Medication adherence and cognitive performance in schizophrenia-spectrum and bipolar disorder: results from the PsyCourse Study.

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 < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performances, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not medication adherence.

Association between mitochondria-related genes and cognitive performance in the PsyCourse Study.

BACKGROUND: Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance. METHODS: We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program. RESULTS: We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests. LIMITATIONS: Moderate statistical power due to relatively small sample size. CONCLUSIONS: COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders.

Interplay between the genetics of personality traits, severe psychiatric disorders and COVID-19 host genetics in the susceptibility to SARS-CoV-2 infection.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus. AIMS: We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection. METHOD: Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data. RESULTS: We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10-5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies. CONCLUSIONS: We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.

Interplay between the Genetics of Personality Traits, severe Psychiatric Disorders, and COVID-19 Host Genetics in the Susceptibility to SARS-CoV-2 Infection

BackgroundThe SARS-CoV-2 pandemic, with all its impacts on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behavior and, therefore, the risk of contracting the virus. AimsWe examined overlapping genetic underpinnings between major psychiatric disorders, personality traits, and susceptibility to SARS-CoV-2 infection. MethodsLinkage disequilibrium score regression was used to explore the genetic correlations of COVID-19 susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n=1346) and the HeiDE (n=3266) study), polygenic risk scores were used to analyze if a genetic association between, psychiatric disorders, personality traits, and COVID-19 susceptibility exists in individual-level data. ResultsWe observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (p=1.47x10-5; rg=0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies. ConclusionsWe identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.

Medication Adherence in a Cross-Diagnostic Sample of Patients From the Affective-to-Psychotic Spectrum: Results From the PsyCourse Study.

INTRODUCTION: According to the World Health Organization, medication adherence is defined as the extent to which a person's behavior corresponds with an agreed recommendation from a healthcare provider. Approximately 50% of patients do not take their medication as prescribed, and non-adherence can contribute to the progress of a disease. For patients suffering from mental diseases non-adherence plays an important role. Various factors have been proposed as contributing to non-adherence, however the literature remains heterogeneous dependent on the analyzed patient subgroups. This study comprehensively evaluates the association of sociodemographic, clinical, personality and quality of life related factors with medication adherence by analyzing data from the PsyCourse study. The PsyCourse study is a large and cross-diagnostic cohort of psychiatric patients from the affective-to-psychotic spectrum. METHODS: The study sample comprised 1,062 patients from the PsyCourse study with various psychiatric diagnoses (mean [SD] age, 42.82 [12.98] years; 47.4% female). Data were analyzed to identify specific factors associated with medication adherence, and adherence was measured by a self-rating questionnaire. Odds ratios (OR) were estimated by a logistic regression for binary outcomes. Missing data were imputed using multiple imputation. RESULTS: The following factors showed the strongest association with medication adherence: never having used illicit drugs (OR, 0.71), number of prescribed antipsychotics (OR, 1.40), the personality trait conscientiousness (OR, 1.26), and the environmental domain of quality of life (OR, 1.09). CONCLUSION: In a large and cross-diagnostic sample, we could show that a higher level of conscientiousness, a higher number of antipsychotic medication, a better quality of life within the environmental domain, and the absence of substance abuse contribute to a better medication adherence independent of the underlying disorder.

Development of a fluid-bed coating process for soil-granule-based formulations of Metarhizium brunneum, Cordyceps fumosorosea or Beauveria bassiana.

AIM: Granule-based products of solid state fermented micro-organisms are available for biocontrol. Because liquid fermentation has several advantages, we investigated fluid-bed coating with liquid fermented biomass. METHODS AND RESULTS: Biomass containing mycelium or mycelium and submerged spores of the entomopathogenic fungi Metarhizium brunneum, Cordyceps fumosorosea and Beauveria bassiana were produced in liquid culture, separated and different biomass concentrations were adjusted. Based on the examined thermo-tolerance, we defined fluid-bed coating adjustments and investigated granule colonization and sporulation on granules. Granule colonization depended on the biomass concentration and strain. For C. fumosorosea and B. bassiana, concentrations of 0·003%dry weight resulted in nearly 100% granule colonization, for M. brunneum with concentrations of 0·7%dry weight in only 50%. The conidiation on granules in sterile soil was highly influenced by the moisture content. Because the granule colonization of M. brunneum was unsatisfactory, we pre-coated nutrients followed by coating with biomass, submerged spores or conidia. Malt extract had a positive effect on the granule colonization for biomass and submerged spores. Furthermore, aerial conidia can also be coated. CONCLUSIONS: Fluid-bed coating of fungal biomass is suitable for the development of granules. SIGNIFICANCE AND IMPACT OF THIS STUDY: With this technology, cost-efficient biocontrol products can be developed.

[Cold atmospheric pressure plasma for the treatment of acute and chronic wounds]. / Kaltes Atmosphärendruckplasma zur Behandlung akuter und chronischer Wunden.

BACKGROUND: Besides acute wounds (through trauma or surgical interventions), chronic wounds comprise a relatively large and heterogeneous group of diseases. These include leg ulcers with venous disease greatly prevailing arterial disease, diabetic foot syndrome, and pressure ulcers. Due to a considerable treatment resistance against such therapies, new and effective, additive treatment options especially for chronic wounds are needed. Wound treatment with cold atmospheric plasma (CAP) constitutes such an innovative option. OBJECTIVES: Current research regarding the efficacy of cold plasma for healing of acute and chronic wounds is summarized. MATERIALS AND METHODS: The literature on CAP applications in wound healing has been screened and reviewed. RESULTS: With CAP, several effects that promote wound healing can be simultaneously applied in one application. On the one hand, CAP exerts a strong and broad antimicrobial activity against biofilm. On the other hand, the plasma cocktail, which consists of reactive nitrogen and oxygen species, UV, and charged particles (electrical current), mediates tissue-stimulating, blood flow-promoting, and anti-inflammatory effects. Marked germ reduction on wounds and accelerated wound healing have already been convincingly demonstrated in controlled clinical studies. CONCLUSIONS: The comprehensive CAP study landscape with structured case report summaries and randomized case-control studies allows the conclusion that CAP is safe, effective, and easy to handle for wound treatment. The utilization of CAP in addition to standard wound treatments is starting to enter routine clinical practice.

Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins.

The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h2 = 0.28-0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.

[Current indications for plasma therapy in dermatology]. / Aktuelle Indikationen der Plasmatherapie in der Dermatologie.

BACKGROUND: Plasma medicine is gaining increasing interest and provides a multitude of dermatological applications. Cold atmospheric pressure plasma (CAP) can be used in clinical applications without harming the treated tissue or in a tissue destructive manner. It consists of a complex mixture of biologically active agents, which can act synergistically on the treated material or tissue. OBJECTIVES: A summary of the current research findings regarding dermatological applications of CAP is provided. METHODS: Literature on CAP applications in dermatology has been screened and summarized. RESULTS: CAP exerts antimicrobial, tissue-stimulating, blood-flow-stimulating but also pro-apoptotic effects. By exploiting these properties, CAP is successfully applied for disinfection and treatment of chronic ulcerations. Furthermore, positive effects of CAP have been shown for the treatment of tumors, actinic keratosis, scars, ichthyosis, atopic eczema as well as for alleviation of pain and itch. CONCLUSIONS: While the use of CAP for disinfection and wound treatment has already moved into clinical practice, further applications such as cancer treatment are still exploratory.

alpha1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients.

The airways of cystic fibrosis (CF) patients are characterised by neutrophils that release high amounts of elastase overwhelming the local antiprotease shield. Inhalation of alpha(1)-antitrypsin (AAT) may restore the protease-antiprotease balance and attenuate airway inflammation in CF airways. The aims of the present study were: 1) to assess the best deposition region for inhaled AAT by two different inhalation strategies; and 2) to examine the effect of 4 weeks of AAT inhalation on lung function, protease-antiprotease balance and airway inflammation in CF patients. In a prospective, randomised study, 52 CF patients received a daily deposition by inhalation of 25 mg AAT for 4 weeks targeting their peripheral or bronchial compartment. The levels of elastase activity, AAT, pro-inflammatory cytokines, neutrophils, immunoglobulin G fragments and the numbers of Pseudomonas aeruginosa were assessed in induced sputum before and after the inhalation period. Inhalation of AAT increased AAT levels and decreased the levels of elastase activity, neutrophils, pro-inflammatory cytokines and the numbers of P. aeruginosa. However, it had no effect on lung function. No difference was found between the peripheral and bronchial inhalation mode. In conclusion, although no effect on lung function was observed, the clear reduction of airway inflammation after alpha(1)-antitrypsin treatment may precede pulmonary structural changes. The alpha(1)-antitrypsin deposition region may play a minor role for alpha(1)-antitrypsin inhalation in cystic fibrosis patients.

[Attitudes towards predictive genetic testing for Alzheimer's disease]. / Einstellung zu genetischen Untersuchungen auf Alzheimer-Demenz.

Most neuropsychiatric disorders have a complex aetiology. Discovery of the underlying genetics will provide insights into the disorders and allow the subsequent development of therapeutic interventions based upon an understanding of causality. The first vulnerability genes in Alzheimer's disease (AD) have been identified. The contribution of each vulnerability gene to the disorder is limited and does not enable prediction of course and onset in individual cases, only modification of the a priori risk. However, people may wish to be informed about this modification. Professionals have not favoured this form of predictive testing due to an awareness of its limitations and its potential for harm. However, little is known about public attitudes and understanding of such genetic testing in neuropsychiatric disorders. The aim of our study was to assess the attitudes of the general population and to explore the influence on these attitudes of knowledge about the illness and the understanding of risk information. In our study, a representative sample of the German general population (n=2001), relatives of patients with Alzheimer's disease (n=101) and physicians (n=43) were interviewed about their attitudes towards genetic tests for Alzheimer's disease and their perception and interpretation of risk information. To assess the influence of genetic counselling on these factors, 234 people were questioned before, and four weeks after, they were provided with detailed relevant information. Our results indicate that a substantial proportion of the German population (57%) is in favour of psychiatric genetic testing for AD in general. Even when the explanatory power of a genetic test is limited, a substantial proportion of the population (47%) expressed an interest in genetic testing. Counselling slightly decreased the interest in having a genetic test for oneself (from 47% to 38%). Physicians were more hesitant than both relatives and the general population concerning predictive genetic testing. Only a minority (11%) favoured prenatal genetic testing. Our results also show that both knowledge about AD and the capacity to interpret risk estimates are limited. While physicians' estimation of their personal risk for developing AD approximated to the actual average risk for the population, people in the general population and the relatives of AD patients tended to overestimate their personal risk. However, most of the general population still perceived this risk as average or low. While most physicians could correctly interpret information regarding the probability of risk, only one third of AD patients' relatives or members of the general population could. As the decision of an individual to undergo predictive testing relies mainly on his understanding of risk, the ability to correctly interpret risk information will be of crucial importance in the future. From a medical perspective, the prevailing approach of professional associations to genetic testing appears reasonable and therefore should not be changed at present.

Effects of arousing emotional scenes on the distribution of visuospatial attention: changes with aging and early subcortical vascular dementia.

BACKGROUND: The modulation of attention by emotionally arousing stimuli is highly important for each individual's social function. Disturbances of emotional processing are a supportive feature for the diagnosis of subcortical vascular dementia (SVD). We address here whether these disturbances might be useful as an early disease marker. METHODS: In order to examine the modulation of visual attention by emotionally arousing stimuli of different valence, 12 elderly patients with early SVD, 12 age-comparable healthy adults and 12 young healthy subjects were studied while looking at pairs of pictures from the International Affective Picture Battery that were either neutral-neutral, neutral-positive or neutral-negative in terms of emotional content. Eye movements were recorded with an infrared eye-tracking system. The direction of the first saccade and the dwell time during the 10 s of presentation were measured and compared among groups with parametric tests. RESULTS: All subjects showed a modulation of initial attentional orienting as well as a higher percentage of dwell time towards the pictures containing emotional material. Patients with SVD and old controls did not differ in either experimental measure. Young patients showed a stronger bias towards emotionally negative material than both groups of older individuals. CONCLUSIONS: Modulation of visuospatial attention is preserved in early SVD. This might have implications for therapeutic interventional approaches. A weakened sustained attention towards negative but not positive emotional pictures in the elderly is in accordance with the socioemotional selectivity theory, describing a relative selection of positive stimuli with aging.

Psychosocial work factors and dementia.

AIMS: To evaluate the association between psychosocial workplace factors and dementia in a case-control study. METHODS: Patients with dementia (aged 55-99 years) were recruited from 23 general practices in the city of Frankfurt-on-Main and surrounding area in 1998-2000. Of these, 108 were suffering from possible Alzheimer's disease, 59 from possible vascular dementia, and 28 from secondary or unclassified dementia. A total of 229 control subjects (aged 60-94 years) was recruited from the same study region: 122 population controls and 107 dementia-free ambulatory patients. A detailed job history was elicited in a structured personal interview (next-of-kin interviews of cases). Psychosocial work exposure was assigned to cases and control subjects by linking lifetime job histories with a Finnish job-exposure matrix. Data were analysed using logistic regression, to control for age, region, sex, dementia in parents, education, smoking, and the psychosocial network at age 30. RESULTS: There were decreased odds ratios for high challenge at work, high control possibilities at work, and high social demands at work. High risks for error at work revealed a significant positive association with the diagnosis of dementia. Restriction of the analysis to cases with possible Alzheimer's disease or to cases with possible vascular dementia led to similar results. CONCLUSIONS: These results support a role for psychosocial work factors in the aetiology of dementia. As an alternative explanation, people might have chosen jobs with poor work factors due to preclinical dementia, which becomes clinically manifest decades later.

[Virtual cystoscopy with reduced tube current: an alternative to cystoscopy?]. / Virtuelle Zystoskopie mit reduziertem Röhrenstrom: Eine Alternative zur Zystoskopie?

PURPOSE: Virtual cystoscopy at different mAs settings in patients with tumors of the bladder in comparison with cystoscopy and axial CT. MATERIALS AND METHODS: The study included 28 patients with bladder tumors and 28 patients without tumors as control group. The bladder was distended with air and scanned at two different mAs settings (protocol 1 and 2). The radiation exposure was reduced by 82 % for protocol 2 in comparison with protocol 1. Three readers compared virtual cystoscopy with cystoscopy and axial CT as to tumor location and size. Sensitivity, specificity and accuracy were calculated. RESULTS: Of the 47 tumors seen at cystoscopy, all readers detected 45 tumors by virtual cystoscopy using protocol 1 and 44 tumors using protocol 2, with p > 0.05 in comparison with cystoscopy. Virtual cystoscopy showed higher sensitivity than axial CT (97.2 % vs. 86.5 % for protocol 1) and (96.5 % vs. 86.5 % for protocol 2) with the same specificity (100 %). The accuracy was 0.982 for protocol 1 and 0.978 for protocol 2. In comparison with virtual cystoscopy, axial CT shoved more often over- and underestimation of the tumor size. CONCLUSION: Virtual cystoscopy at reduced mAs setting is a modality suitable for the detection of polypoid tumors, but does not provide data of the mucosa and thus cannot replace cystoscopy yet.

Diagnostic potential of virtual cystoscopy of the bladder: MRI vs CT. Preliminary report.

The aim of the study was to evaluate the diagnostic potential of the half-Fourier acquired single-shot turbo spin echo (HASTE) sequence for MRI cystoscopy compared with CT cystoscopy and the gold standard conventional cystoscopy. The MRI- and CT cystoscopy was performed in 29 patients with bladder tumors documented at cystoscopy and a control group using a 1.5-T unit (6-mm slice thickness) and a helical CT (3-mm collimation, pitch 1) after filling the bladder with air. Axial MRI and CT images were transferred to a workstation for application of virtual cystoscopy and compared with routine cystoscopy. Axial images and virtual cystoscopies were read by three readers for size and location of tumors. Forty-seven tumors were diagnosed at cystoscopy (12<1 cm, 35>/=1 cm). The sensitivity for detection of tumors smaller than 1 cm was 88.9% at MRI cystoscopy and 100% for tumors of 1 cm or larger. These results were not statistically different from the other modalities. Three tumors smaller than 1 cm were not detected at CT cystoscopy, four not all identical at MRI cystoscopy. One tumor with a wall thickening was detected on axial CT and MR images and CT cystoscopy by all observers, but only by two at MRI cystoscopy. The MRI cystoscopy is a diagnostic modality with results comparable to conventional and CT cystoscopy.

Osteopetrosis, femoral fracture, and chronic osteomyelitis caused by Staphylococcus aureus small colony variants (SCV) treated by girdlestone resection--6-year follow-up.

Chronic osteomyelitis caused by Staphylococcus aureus small colony variants in combination with osteopetrosis is a unique combination of disorders that confronted us with major challenges. The therapeutic approach included four serial debridements and antimicrobial therapy. The aggressive treatment led to an instability of the brittle and hard osteopetrotic bone, and after 11 weeks, a fracture of the femoral neck occurred. A salvage procedure of the femur was performed, and the cultures obtained during this intervention remained negative. At a 6-year follow-up, the girdlestone situation still showed an acceptable functional outcome without any recurrence of osteomyelitis.

[The effect of psychosocial factors on risk of dementia]. / Der Einfluss von psychosozialen Faktoren auf das Demenzerkrankungsrisiko.

In the etiology of dementia several genetic and various environmental factors are assumed to interact. Most epidemiological studies on risk factors have focused on "constitutional" factors like age, sex, birth order, dementia in the family and "life style" factors like smoking and alcohol consumption. Only few studies have investigated the role of psychosocial factors at work and during leisure time on the risk to develop dementia. Our paper gives a systematic review of all published results of controlled studies about psychosocial risk factors. A positive association has been observed between dementia and living alone, having no close social ties, not participating in social and leisure activities, and never having married. Recent studies have found that Alzheimer's disease in particular is negatively associated with diversity of activities and intensity of intellectual activities and positively associated with psychosocial inactivity, unproductive working style, living with a dominant spouse and with physical inactivity.

[Effect of daily living-related cognitive training on attention and memory performance of persons with dementia]. / Der Einfluss eines alltagsbezogenen kognitiven Trainings auf die Aufmerksamkeits- und Gedächtnisleistung von Personen mit Demenz.

There are few results of controlled studies about psychological interventions, i.e. training of cognitive functions in dementing illnesses. Most frequently very specific memory strategies are trained, (the effects of) which cannot be generalized to activities of daily living. Thus, a memory training program was developed considering the different cognitive abilities of the participants and which was meant to be generalized to daily tasks. Short-term and long-term memory were trained as well as activities of daily living in 12 lessons for a period of 6 weeks. We can show significant improvements of attention and memory performance in our experimental group in comparison to the control group.