Open Access

Background: Physical exercise has been linked to beneficial effects on brain plasticity. One potential key mechanism for this relationship is an exercise-induced increase of brain-derived neurotrophic factor (BDNF). However, the kinetics of BDNF in athletes during training phase, extreme exercise competition, and recovery period have not been investigated so far. Methods: We assessed serum BDNF concentrations in 51 marathon runners (23% female, mean age 43 years) in a longitudinal study design over a period of 6 months. Assessments were conducted during the training period before the marathon and after the marathon race during short-term (24 to 72 h) and long-term (3 months) follow-ups. Potential confounders (fitness level, sex, and platelet count) were included in subsequent linear-model analyses. Results: Linear mixed-model analyses revealed a main effect of time for BDNF concentrations over the study period (F(4,89.389) = 4.296, p = 0.003). Values decreased significantly with the lowest values at 72 h after the marathon compared to baseline (p = 0.025), a finding that was more pronounced in the larger male cohort. Conclusion: Prolonged exercise induces a significant decrease in serum BDNF concentration 72 h post-exercise. We assume that this observation is mainly driven by regenerative mechanisms and a higher muscular utilization.

The Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept “Precision in Mental Health (PriMe): Understanding, predicting, and preventing chronicity.” PriMe bundles interdisciplinary research from the Ludwig-Maximilians-University (LMU), Technical University of Munich (TUM), University of Augsburg (UniA), Helmholtz Center Munich (HMGU), and Max Planck Institute of Psychiatry (MPIP) and has a focus on schizophrenia (SZ), bipolar disorder (BPD), and major depressive disorder (MDD). PriMe takes a longitudinal perspective on these three disorders from the at-risk stage to the first-episode, relapsing, and chronic stages. These disorders pose a major health burden because in up to 50% of patients they cause untreatable residual symptoms, which lead to early social and vocational disability, comorbidities, and excess mortality. PriMe aims at reducing mortality on different levels, e.g., reducing death by psychiatric and somatic comorbidities, and will approach this goal by addressing interdisciplinary and cross-sector approaches across the lifespan. PriMe aims to add a precision medicine framework to the DZPG that will propel deeper understanding, more accurate prediction, and personalized prevention to prevent disease chronicity and mortality across mental illnesses. This framework is structured along the translational chain and will be used by PriMe to innovate the preventive and therapeutic management of SZ, BPD, and MDD from rural to urban areas and from patients in early disease stages to patients with long-term disease courses. Research will build on platforms that include one on model systems, one on the identification and validation of predictive markers, one on the development of novel multimodal treatments, one on the regulation and strengthening of the uptake and dissemination of personalized treatments, and finally one on testing of the clinical effectiveness, utility, and scalability of such personalized treatments. In accordance with the translational chain, PriMe’s expertise includes the ability to integrate understanding of bio-behavioral processes based on innovative models, to translate this knowledge into clinical practice and to promote user participation in mental health research and care.

Negative symptoms and cognitive deficits are common in individuals with schizophrenia, greatly affect their outcome, and have been associated with alterations in cerebral gray and white matter volume (GMV, WMV). In the last decade, aerobic endurance training has emerged as a promising intervention to alleviate these symptoms and improved aerobic fitness has been suggested as a key moderator variable. In the present study, we investigated, whether aerobic fitness is associated with fewer cognitive deficits and negative symptoms and with GMVs and WMVs in individuals with schizophrenia in a cross-sectional design. In the largest study to date on the implications of fitness in individuals with schizophrenia, 111 participants at two centers underwent assessments of negative symptoms, cognitive functioning, and aerobic fitness and 69 underwent additional structural magnetic resonance imaging. Multilevel Bayesian partial correlations were computed to quantify relationships between the variables of interest. The main finding was a positive association of aerobic fitness with right hippocampal GMV and WMVs in parahippocampal and several cerebellar regions. We found limited evidence for an association of aerobic fitness with cognitive functioning and negative symptoms. In summary, our results strengthen the notion that aerobic fitness and hippocampal plasticity are interrelated which holds implications for the design of exercise interventions in individuals with schizophrenia.

Background Quick symptomatic remission after the onset of psychotic symptoms is critical in schizophrenia treatment, determining the subsequent disease course and recovery. In this context, only every second patient with acute schizophrenia achieves symptomatic remission within three months of initiating antipsychotic treatment. The potential indication extension of clozapine—the most effective antipsychotic—to be introduced at an earlier stage (before treatment-resistance) is supported by several lines of evidence, but respective clinical trials are lacking. Methods Two hundred-twenty patients with acute non-treatment-resistant schizophrenia will be randomized in this double-blind, 8-week parallel-group multicentric trial to either clozapine or olanzapine. The primary endpoint is the number of patients in symptomatic remission at the end of week 8 according to international consensus criteria (‘Andreasen criteria’). Secondary endpoints and other assessments comprise a comprehensive safety assessment (i. e., myocarditis screening), changes in psychopathology, global functioning, cognition, affective symptoms and quality of life, and patients’ and relatives’ views on treatment. Discussion This multicentre trial aims to examine whether clozapine is more effective than a highly effective second-generation antipsychotics (SGAs), olanzapine, in acute schizophrenia patients who do not meet the criteria for treatment-naïve or treatment-resistant schizophrenia. Increasing the likelihood to achieve symptomatic remission in acute schizophrenia can improve the overall outcome, reduce disease-associated burden and potentially prevent mid- and long-term disease chronicity.

This study aims to investigate the barriers and facilitators to guideline adherence for the print format of the German schizophrenia guideline as well as for the concept of a digital living guideline for the first time. For this purpose, the schizophrenia guideline was transferred to a digital guideline format within the web-based tool MAGICapp. An online survey was performed under participation of mental healthcare professionals (medical doctors, psychologists/psychotherapists, psychosocial therapists, caregivers) in 17 hospitals for psychiatry in Southern Germany and a professional association for German neurologists and psychiatrists. 524 participants opened the survey, 439 completed the demographic questions and commenced the content-related survey and 309 provided complete data sets. Results indicate a higher occurrence of knowledge-related barriers for the living guideline. The print version is associated with more attitude-related and external barriers. Older professionals reported more attitude-related barriers to a living guideline compared to younger professionals. Differences between professions regarding barriers were found for both formats. Various barriers exist for both guideline formats and a need for facilitators was expressed across professions. Many of the mentioned obstacles and facilitators can be more easily addressed with living guidelines. However, also living guidelines face barriers. Thus, the introduction of these new formats alone cannot lead to sustainable behavior change regarding guideline adherence. Yet, living guidelines seem to be a cornerstone to improved and tailored guideline implementation as they facilitate to keep recommendations up to date and to address the need of individual professional groups.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(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 symptomś severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdown and sex-related differences in SSDs clinical trials and treatment strategies.

Background The hippocampal formation represents a key region in the pathophysiology of schizophrenia. Aerobic exercise poses a promising add-on treatment to potentially counteract structural impairments of the hippocampal formation and associated symptomatic burden. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is largely heterogeneous. Therefore, we conducted a systematic review and meta-analysis to assess the impact of aerobic exercise on total hippocampal formation volume. Additionally, we used data from a recent multicenter randomized-controlled trial to examine the effects of aerobic exercise on hippocampal formation subfield volumes and their respective clinical implications. Methods The meta-analysis comprised six studies that investigated the influence of aerobic exercise on total hippocampal formation volume compared to a control condition with a total of 186 people with schizophrenia (100 male, 86 female), while original data from 29 patients (20 male, 9 female) was considered to explore effects of six months of aerobic exercise on hippocampal formation subfield volumes. Results Our meta-analysis did not demonstrate a significant effect of aerobic exercise on total hippocampal formation volume in people with schizophrenia (g = 0.33 [−0.12 to 0.77]), p = 0.15), but our original data suggested significant volume increases in certain hippocampal subfields, namely the cornu ammonis and dentate gyrus. Conclusions Driven by the necessity of better understanding the pathophysiology of schizophrenia, the present work underlines the importance to focus on hippocampal formation subfields and to characterize subgroups of patients that show neuroplastic responses to aerobic exercise accompanied by corresponding clinical improvements.

Older Adults with Bipolar Disorder (OABD) represent a heterogeneous group, including those with early and late onset of the disorder. Recent evidence shows both groups have distinct clinical, cognitive, and medical features, tied to different neurobiological profiles. This study explored the link between polygenic risk scores (PRS) for bipolar disorder (PRS-BD), schizophrenia (PRS-SCZ), and major depressive disorder (PRS-MDD) with age of onset in OABD. PRS-SCZ, PRS-BD, and PRS-MDD among early vs late onset were calculated. PRS was used to infer posterior SNP effect sizes using a fully Bayesian approach. Demographic, clinical, and cognitive variables were also analyzed. Logistic regression analysis was used to estimate the amount of variation of each group explained by standardized PRS-SCZ, PRS-MDD, and PRS-BD. A total of 207 OABD subjects were included (144 EOBD; 63 LOBD). EOBD showed higher PRS-BD compared to LOBD (p = 0.005), while no association was found between age of onset and PRS-SCZ or PRS-MDD. Compared to LOBD, EOBD individuals also showed a higher likelihood for suicide attempts (p = 0.01), higher presence of psychotic symptoms (p = 0.003), higher prevalence of BD-I (p = 0.002), higher rates of familiarity for any psychiatric disorder (p = 0.004), and lower processing speed measured with Trail-Making Test part A (p = 0.03). OABD subjects with an early onset showed a greater genetic burden for BD compared to subjects with a late onset. These findings contribute to the notion that EOBD and LOBD may represent different forms of OABD, particularly regarding the genetic predisposition to BD.

Background Cognitive impairments are a hallmark of schizophrenia-spectrum disorders (SSD), contributing to poor treatment outcomes and a key treatment target. The Brief Assessment of Cognition in Schizophrenia (BACS) battery is a validated tool designed to evaluate affected core domains in SSD. The present study evaluated psychometric properties of the German version of the BACS in a representative sample of individuals with SSD and healthy control subjects. Methods N = 107 individuals with SSD and n = 175 healthy controls were assessed with the German version of the BACS. Diagnosis was confirmed with the Mini International Neuropsychiatric Interview according to DSM-V. Validity was assessed through pair-wise comparisons between SSD individuals and healthy controls and by using receiver operating characteristic analysis. Internal consistency as a measure of reliability was evaluated using McDonald's Omega and Cronbach's Alpha in addition to factor and principal component analysis. Results All individuals with SSD exhibited significantly lower z-scores across all BACS subtests and BACS composite scores (Z < -1.5) compared to healthy controls. ROC analysis revealed good diagnostic accuracy with an AUC of 0.83 (95%CI: 0.78,0.88, sensitivity = 0.75, specificity = 0.75). Similar results were observed in sub-cohorts comprising clinically stable SSD patients and those with younger ages (18–35 years old). A unidimensional structure, supported by McDonald's Omega (ω = 0.72) and principal component analysis, confirmed robust internal reliability. Conclusions The German BACS demonstrates strong validity and internal reliability when assessed in a representative case-control sample. This study provides an extensive normative dataset for individuals with SSD in German-speaking populations, facilitating future research and clinical assessments of cognition.

Objective Regular exercise significantly benefits mental health, yet its therapeutic potential in psychiatric care remains underutilised. Understanding the factors influencing physical activity in individuals with mental illness is crucial to realising its full therapeutic potential. Our study seeks to explore motivational and socio-demographic determinants affecting exercise habits in individuals with mental illness and compare them to those without mental illness. Design and setting Distribution of the link to a cross-sectional online survey at psychiatric clinics, practices, university events and sports clubs, via self-help group email lists and on social media. Methods An online survey using validated questionnaires supplemented with self-developed items was conducted. Statistical analysis encompassed unpaired t-tests and χ2 tests to compare individuals with and without mental illness, as well as multiple linear regression to investigate the relationship between childhood exercise experience, psychometrics and current physical activity behaviour in individuals with mental illness. Participants 1564 individuals (66.5% female) including 417 diagnosed with any kind of mental illness. Results In comparison with mentally healthy participants, individuals diagnosed with mental illness displayed notably lower activity levels (eg, engaging in regular physical activity 55.6% vs 69.3%, x2(1, n=1458) = 26.03, p<0.001), autonomous motivation (sport- und bewegungsbezogene Selbstkonkordanzskala Index: M=3.62, SD=3.07 vs M=4.62, SD=2.74, t(594.58)=5.4, p=0.009), self-efficacy expectancies (Allgemeine Selbstwirksamkeit Kurzskala: M=3.65, SD=0.81 vs M=4.10, SD=0.59, t(505.39)=9.76, p<0.001), and resilience (Brief Resilience Scale: M=2.81, SD=0.83 vs M=3.46, SD=0.70, t(555.52)=13.28, p<0.001), and a greater external locus of control (Internale-Externale-Kontrollüberzugung Scale: M=2.53, SD=0.89 vs M=2.13, SD=0.76, t(565.43)=−7.78, p<0.001). Throughout childhood and adolescence, they reported less activity (66.9% vs 78.0%, x2(1, n=1549) = 18.22, p<0.001) and lower grades in physical education (M=2.1, SD=0.8 vs M=1.8, SD=0.8, U=1 888 071.00, Z=−6.19, p<0.001). Individuals with mental illness favoured a structured sports programme led by professionals. Factors like self-concordance (ß=0.29, p<0.001), intrinsic motivation (ß=0.22, p=0.02), and self-efficacy expectations (ß=0.35, p<0.001) were strong predictors of current physical activity levels (eg, measured as training sessions per week) in this group. Conclusion There is a dire need for professionally supervised, small group exercise programmes for people with mental illness incorporating cognitive-behavioural elements, to better address their individual needs and to positively influence previously mentioned psychometric determinants. Furthermore, the importance of sport and physical activity in childhood, and especially in adolescence, was reaffirmed, underlining the paramount importance of youth sport programmes in long-term health promotion from a public health perspective.

Objectives: Roughly one in eight individuals presents with psychiatric disorders which were proposed to significantly affect oral health. This study compared oral health of 112 patients (mean 28 years), 31 with schizophrenia spectrum disorders (SSD) or 33 with major depression/bipolar disorders (MDD/BD) to 52 healthy controls (HCG). Materials and methods: Oral health parameters, including caries experience (decayed-missed-filled teeth/surfaces-index DMFT/DMFS), the presence of plaque (plaque-index PI) and periodontal health (bleeding on probing BOP, periodontal probing depths PPD%), were evaluated by examiners blinded to psychiatric diagnoses. Descriptive statistics summarized demographic and clinical data. Group differences and associations with dental outcomes were analyzed using Chi-square or Mann-Whitney-U tests. Logistic regression identified predictors of oral health. Results: Patients with SSD or MDD/BD resented with significantly oorer oral health than HCG regarding DMFT (SSD = 9; MDD/BD = 10; HCG = 2), DMFS (SSD = 10; MDD/BD = 12; HCG = 1), PI (SSD = 2; MDD/BD = 2; HCG = 1), BOP (SSD = 20%; MDD/BD = 17%; HCG = 3)% and PPD% (SSD = 1%; MDD/BD = 0%; HCG = 0%) and smoked more often. Differences regarding dental anxiety were not significant (p = 0.112). Subgroup analysis showed no differences between SSD and MDD/BD. Conclusions: SSD and MDD/BD and smoking are key contributors to poor dental health shown by significantly worse DMFT, DMFS and PI, BOP. Probably this might additionally be enhanced by concomitant medication, with multiple psychiatric medication being associated with poorer oral health regarding DMFT, PI and BOP. Clinical relevance: Routine dental care and personalized oral hygiene training to address disease-specific risks are desirable for individuals with SSD or MDD/BD.