Level of structural integration in people with schizophrenia and schizoaffective disorders - applicability and associations with clinical parameters.

Introduction: The psychic structure of people with psychosis has been the subject of theoretical and qualitative considerations. However, it has not been sufficiently studied quantitatively. Therefore, the aim of this study was to explore the structural abilities of people diagnosed with schizophrenia and schizoaffective psychosis using the Levels of Structural Integration Axis of the Operationalized Psychodynamic Diagnosis System (OPD-2-LSIA). The study aimed to determine possible associations between the OPD-2-LSIA and central parameters of illness. Additionally, possible structural differences between people diagnosed with schizophrenia and schizoaffective psychosis were tested. Methods: This cross-sectional study included 129 outpatients with schizophrenia or schizoaffective disorders. Measures of structural integration, symptom load, severity of illness, cognition, and social functioning were obtained. Descriptive statistics were used to analyze the overall structural level and the structural dimensions. Correlation coefficients were computed to measure the associations between OPD-2-LSIA and variables regarding the severity of illness and psychosocial functioning. Regression models were used to measure the influence of illness-related variables on OPD-2-LSIA, and the influence of OPD-2-LSIA on psychosocial functioning. Participants diagnosed with schizophrenia and schizoaffective disorders were examined with regard to possible group differences. Results: The results of the OPD-2-LSIA showed that the overall structural level was between 'moderate to low' and 'low level of structural integration'. Significant correlations were found between OPD-2-LSIA and psychotic symptoms (but not depressive symptoms), as well as between OPD-2-LSIA and psychosocial functioning. It was found that variables related to severity of illness had a significant impact on OPD-2-LSIA, with psychotic, but not depressive symptoms being significant predictors. OPD-2-LSIA was found to predict psychosocial functioning beyond symptoms and cognition. No significant differences were found between participants with schizophrenia and schizoaffective psychosis. There was also no correlation found between OPD-2-LSIA and depressive symptomatology (except for the subdimension Internal communication). Discussion: Contrary to theoretical assumptions, the results of the study show a heterogenous picture of the psychic structure of people with psychosis. The associations between OPD-2-LSIA and severity of illness, particularly psychotic symptomatology, as well as the influence of OPD-2-LSIA on psychosocial functioning, are discussed.

Insight and Outcome in Long-Term Psychotherapies of Depression.

Objectives: In different therapeutic approaches, insight is acknowledged as an important part of patient's therapeutic change process. We examined whether the level of insight (1) differs between psychoanalytic (PA), psychodynamic (PD) and cognitive-behavioral therapy (CBT), and (2) predicts long-term symptomatic outcome. Methods: A completer sample of 67 depressed patients from the Munich Psychotherapy Study was analyzed. Symptoms were assessed with Beck Depression Inventory (BDI) and Symptom Checklist-Revised (SCL-90-R) at pre-treatment and three-year follow-up. Insight was assessed from 242 sessions of mid-therapy phase with the Experiencing Scale. Results: The general level of insight was higher in PA as compared to CBT, and associated with lower depressive symptoms (BDI) across all three therapeutic modalities at three-year follow-up. Insight was unrelated to general distress (SCL-90-R). Exploratory analyses suggested that patients treated with PA showed higher levels of insight especially in high quality sessions (assessed by therapist). Patients for whom the extent of insight was positively linked to session quality, suffered from more depressive symptoms at three-year follow-up than patients gaining insight when session quality was low. Conclusion: Insight differs between PA and CBT and may be a common change mechanism in long-term psychotherapies.

Levels of Structural Integration Mediate the Impact of Metacognition on Functioning in Non-affective Psychosis: Adding a Psychodynamic Perspective to the Metacognitive Approach.

Synthetic metacognition is defined by integrative and contextualizing processes of discrete reflexive moments. These processes are supposed to be needed to meet intrapsychic as well as interpersonal challenges and to meaningfully include psychotic experience in a personal life narrative. A substantial body of evidence has linked this phenomenon to psychosocial functioning and treatment options were developed. The concept of synthetic metacognition, measured with the Metacognition Assessment Scale-Abbreviated (MAS-A), rises hope to bridge gaps between therapeutic orientations and shares valuable parallels to modern psychodynamic constructs, especially the 'levels of structural integration' of the Operationalized Psychodynamic Diagnosis (OPD-2). As theoretical distinctions remain, aim of this study was to compare the predictive value of both constructs with regard to psychosocial functioning of patients with non-affective psychoses, measured with the International Classification of Functioning, Disability and Health (MINI-ICF-APP). It was further explored if levels of structural integration (OPD-LSIA) would mediate the impact of metacognition (MAS-A) on function (MINI-ICF-APP). Expert ratings of synthetic metacognition (MAS-A), the OPD-2 'levels of structural integration' axis (OPD-LSIA), psychosocial functioning (MINI-ICF-APP) and assessments of general cognition and symptoms were applied to 100 individuals with non-affective psychoses. Whereas both, MAS-A and OPD-LSIA, significantly predicted MINI-ICF-APP beyond cognition and symptoms, OPD-LSIA explained a higher share of variance and mediated the impact of MAS-A on MINI-ICF-APP. Levels of structural integration, including the quality of internalized object representations and unconscious interpersonal schemas, might therefore be considered as valuable predictors of social functioning and as one therapeutic focus in patients with non-affective psychoses. Structural integration might go beyond and form the base of a person's actual reflexive and metacognitive capabilities. Psychotherapeutic procedures specific for psychoses may promote and challenge a patient's metacognitive capacities, but should equally take the need for maturing structural skills into account. Modern psychodynamic approaches to psychosis are shortly presented, providing concepts and techniques for the implicit regulation of interpersonal experience and aiming at structural integration in this patient group.

Biofilm formation and transcriptome analysis of Streptococcus gallolyticus subsp. gallolyticus in response to lysozyme.

Streptococcus gallolyticus subsp. gallolyticus is a commensal bacterium of the human gastrointestinal tract, and a pathogen causing infective endocarditis and other biofilm-associated infections via exposed collagen. This study focuses on the characterization of the biofilm formation and collagen adhesion of S. gallolyticus subsp. gallolyticus under different conditions. In this study, it has been observed that the isolate UCN 34 is resistant to 20 mg/ml lysozyme in BHI medium, whereas the strain BAA-2069 builds more biofilm in the presence of lysozyme compared to in a control of BHI without lysozyme. A transcriptome analysis with whole genome microarrays of these two isolates in BHI medium with lysozyme compared to control without lysozyme revealed changes in gene expression levels. In the isolate BAA-2069, 67 genes showed increased expression in the presence of lysozyme, while in the isolate UCN 34, 165 genes showed increased expression and 30 genes showed decreased expression through lysozyme treatment. Products of genes which were higher expressed are in involved in transcription and translation, in cell-wall modification, in hydrogen peroxide resistance and in bacterial immunity. Furthermore, the adhesion ability of different strains of S. gallolyticus subsp. gallolyticus to collagen type I and IV was analyzed. Thereby, we compared the adhesion of 46 human isolates with 23 isolates from animals. It was shown that the adhesion ability depends significantly on whether the isolate was isolated from human or animal. For example, high adhesion ability was observed for strain UCN 34 isolated from an infective endocarditis patient, whereas strain DSM 16831 isolated from koala feces adhered only marginally to collagen. Full genome microarray analysis of these two strains revealed strain-dependent gene expression due to adhesion. The expression of 25 genes of a transposon and 15 genes of a phage region in strain DSM 16831 were increased, which corresponds to horizontal gene transfer. Adherence to collagen in strain UCN 34 led to higher expression of 27 genes and lower expression of 31 genes. This was suggestive of a change in nutrient uptake.

Strain-dependent interactions of Streptococcus gallolyticus subsp. gallolyticus with human blood cells.

BACKGROUND: Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) is the causative pathogen in up to 20% of streptococcal-induced infective endocarditis (IE) cases. However, the underlying mechanisms of pathogenesis in S. gallolyticus have not yet been solved. Pathogens causing IE need to employ virulent strategies to initiate and establish infections, such as escape the bloodstream, invade the host-cell, and persist intracellularly. In this study, we examined the induction of inflammation by different S. gallolyticus strains in relation to their survival in whole blood and cell culture models as well as their ability to induce platelet aggregation. Phagocytosis of these bacteria by macrophages, followed by intracellular survival, was also quantified. METHODS: In whole blood and THP-1 cell culture assays bacterial growth kinetics was determined by plating, followed by colony counting. Induction of interleukin (IL)-6 expression in whole blood of three healthy volunteers, caused by different strains, was quantified by ELISA. Gene expression of cytokines (IL1B, IL6 and IL8) was quantified by real-time PCR after stimulating THP-1 monocytes with bacteria. Induction of platelet aggregation was analyzed by light transmission aggregometry using the BORN method. A macrophage model was used to analyze phagocytosis of strains and their survival in macrophages within 48 h. RESULTS: Strains promoted IL-6 secretion in a time-dependent fashion. For example, DSM16831 induced IL-6 secretion in whole blood earlier than other isolates, and was eliminated in the whole blood of one volunteer, whereas UCN34 could grow. Platelet aggregation depended on the different isolates used and on the individual platelet donor. Two strains (AC1181 and 010672/01) induced cytokine gene expression in THP-1 monocytes only marginally, compared to other strains. The phagocytosis rate of S. gallolyticus isolates differed significantly, and the isolates UCN34 and BAA-2069 could persist for a considerable time in the phagocytes. CONCLUSION: The strain-dependent differences of S. gallolyticus isolates, observed during interaction with human blood cells, support the hypotheses that divergences in individual virulence factors determine a distinct pathogenicity of the isolates. These data constitute an additional step towards the elucidation of mechanisms in the complex, multifactorial pathogenesis of this IE pathogen.

Transcriptome analysis of Streptococcus gallolyticus subsp. gallolyticus in interaction with THP-1 macrophage-like cells.

BACKGROUND: Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) is a pathogen of infective endocarditis. It was observed previously that this bacterium survives longer in macrophages than other species and the phagocytic uptake by and survival in THP-1 macrophages is strain-dependent. METHODS: The phagocytosis assay was performed with THP-1 macrophages. S. gallolyticus specific whole genome microarrays were used for transcriptome analysis. RESULTS: Better survival in macrophages was observed for UCN34, BAA-2069 and ATCC43143 than for DSM16831 and LMG17956. S. gallolyticus strains show high resistance to tested bactericidal agents (acid, lysozyme and hydrogen peroxide). S. gallolyticus stimulates significant lower cytokine gene expression and causes less lysis of macrophages compared to the control strain Staphylococcus aureus. S. gallolyticus reacts to oxidative burst with a higher gene expression of NADH oxidase initially at the early phase. Expression of genes involved in D-alanylation of teichoic acid, carbohydrate metabolism and transport systems were upregulated thereafter. CONCLUSION: S. gallolyticus is very resistant to bactericidal agents normally causing degradation of bacteria in phagolysosomes. Additionally, the D-alanylation of teichoic acid is an important factor for survival.

Complete Genome Sequence of the Streptococcus gallolyticus subsp. gallolyticus Strain DSM 16831.

Streptococcus gallolyticus subsp. gallolyticus DSM 16831 is an intriguing strain because of its low virulent phenotype compared to other isolates. We present here the complete genome sequence for this strain isolated from koala feces.

Genetic variants in genes of the inflammatory response in association with infective endocarditis.

AIMS: Inflammation in infective endocarditis (IE) is a complex network including interactions of inflammatory cytokines and other components of host response. Certainly, any variation in this network could influence susceptibility or disease progression of IE. In this study, 14 single nucleotide variants (SNVs) in genes coding for interleukin-1ß, interleukin-6, interleukin-10, toll-like receptor-4, tumor necrosis factor-α, selectin E and intercellular adhesion molecule-1 were analyzed for an association with susceptibility to IE and correlated with disease-related laboratory parameters. Furthermore, the occurrence of SNVs was examined to elucidate pathogen-dependent associations. METHODS AND RESULTS: The distribution of SNVs was determined in IE-patients and healthy blood donors by RFLP analysis. White blood cells (WBC) were counted using flow cytometry, concentration of C-reactive protein and procalcitonin was measured immunologically. Interleukin-6 c.471+870G>A genotypes differed significantly between IE patients and controls. The frequency of the heterozygote genotype GA was considerably higher in the patient group (68.9% vs. 43.8%, Pc<0.0003). Interleukin-6 c.-237 minor allele frequency was increased in patients, although not statistically significant. Additionally, we detected a potential relation between interleukin-1ß c.315C>T and IE. Pathogen-dependent analysis showed no significantly associated subgroup in relation to IE susceptibility, but gave hints towards alterations regarding Enterococcus-caused IE cases. Patients with genotype selectin-E c.-19 GT tend to have higher preoperative WBC counts than patients with genotype GG. We further showed an association between two interleukin-1ß SNVs and laboratory biomarkers. CONCLUSION: This study shows genetic predispositions for the establishment of IE. Furthermore, correlation of SNVs with disease-related biomarkers suggests a role of genetic variants regarding the inflammatory response in IE.