD. Methods: Twenty patients with BPD and twenty healthy controls (HCs) took part in an experiment that induced shame and guilt by imagining scenarios during scanning using functional brain imaging. Participants also filled out self-report questionnaires and took part in diagnostic interviews. Results: BPD patients reported more proneness to guilt but not to shame than the HCs. There was no difference in the self-reported intensity rating of experimentally induced emotions between the groups. Between-group contrast of neural signals in the shame condition revealed a stronger activation of cingulate and fusiform gyrus for the BPD patients compared to the controls, and a more pronounced activation in the lingual gyrus and cuneus for the HCs. In the guilt condition, activation in the caudate nucleus, the fusiform gyrus, and the posterior cingulate cortex was stronger in BPD patients, while HC showed stronger activations in cuneus, lingual gyrus, and fronto-temporal regions. Conclusions: Differences in the neuro-functional processes between BPD patients and HC were found, even though the two groups did not differ in their self-report of subjective proneness to guilt and emotional intensity of shame and guilt during the experiment. While the HCs may be engaged more by the emotional scenarios themselves, the BPD patients may be more occupied with cognitive regulatory and self-referential processing.

Abstract The “Patient Assessment of Chronic Illness Care” (PACIC) is a tool for evaluating outpatient health service for patients with chronic diseases. Our aim was to analyze the association between PACIC scores of primary care patients with depression and patients’ or patients’ general practitioners’ (GPs) characteristics. In a data set including depressive primary care patients (N = 280) the association of patient characteristics (sex, age, depressive symptom severity, suicidal ideation) with PACIC scores were assessed by linear regression models. The association between GPs’ characteristics (type, location of practice; age, qualification of practitioner) and PACIC scores was assessed by linear mixed models with individual practices as random effects. Patient Health Questionnaire (PHQ-9) scores at 12 months follow up and changes in PHQ-9 scores from baseline to follow up were significantly positive associated with higher PACIC scores (beta = 0.67, 95%-CI [0.02, 1.34]). PACIC scores were not associated with patients’ sex (p = 0.473) or age (p = 0.531). GP’s age was negatively associated with PACIC scores (p = 0.03). In conclusion, in patients with depression, the PACIC is independent from patients’ and GPs’ characteristics. The PACIC may be appropriate to assess patient-perspective on depression services in primary care.

Abstract Parkinson´s disease (PD) pathology progresses throughout the nervous system. Whereas motor symptoms are always present, there is a high variability in the prevalence of non-motor symptoms. It has been postulated that the progression of the pathology is based on a prion-like disease mechanism partly due to the seeding effect of endocytosed-alpha-synuclein (ASYN) on the endogenous ASYN. Here, we analyzed the role of endogenous ASYN in the progression of PD-like pathology in vivo and in vitro and compared the effect of endocytosed-ASYN as well as paraquat and rotenone on primary enteric, dopaminergic and cortical neurons from wild-type and ASYN-KO mice. Our results show that, in vivo, pathology progression did not occur in the absence of endogenous ASYN. Remarkably, the damage caused by endocytosed-ASYN, rotenone or paraquat was independent from endogenous ASYN and related to the alteration of the host´s mitochondrial membrane potential. Dopaminergic neurons were very sensitive to these noxae compared to other neuronal subtypes. These results suggest that ASYN-mitochondrial interactions play a major role in initiating the pathological process in the host neuron and endogenous ASYN is essential for the transsynaptical transmission of the pathology. Our results also suggest that protecting mitochondrial function is a valid primary therapeutic target.

Abstract Background The interdisciplinary research training group (POKAL) aims to improve care for patients with depression and multimorbidity in primary care. POKAL includes nine projects within the framework of the Chronic Care Model (CCM). In addition, POKAL will train young (mental) health professionals in research competences within primary care settings. POKAL will address specific challenges in diagnosis (reliability of diagnosis, ignoring suicidal risks), in treatment (insufficient patient involvement, highly fragmented care and inappropriate long-time anti-depressive medication) and in implementation of innovations (insufficient guideline adherence, use of irrelevant patient outcomes, ignoring relevant context factors) in primary depression care. Methods In 2021 POKAL started with a first group of 16 trainees in general practice (GPs), pharmacy, psychology, public health, informatics, etc. The program is scheduled for at least 6 years, so a second group of trainees starting in 2024 will also have three years of research-time. Experienced principal investigators (PIs) supervise all trainees in their specific projects. All projects refer to the CCM and focus on the diagnostic, therapeutic, and implementation challenges. Results The first cohort of the POKAL research training group will develop and test new depression-specific diagnostics (hermeneutical strategies, predicting models, screening for suicidal ideation), treatment (primary-care based psycho-education, modulating factors in depression monitoring, strategies of de-prescribing) and implementation in primary care (guideline implementation, use of patient-assessed data, identification of relevant context factors). Based on those results the second cohort of trainees and their PIs will run two major trials to proof innovations in primary care-based a) diagnostics and b) treatment for depression. Conclusion The research and training programme POKAL aims to provide appropriate approaches for depression diagnosis and treatment in primary care.

Individuals with Autism Spectrum Disorder (ASD) are thought to under-rely on prior knowledge in perceptual decision-making. This study examined whether this applies to decisions of attention allocation, of relevance for 'predictive-coding' accounts of ASD. In a visual search task, a salient but task-irrelevant distractor appeared with higher probability in one display half. Individuals with ASD learned to avoid 'attentional capture' by distractors in the probable region as effectively as control participants--indicating typical priors for deploying attention. However, capture by a 'surprising' distractor at an unlikely location led to greatly slowed identification of a subsequent target at that location--indicating that individuals with ASD attempt to control surprise (unexpected attentional capture) by over-regulating parameters in post-selective decision-making.

Abstract The diagnostic criteria for schizophrenia (SCZ) and bipolar disorder (BD) are based on clinical assessments of symptoms. In this pilot study, we applied high-throughput antibody-based protein profiling to serum samples of healthy controls and individuals with SCZ and BD with the aim of identifying differentially expressed proteins in these disorders. Moreover, we explored the influence of polygenic burden for SCZ and BD on the serum levels of these proteins. Serum samples from 113 individuals with SCZ and 125 with BD from the PsyCourse Study and from 44 healthy controls were analyzed by using a set of 155 antibodies in an antibody-based assay targeting a selected panel of 95 proteins. For the cases, genotyping and imputation were conducted for DNA samples and SCZ and BD polygenic risk scores (PRS) were calculated. Univariate linear and logistic models were used for association analyses. The comparison between SCZ and BD revealed two serum proteins that were significantly elevated in BD after multiple testing adjustment: “complement C9” and “Interleukin 1 Receptor Accessory Protein”. Moreover, the first principal component of variance in the proteomics dataset differed significantly between SCZ and BD. After multiple testing correction, SCZ-PRS, BD-PRS, and SCZ-vs-BD–PRS were not significantly associated with the levels of the individual proteins or the values of the proteome principal components indicating no detectable genetic effects. Overall, our findings contribute to the evidence suggesting that the analysis of circulating proteins could lead to the identification of distinctive biomarkers for SCZ and BD. Our investigation warrants replication in large-scale studies to confirm these findings.

Abstract Aims Transcranial direct current stimulation (tDCS) applied to the prefrontal cortex has been frequently used to elicit behavioral changes in patients with schizophrenia. However, the interaction between prefrontal tDCS and electrophysiological changes remains largely uncharted. The present study aimed to investigate cortical electrophysiological changes induced by tDCS in frontal areas by means of repeated electroencephalography (EEG) in patients with schizophrenia. Methods In total, 20 patients with schizophrenia received 13 minutes of anodal tDCS (1 mA) applied to the left dorsolateral prefrontal cortex (DLPFC). Repeated resting EEG was recorded before (once) and following (at five follow‐up time‐bins) tDCS to trace post‐tDCS effects. We used sLORETA for source reconstruction to preserve the localization of brain signals with a low variance and to analyze frequency changes. Results We observed significant changes after the stimulation in areas highly connected with the stimulated DLPFC areas. The alpha 1 (8.5‐10.0 Hz) activity showed a highly significant, long‐lasting, increase for up to 1 hour after the stimulation in the postcentral gyrus (Brodmann area 2, 3, and 40). Significant yet unstable changes were also seen in the alpha‐2 frequency band precentral at 10 minutes, in the beta‐1 frequency band occipital at 20 minutes, and in the beta‐3 frequency band temporal at 40 minutes. Conclusion We were able to show that anodal tDCS can induce stable EEG changes in patients with schizophrenia. The results underline the potential of tDCS to induce long‐lasting neurophysiological changes in patients with schizophrenia showing the possibility to induce brain excitability changes in this population.

Abstract Hippocampal formation (HF) volume loss is a well-established finding in schizophrenia, with select subfields, such as the cornu ammonis and dentate gyrus, being particularly vulnerable. These morphologic alterations are related to functional abnormalities and cognitive deficits, which are at the core of the insufficient recovery frequently seen in this illness. To counteract HF volume decline, exercise to improve aerobic fitness is considered as a promising intervention. However, the effects of aerobic fitness levels on HF subfields are not yet established in individuals with schizophrenia. Therefore, our study investigated potential associations between aerobic fitness and HF subfield structure, functional connectivity, and related cognitive impact in a multiparametric research design. In this cross-sectional study, 53 participants diagnosed with schizophrenia (33 men, 20 women; mean [SD] age, 37.4 [11.8] years) underwent brain structural and functional magnetic resonance imaging and assessments of aerobic fitness and verbal memory. Multivariate multiple linear regressions were performed to determine whether aerobic fitness was associated with HF subfield volumes and functional connections. In addition, we explored whether identified associations mediated verbal memory functioning. Significant positive associations between aerobic fitness levels and volumes were demonstrated for most HF subfields, with the strongest associations for the cornu ammonis, dentate gyrus, and subiculum. No significant associations were found for HF functional connectivity or mediation effects on verbal memory. Aerobic fitness may mitigate HF volume loss, especially in the subfields most affected in schizophrenia. This finding should be further investigated in longitudinal studies. Clinical Trials Registration: The study on which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Abstract Background Despite high acceptance rates in the field, the implementation of the 2019 published German evidence and consensus-based S3 guideline is unsatisfactory. This study aims to assess the superiority of an adaptive online version with a better visualization of the recommendations in terms of guideline conformity, application of shared decision making, and digital health expertise compared to the classic pdf print version of the guideline. Methods The study is a multicenter, controlled, cluster-randomized trial with two arms: one arm investigating the implementation of the German schizophrenia guideline in form of a digital format (intervention group using the evidence ecosystem MAGICapp), the other arm in form of the classic print pdf version (control group). Physicians and psychologists working in specialized hospitals will be included in the study. The guideline-knowledge before and after the intervention is defined as primary outcome measure. Secondary endpoints include digital health expertise and application of shared decision making. Discussion This is the first study evaluating if an adaptive-digital version of the schizophrenia guideline is superior to the classic pdf print version. Therefore, the guideline is digitally prepared in the evidence-ecosystem MAGICapp, which covers the whole process of the development of a living guideline. We intend to use the results of the cluster-randomized trial for developing the German S3 guideline for schizophrenia in form of a living guideline in future. Trial registration The study is registered (10 May 2022) in the German Clinical Trials Register (DRKS) and the WHO International Clinical Trials Registry Platform (ICTRP) under registration number DRKS00028895 .

IntroductionThe Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome.MethodA sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses.ResultWe extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups.ConclusionPsychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being related to a stricter rating of APS/BIPS and cultural influences, in particular, higher schizotypy reported in North-America. The various associations of some APS/BIPS contents with country, age, comorbidities, and functioning might moderate their clinical severity and, consequently, the related risk for psychosis and/or persistent functional disability.

Background Refugees and asylum seekers (RAS) in Germany need tailored and resource-oriented mental healthcare interventions. Aims To evaluate the cost-effectiveness of group psychotherapy for RAS with moderate depressive symptoms. Method This is a post hoc cost-effectiveness analysis of Empowerment group psychotherapy that was embedded in a stratified stepped and collaborative care model (SCCM) from the multicentre randomised controlled MEHIRA trial. One hundred and forty-nine participants were randomly assigned to SCCM or treatment as usual (TAU) and underwent Empowerment (i.e. level 3 of the SCCM for adults) or TAU. Effects were measured with the nine-item Patient Health Questionnaire (PHQ-9) and quality adjusted life-years (QALY) post-intervention. Health service and intervention costs were measured. Incremental cost-effectiveness ratios (ICER) were estimated and net monetary benefit (NMB) regressions with 95% confidence intervals were performed. Cost-effectiveness was ascertained for different values of willingness to pay (WTP) using cost-effectiveness acceptability curves for probable scenarios. Trial registration number: NCT03109028 on ClinicalTrials.gov. Results Health service use costs were significantly lower for Empowerment than TAU after 1 year. Intervention costs were on average €409.6. Empowerment led to a significant change in PHQ-9 scores but not QALY. Bootstrapped mean ICER indicated cost-effectiveness according to PHQ-9 and varied considerably for QALY in the base case. NMB for a unit reduction in PHQ-9 score at WTP of €0 was €354.3 (€978.5 to −€269.9). Results were confirmed for different scenarios and varying WTP thresholds. Conclusions The Empowerment intervention was cost-effective in refugees with moderate depressive symptoms regarding the clinical outcome and led to a reduction in direct healthcare consumption. Concerning QALYs, there was a lack of confidence that Empowerment differed from TAU.

BackgroundTreatment guidelines for psychosis recommend offering psychotherapy already in the acute illness phase. However, there is a lack of available interventions adapted to the specific needs and key change mechanisms of inpatients experiencing severe symptoms and crisis. In this article we outline the scientific development process of a needs-oriented and mechanism-based group intervention for acute psychiatric inpatients with psychosis (MEBASp).MethodsTo guide our intervention design, we used Intervention Mapping (IM), a six-step framework for developing evidence-based health interventions that consisted of an extensive literature review, an in-depth problem definition and needs analysis, the modeling of change mechanisms and outcomes and the production of an intervention prototype.ResultsOur low-threshold modularized group intervention consists of nine stand-alone sessions (two per week) within three modules and targets different aspects of metacognitive and social change mechanisms. Module I and II aim to reduce acute symptoms by fostering cognitive insight, Module III focuses on reducing distress via cognitive defusion. Therapy contents are adapted from existing metacognitive treatments such as the Metacognitive Training and presented in a destigmatizing, simply understandable and experience-oriented way.ConclusionMEBASp is currently evaluated in a single-arm feasibility trial. Using a systematic and rigorous development methodology and providing a detailed description of the development steps demonstrated to be invaluable in improving the intervention’s scientific foundation, validity, and replicability for similar research.

As core symptoms of schizophrenia, cognitive deficits contribute substantially to poor outcomes. Early life stress (ELS) can negatively affect cognition in patients with schizophrenia and healthy controls, but the exact nature of the mediating factors is unclear. Therefore, we investigated how ELS, education, and symptom burden are related to cognitive performance.The sample comprised 215 patients with schizophrenia (age, 42.9 ± 12.0 years; 66.0 % male) and 197 healthy controls (age, 38.5 ± 16.4 years; 39.3 % male) from the PsyCourse Study. ELS was assessed with the Childhood Trauma Screener (CTS). We used analyses of covariance and correlation analyses to investigate the association of total ELS load and ELS subtypes with cognitive performance.ELS was reported by 52.1 % of patients and 24.9 % of controls. Independent of ELS, cognitive performance on neuropsychological tests was lower in patients than controls (p

Der 21. Deutsche Kongress für Versorgungsforschung, der vom 5. bis 7. Oktober 2022 in Potsdam stattfinden wird, steht unter dem Motto „Versorgungsforschung – Nutzen für die klinische Praxis – Potentiale und Perspektiven“. Es solle, so schreibt Prof. Dr. med. Peter Falkai in seiner Begrüßung als Kongresspräsident, zuvörderst diskutiert werden, „welchen Nutzen die Versorgungsforschung für die klinische Realität und somit konkret für Patient:innen bereithält“. Was Falkai, hauptberuflich Direktor der Psychiatrischen Klinik des LMU Klinikums München, darunter versteht, erklärt er im Titelinterview von „Monitor Versorgungsforschung“. Seine wichtigsten Hauptforderungen: Vernetzung, Replizierbarkeit, Qualitätsstandards und -kontrolle sowie „Back Translation“.

Abstract Childhood maltreatment (CM) has been associated with adverse psychosocial outcomes during the pandemic, but the underlying mechanisms are unclear. In a prospective online study using baseline and 10-week follow-up data of 391 German participants, we applied multiple mediation analyses to test to what extent COVID-19 perceived stressors mediate the association between CM and later adverse psychosocial outcomes compared to established mediators of rumination and insecure attachment. We also explored the relative importance of different COVID-19 related stressors in predicting adverse psychological trajectories using elastic net regression. Results showed that CM was longitudinally associated with all adverse psychosocial outcome. COVID-19 perceived stressors, rumination, and insecure attachment mediated this relationship and full mediation was observed for the outcomes anxiety, stress and psychological well-being. COVID-19-related concerns about the future was most strongly and consistently associated with adverse psychosocial functioning. These findings provide preliminary evidence that COVID-19 perceived stressors, in particular concerns about the future, may be a key mechanism underlying the development of adverse psychosocial outcomes in individuals with a CM history. Thus, COVID-19 perceived stressors may require a higher priority for prevention and treatment efforts in vulnerable groups. Our results warrant replication in more representative cross-cultural samples.

IntroductionTreatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis.MethodsIn line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP) study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the study includes in vitro investigations on human-induced pluripotent stem cells, which are available from a subset of participants.ResultsHere, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and study objectives.DiscussionThe identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat.

Background Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood–brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated. Aims To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention. Method We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest. Results Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments. Conclusions The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed.