Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.

Predictors of adherence to exercise interventions in people with schizophrenia.

Exercise interventions are nowadays considered as effective add-on treatments in people with schizophrenia but are usually associated with high dropout rates. Therefore, the present study investigated potential predictors of adherence from a large multicenter study, encompassing two types of exercise training, conducted over a 6-month period with individuals with schizophrenia. First, we examined the role of multiple participants' characteristics, including levels of functioning, symptom severity, cognitive performance, quality of life, and physical fitness. Second, we used K-means clustering to identify clinical subgroups of participants that potentially exhibited superior adherence. Last, we explored if adherence could be predicted on the individual level using Random Forest, Logistic Regression, and Ridge Regression. We found that individuals with higher levels of functioning at baseline were more likely to adhere to the exercise interventions, while other factors such as symptom severity, cognitive performance, quality of life or physical fitness seemed to be less influential. Accordingly, the high-functioning group with low symptoms exhibited a greater likelihood of adhering to the interventions compared to the severely ill group. Despite incorporating various algorithms, it was not possible to predict adherence at the individual level. These findings add to the understanding of the factors that influence adherence to exercise interventions. They underscore the predictive importance of daily life functioning while indicating a lack of association between symptom severity and adherence. Future research should focus on developing targeted strategies to improve adherence, particularly for people with schizophrenia who suffer from impairments in daily functioning.Clinical trials registration The study of this manuscript which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804.

Assessing the impact of sex on high-frequency repetitive transcranial magnetic stimulation´s clinical response in schizophrenia - results from a secondary analysis.

Background: The evidence for repetitive transcranial magnetic stimulation (rTMS) to treat negative symptoms in schizophrenia (SCZ) is increasing, although variable response rates remain a challenge. Subject´s sex critically influences rTMS´ treatment outcomes. Females with major depressive disorder are more likely to respond to rTMS, while SCZ data is scarce.Methods: Using data from the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial we assessed the impact of sex on rTMS´ clinical response rate from screening up to 105 days after intervention among SCZ patients. The impact of resting motor threshold (RMT) on response rates was also assessed.Results: 157 patients received either active or sham rTMS treatment. No significant group differences were observed. Linear mixed model showed no effects on response rates (all p > 0.519). Apart from a significant sex*time interaction for the positive subscale of the positive and negative syndrome scale (PANSS) scores (p = 0.032), no other significant effects of sex on continuous PANSS scores were observed. RMT had no effect on response rate.Conclusion: In the largest rTMS trial on the treatment of SCZ negative symptoms we did not observe any significant effect of sex on treatment outcomes. Better assessments of sex-related differences could improve treatment individualization.

Characterizing cognitive subtypes in schizophrenia using cortical curvature.

Cognitive deficits are a core symptom of schizophrenia, but research on their neural underpinnings has been challenged by the heterogeneity in deficits' severity among patients. Here, we address this issue by combining logistic regression and random forest to classify two neuropsychological profiles of patients with high (HighCog) and low (LowCog) cognitive performance in two independent samples. We based our analysis on the cortical features grey matter volume (VOL), cortical thickness (CT), and mean curvature (MC) of N = 57 patients (discovery sample) and validated the classification in an independent sample (N = 52). We investigated which cortical feature would yield the best classification results and expected that the 10 most important features would include frontal and temporal brain regions. The model based on MC had the best performance with area under the curve (AUC) values of 76% and 73%, and identified fronto-temporal and occipital brain regions as the most important features for the classification. Moreover, subsequent comparison analyses could reveal significant differences in MC of single brain regions between the two cognitive profiles. The present study suggests MC as a promising neuroanatomical parameter for characterizing schizophrenia cognitive subtypes.

[Management of treatment resistance-Treatment-resistant schizophrenia]. / Management von Therapieresistenzen ­ therapieresistente Schizophrenie.

Despite a very high prevalence and substantial impairments among affected individuals, treatment-resistant schizophrenia (TRS) has not been sufficiently researched in clinical research in the field of psychiatric disorders and the pathophysiology is still poorly understood. A better clinical and pathophysiological understanding of this heterogeneous and severely affected population of people with persistent symptoms in different domains is necessary in order not only to be able to intervene early but also to develop novel therapeutic strategies or individualized treatment approaches. This review article presents the state of the art criteria of the pharmacological TRS, neurobiological disease models and predictive factors for TRS as well as the phenomenon of pseudo-treatment resistance and the clinical management of TRS. In the future, not only the use of operationalized criteria and definitions of TRS in longitudinal studies and randomized-controlled trials (RCTs) are paramount, but also the observation of trajectories with the integration of multimodal longitudinal phenotyping and the longitudinal collection of clinical routine data in academic research, which will be possible in the newly created German Center for Mental Health (DZPG).

Vaccination and clozapine use: a systematic review and an analysis of the VAERS database.

In the context of COVID-19 concerns related to the potential interactions between clozapine and vaccination arose. With the ultimate goal of deriving recommendations for clinical practice, we systematically reviewed the current evidence regarding altered vaccine effectiveness in clozapine-treated patients and safety aspects of vaccination, such as haematological changes and the impact of vaccines on clozapine blood levels, in clozapine-treated patients. A systematic PRISMA-conform literature search of four databases (PubMed, PsycINFO, EMBASE and Cochrane Library) complemented by a case-by-case analysis of the Vaccine Adverse Event Reporting System (VAERS) database was performed. We then systematically appraised the joint evidence and tried to derive recommendations for clinical practice. 14 records were included in this analysis. These records consisted of 5 original articles and 9 case reports. Among the original articles, two studies provided data on the association between clozapine use and antibody responses to vaccination, both indicating that clozapine use in schizophrenia may be associated with reduced levels of immunoglobulins. Additionally, three studies examined vaccine safety in clozapine-treated patients, with no clinically significant adverse effects directly attributable to the interplay between vaccinations and clozapine. VAERS Analysis encompassed 137 reports and showed no consistent evidence of an increased risk for clozapine blood level increases or adverse events. We found no evidence indicating that clozapine impairs the effectiveness of vaccines. Moreover, no serious safety concerns seem to apply when patients on clozapine are receiving vaccines. However, it is crucial to acknowledge that data on the interaction between clozapine and vaccines remain limited.

Illusory generalizability of clinical prediction models.

It is widely hoped that statistical models can improve decision-making related to medical treatments. Because of the cost and scarcity of medical outcomes data, this hope is typically based on investigators observing a model's success in one or two datasets or clinical contexts. We scrutinized this optimism by examining how well a machine learning model performed across several independent clinical trials of antipsychotic medication for schizophrenia. Models predicted patient outcomes with high accuracy within the trial in which the model was developed but performed no better than chance when applied out-of-sample. Pooling data across trials to predict outcomes in the trial left out did not improve predictions. These results suggest that models predicting treatment outcomes in schizophrenia are highly context-dependent and may have limited generalizability.

Polygenic risk for schizophrenia converges on alternative polyadenylation as molecular mechanism underlying synaptic impairment.

Schizophrenia (SCZ) is a genetically heterogenous psychiatric disorder of highly polygenic nature. Correlative evidence from genetic studies indicate that the aggregated effects of distinct genetic risk factor combinations found in each patient converge onto common molecular mechanisms. To prove this on a functional level, we employed a reductionistic cellular model system for polygenic risk by differentiating induced pluripotent stem cells (iPSCs) from 104 individuals with high polygenic risk load and controls into cortical glutamatergic neurons (iNs). Multi-omics profiling identified widespread differences in alternative polyadenylation (APA) in the 3' untranslated region of many synaptic transcripts between iNs from SCZ patients and healthy donors. On the cellular level, 3'APA was associated with a reduction in synaptic density of iNs. Importantly, differential APA was largely conserved between postmortem human prefrontal cortex from SCZ patients and healthy donors, and strongly enriched for transcripts related to synapse biology. 3'APA was highly correlated with SCZ polygenic risk and affected genes were significantly enriched for SCZ associated common genetic variation. Integrative functional genomic analysis identified the RNA binding protein and SCZ GWAS risk gene PTBP2 as a critical trans-acting factor mediating 3'APA of synaptic genes in SCZ subjects. Functional characterization of PTBP2 in iNs confirmed its key role in 3'APA of synaptic transcripts and regulation of synapse density. Jointly, our findings show that the aggregated effects of polygenic risk converge on 3'APA as one common molecular mechanism that underlies synaptic impairments in SCZ.

Culturally sensitive stepped care for adolescent refugees: efficacy and cost-utility of a multicentric randomized controlled trial.

Adolescent refugees and asylum seekers (ARAS) are highly vulnerable to mental health problems. Stepped care models (SCM) and culturally sensitive therapies offer promising treatment approaches to effectively provide necessary medical and psychological support. To our knowledge, we were the first to investigate whether a culturally sensitive SCM will reduce symptoms of depression and PTSD in ARAS more effectively and efficiently than treatment as usual (TAU). We conducted a multicentric, randomized, controlled and rater-blinded trial across Germany with ARAS between the ages of 14 to 21 years. Participants (N = 158) were stratified by their level of depressive symptom severity and then equally randomized to either SCM or TAU. Depending on their severity level, SCM participants were allocated to tailored interventions. Symptom changes were assessed for depression (PHQ) and PTSD (CATS) at four time points, with the primary end point at post-intervention after 12 weeks. Based on an intention-to-treat sample, we used a linear mixed model approach for the main statistical analyses. Further evaluations included cost-utility analyses, sensitivity analyses, follow-up-analyses, response and remission rates and subgroup analysis. We found a significant reduction of PHQ (d = 0.52) and CATS (d = 0.27) scores in both groups. However, there was no significant difference between SCM and TAU. Cost-utility analyses indicated that SCM generated greater cost-utility when measured as quality-adjusted life years compared to TAU. Subgroup analysis revealed different effects for the SCM interventions depending on the outcome measure. Although culturally sensitive, SCMs did not prove to be more effective in symptom change and represent a more cost-effective treatment alternative for mentally burdened ARAS. Our research contributes to the optimization of clinical productivity and the improvement of therapeutic care for ARAS. Disorder-specific interventions should be further investigated.

Polygenetic risk scores and phenotypic constellations of obsessive-compulsive disorder in clozapine-treated schizophrenia.

Obsessive-compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive-compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Participants were divided into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS analyses were performed to evaluate the association between either phenotypic OCD or OCS severity and genotype-predicted predisposition for OCD, SCZ, cross-disorder, and CLZ/norclozapine (NorCLZ) ratio, CLZ metabolism and NorCLZ metabolism. OCS and OCD were frequent comorbidities in our sample of CLZ-treated SCZ individuals, with a prevalence of 39.6% and 27.5%, respectively. Furthermore, the Y-BOCS total score correlated positively with the duration of CLZ treatment in years (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). A significant correlation was found between OCD occurrence and PRS for CLZ metabolism. We found no correlation between OCS severity and PRS for CLZ metabolism. We found no correlation for either OCD or OCS and PRS for OCD, cross-disorder, SCZ, CLZ/NorCLZ ratio or NorCLZ metabolism. Our study was able to replicate previous findings on clinical characteristics of CLZ-treated SCZ individuals. OCS is a frequent comorbidity in this cohort and is correlated with CLZ treatment duration in years and PANSS general psychopathology subscale score. We found a correlation between OCD and PRS for CLZ metabolism, which should be interpreted as incidental for now. Future research is necessary to replicate significant findings and to assess possible genetic predisposition of CLZ-treated individuals with SCZ to OCS/OCD. Limitations attributed to the small sample size or the inclusion of subjects on co-medication must be considered. If the association between OCD and PRS for CLZ metabolism can be replicated, it should be further evaluated if CYP1A2 alteration, respectively lower CLZ plasma level, is relevant for OCD development.

Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis.

BACKGROUND: There is no consensus on defining relapse in schizophrenia, and scale-derived criteria with unclear clinical relevance are widely used. We aimed to develop an evidence-based scale-derived set of criteria to define relapse in patients with schizophrenia or schizoaffective disorder. METHODS: We searched the Yale University Open Data Access (YODA) for randomised controlled trials (RCTs) in clinically stable adults with schizophrenia or schizoaffective disorder, and obtained individual participant data on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity (CGI-S), Personal and Social Performance (PSP), and Social and Occupational Functioning Assessment Scale (SOFAS). Our main outcomes were PANSS-derived criteria based on worsening in PANSS total score. We examined their relevance using equipercentile linking with CGI-S and functioning scales, and their test-performance in defining relapse with diagnostic test accuracy meta-analysis against CGI-S worsening (≥1-point increase together with a score ≥4 points) and psychiatric hospitalisation. FINDINGS: Based on data from seven RCTs (2354 participants; 1348 men [57·3%] and 1006 women [42·7%], mean age of 39·5 years [SD 12·0, range 17-89]; 303 Asian [12.9%], 255 Black [10.8%], 1665 White [70.7%], and other or unspecified 131 [5.6%]), an increase of 12 points or more in PANSS total (range 30-210 points) corresponded to clinically important deterioration in global severity of illness (≥1 point increase in CGI-S, range 1-7) and functioning (≥10 points decline in PSP or SOFAS, range 1-100). The interpretation of percentage changes varied importantly across different baseline scores. An increase of 12 points or more in PANSS total had good sensitivity and specificity using CGI-S as reference standard (sensitivity 82·1% [95% CI 77·1-86·4], specificity 86·9% [82·9-90·3]), as well as good sensitivity but lower specificity compared to hospitalisation (sensitivity 81·7% [74·1-87·7], specificity 69·2% [60·5-76·9]). Requiring either an increase in PANSS total or in specific items for positive and disorganization symptoms further improved test-performance. Cutoffs for situations where high sensitivity or specificity is needed are presented. INTERPRETATION: An increase of either 12 points or more in the PANSS total score, or worsening of specific positive and disorganisation symptom items could be a reasonable evidence-based definition of relapse in schizophrenia, potentially linking symptoms used to define remission and relapse. Percentage changes should not be used to define relapse because their interpretation depends on baseline scores. FUNDING: German Research Foundation (grant number: 428509362).

Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia-Data From a Multicenter Randomized-Controlled Study.

BACKGROUND AND HYPOTHESIS: Aerobic exercise interventions in people with schizophrenia have been demonstrated to improve clinical outcomes, but findings regarding the underlying neural mechanisms are limited and mainly focus on the hippocampal formation. Therefore, we conducted a global exploratory analysis of structural and functional neural adaptations after exercise and explored their clinical implications. STUDY DESIGN: In this randomized controlled trial, structural and functional MRI data were available for 91 patients with schizophrenia who performed either aerobic exercise on a bicycle ergometer or underwent a flexibility, strengthening, and balance training as control group. We analyzed clinical and neuroimaging data before and after 6 months of regular exercise. Bayesian linear mixed models and Bayesian logistic regressions were calculated to evaluate effects of exercise on multiple neural outcomes and their potential clinical relevance. STUDY RESULTS: Our results indicated that aerobic exercise in people with schizophrenia led to structural and functional adaptations mainly within the default-mode network, the cortico-striato-pallido-thalamo-cortical loop, and the cerebello-thalamo-cortical pathway. We further observed that volume increases in the right posterior cingulate gyrus as a central node of the default-mode network were linked to improvements in disorder severity. CONCLUSIONS: These exploratory findings suggest a positive impact of aerobic exercise on 3 cerebral networks that are involved in the pathophysiology of schizophrenia. CLINICAL TRIALS REGISTRATION: The underlying study of this manuscript was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Association of Four Medication Classes and Non-suicidal Self-injury in Adolescents with Affective Disorders - A Retrospective Chart Review.

BACKGROUND: Non-suicidal self-injury (NSSI) behaviour is frequently observed in children and adolescents with psychiatric conditions. Affected individuals are regularly treated with psychotropic drugs, although the impact of these agents on NSSI behaviour remains elusive. METHODS: We performed a retrospective chart review from clinical routine data in a large cohort (N=1140) of adolescent inpatients with primary affective and non-affective psychiatric disorders according to ICD-10 (mean age=15.3±1.3 years; 72.6% female). Four separate mixed regression models compared the frequency of NSSI between treatment periods without any medication and four medication categories (benzodiazepines, selective serotonin reuptake inhibitors (SSRIs), high- and low-potency antipsychotics). RESULTS: In those individuals with affective disorders as the primary diagnosis, periods without medication were associated with significantly lower NSSI/day compared to all four other medication conditions (benzodiazepines p<10-8, antidepressants/SSRIs p=0.0004, high-potency antipsychotics p=0.0009, low-potency antipsychotics p<10 -4). In individuals with a primary diagnosis other than an affective disorder, NSSI was significantly lower during the period without medication compared to the treatment periods with benzodiazepines (p=0.005) and antidepressants/SSRIs (p=0.01). However, NSSI rates in the no-medication condition were comparable to NSSI rates under high-potency (p=0.89) and low-potency antipsychotics (p=0.53). CONCLUSIONS: The occurrence of NSSI correlates with the treatment with a psychotropic drug in children and adolescents with psychiatric disorders. Due to the retrospective design, it remains elusive to what extent psychotropic drugs might alter the frequency of NSSI in adolescents or if NSSI might indicate a transdiagnostic feature of more pronounced disease severity.

Higher Subjective Burden in Psychiatric Compared to Somatic Healthcare Workers in Germany During the first wave of the COVID-19 Pandemic.

The COVID-19 pandemic has posed unprecedented challenges for health care workers (HCWs) worldwide. While the adverse effects of the pandemic on the well-being of HCWs in general have now been established, little is known about the impact on HCWs of psychiatric hospitals (PHCWs). PHCWs are of special interest, given that they faced both an increase in infection rates among psychiatric patients as well as in mental strain of the general public due to consequences of the pandemic. The aim of the present study was to investigate how the pandemic affected PHCWs as well as possible differences between PHCWs and other health care workers (OHCWs) in Germany during the first wave of the pandemic. We conducted a country-wide anonymous online survey early during the first pandemic wave between April 15th and May 1st, 2020, to assess different aspects of subjective burden and perceived stress using 5-point Likert-scale questions. We analysed data of 1530 PHCWs and 2114 OHCWs and showed that PHCWs reported higher subjective burden and stress compared to OHCWs (p<0.001). Overall, nurses from both groups of HCWs showed higher ratings in subjective burden and stress than physicians. These higher ratings for subjective burden were even more pronounced for nurses working in psychiatric hospitals. Future research is needed to investigate the causes for PHCWs' increased stress and subjective burden, especially when taking into account the long-term effects of the pandemic, which may lead to further challenges and an ever-increasing workload, especially for PHCWs.

Challenges, unmet needs and future directions - a critical evaluation of the clinical trial landscape in schizophrenia research.

INTRODUCTION: Developing novel antipsychotic mechanisms of action and repurposing established compounds for the treatment of schizophrenia is of utmost importance to improve relevant symptom domains and to improve the risk/benefit ratio of antipsychotic compounds. Novel trial design concepts, pathophysiology-based targeted treatment approaches, or even the return to old values may improve schizophrenia outcomes in the future. AREAS COVERED: In this review of the clinical trial landscape in schizophrenia, we present an overview of the challenges and gaps in current clinical trials and elaborate on potential solutions to improve the outcomes of people with schizophrenia. EXPERT OPINION: The classic parallel group design may limit substantial advantages in drug approval or repurposing. Collaborative approaches between regulatory authorities, industry, academia, and funding agencies are needed to overcome barriers in clinical schizophrenia research to allow for meaningful outcome improvements for the patients.

Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions.

Clozapine is often underused due to concerns about adverse drug reactions (ADRs) but studies into their prevalences are inconclusive. We therefore comprehensively examined prevalences of clozapine-associated ADRs in individuals with schizophrenia and demographic and clinical factors associated with their occurrence. Data from a multi-center study (n = 698 participants) were collected. The mean number of ADRs during clozapine treatment was 4.8, with 2.4 % of participants reporting no ADRs. The most common ADRs were hypersalivation (74.6 %), weight gain (69.3 %), and increased sleep necessity (65.9 %), all of which were more common in younger participants. Participants with lower BMI prior to treatment were more likely to experience significant weight gain (>10 %). Constipation occurred more frequently with higher clozapine blood levels and doses. There were no differences in ADR prevalence rates between participants receiving clozapine monotherapy and polytherapy. These findings emphasize the high prevalence of clozapine-associated ADRs and highlight several demographic and clinical factors contributing to their occurrence. By understanding these factors, clinicians can better anticipate and manage clozapine-associated ADRs, leading to improved treatment outcomes and patient well-being.

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.

The influence of marathon running on resting-state EEG activity: a longitudinal observational study.

Physical activity (PA) has positive effects on various health aspects and neuronal functions, including neuronal plasticity. Exceeding a certain exercise frequency and duration has been associated with negative effects. Our study investigated the effects of excessive PA with a marathon run (MA) and regular PA (training and recovery phases) on electrocortical activity, as measured by electroencephalography (EEG). Thirty healthy marathon runners (26 male, 45 ± 9 yrs) were enrolled in the study. Four resting-state 32 channel EEG recordings were conducted: 12-8 weeks before MA (T-1), 14-4 days prior to MA (T0), 1-6 days after (T2), and 13-15 weeks after MA (T3). Power spectrum analyses were conducted using standardized Low-Resolution Electromagnetic Tomography (sLORETA) and included the following frequency bands: delta (1.5-6 Hz), theta (6.5-8.0 Hz), alpha1 (8.5-10 Hz), alpha2 (10.5-12.0 Hz), beta1 (12.5-18.0 Hz), beta2 (18.5-21.0 Hz), beta3 (21.5-30.0 Hz), and total power (1.5-30 Hz). Statistical nonparametric mapping showed reduced power both in the alpha-2 (log-F ratio = - 0.705, threshold log-F ratio = ± 0.685, p < 0.05) and in the delta frequency band (log-F ratio = -0.699, threshold log-F ratio = ± 0.685, p < 0.05) in frontal cortical areas after MA (T2 vs. T0). These effects diminished at long-term follow-up (T3). The results can be interpreted as correlates for subacute neuroplasticity induced by strenuous and prolonged PA. Although previous studies reported an increase in alpha frequency during and directly postexercise, the adverse observation a few days after exercise cessation suggests counterregulatory mechanisms, whose complex origin can be suspected in subcortical circuits, changes in neurotransmitter systems and modulation of affectivity.