Insular volume abnormalities associated with different transition probabilities to psychosis

Background Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM). Method We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC. Results The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group. Conclusions GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilitie

Validation of T-Track® CMV to assess the functionality of cytomegalovirus-reactive cell-mediated immunity in hemodialysis patients

Background: Uncontrolled cytomegalovirus (CMV) replication in immunocompromised solid-organ transplant recipients is a clinically relevant issue and an indication of impaired CMV-specific cell-mediated immunity (CMI). Primary aim of this study was to assess the suitability of the immune monitoring tool T-Track (R) CMV to determine CMV-reactive CMI in a cohort of hemodialysis patients representative of patients eligible for renal transplantation. Positive and negative agreement of T-Track (R) CMV with CMV serology was examined in 124 hemodialysis patients, of whom 67 (54%) revealed a positive CMV serostatus. Secondary aim of the study was to evaluate T-Track (R) CMV performance against two unrelated CMV-specific CMI monitoring assays, QuantiFERON (R)-CMV and a cocktail of six class I iTAg (TM) MHC Tetramers. Results: Positive T-Track (R) CMV results were obtained in 90% (60/67) of CMV-seropositive hemodialysis patients. In comparison, 73% (45/62) and 77% (40/52) positive agreement with CMV serology was achieved using QuantiFERON (R)-CMV and iTAg (TM) MHC Tetramer. Positive T-Track (R) CMV responses in CMV-seropositive patients were dominated by pp65-reactive cells (58/67 [ 87%]), while IE-1-responsive cells contributed to an improved (87% to 90%) positive agreement of T-Track (R) CMV with CMV serology. Interestingly, T-Track (R) CMV, QuantiFERON (R)-CMV and iTAg (TM) MHC Tetramers showed 79% (45/57), 87% (48/55) and 93% (42/45) negative agreement with serology, respectively, and a strong inter-assay variability. Notably, T-Track (R) CMV was able to detect IE-1-reactive cells in blood samples of patients with a negative CMV serology, suggesting either a previous exposure to CMV that yielded a cellular but no humoral immune response, or TCR cross-reactivity with foreign antigens, both suggesting a possible protective immunity against CMV in these patients. Conclusion: T-Track (R) CMV is a highly sensitive assay, enabling the functional assessment of CMV-responsive cells in hemodialysis patients prior to renal transplantation. T-Track (R) CMV thus represents a valuable immune monitoring tool to identify candidate transplant recipients potentially at increased risk for CMV-related clinical complications

Activation and modulation of antiviral and apoptotic genes in pigs infected with classical swine fever viruses of high, moderate or low virulence

The immune response to CSFV and the strategies of this virus to evade and suppress the pigs’ immune system are still poorly understood. Therefore, we investigated the transcriptional response in the tonsils, median retropharyngeal lymph node (MRLN), and spleen of pigs infected with CSFV strains of similar origin with high, moderate, and low virulence. Using a porcine spleen/intestinal cDNA microarray, expression levels in RNA pools prepared from infected tissue at 3 dpi (three pigs per virus strain) were compared to levels in pools prepared from uninfected homologue tissues (nine pigs). A total of 44 genes were found to be differentially expressed. The genes were functionally clustered in six groups: innate and adaptive immune response, interferon-regulated genes, apoptosis, ubiquitin-mediated proteolysis, oxidative phosphorylation and cytoskeleton. Significant up-regulation of three IFN-γ-induced genes in the MRLNs of pigs infected with the low virulence strain was the only clear qualitative difference in gene expression observed between the strains with high, moderate and low virulence. Real-time PCR analysis of four response genes in all individual samples largely confirmed the microarray data at 3 dpi. Additional PCR analysis of infected tonsil, MRLN, and spleen samples collected at 7 and 10 dpi indicated that the strong induction of expression of the antiviral response genes chemokine CXCL10 and 2′–5′ oligoadenylate synthetase 2, and of the TNF-related apoptosis-inducing ligand (TRAIL) gene at 3 dpi, decreased to lower levels at 7 and 10 dpi. For the highly and moderately virulent strains, this decrease in antiviral and apoptotic gene expression coincided with higher levels of virus in these immune tissues

Neuroimaging predictors of transition to psychosis : a systematic review and meta-analysis

OBJECTIVES: In early stage psychosis research the identification of neurobiological correlates of vulnerability to schizophrenia is an important hurdle. METHODS: We systematically reviewed the neuroimaging publications on high-risk subjects with subsequent transition to psychosis (HR-T) and conducted a meta-analysis calculating the effect size Cohen's d. RESULTS: Out of 30 identified studies 25 met the inclusion criteria. Structural (s)MRI studies showed small to medium effect sizes of decreased prefrontal, cingulate, insular and cerebellar gray matter volume in HR-T compared to high-risk subjects without transition (HR-NT). Meta-analysis revealed relatively larger whole brain volumes in HR-T compared to HR-NT subjects (mean Cohen's d 0.36, 95% CI 0.27-0. 46). Compared to HR-NT, HR-T subjects showed in functional imaging studies reduced brain activation in prefrontal cortex, reduced neuronal density, and increased membrane turnover in frontal and cingulate cortex with medium to large effect sizes. CONCLUSIONS: Despite methodological differences between studies, structural and neurochemical abnormalities in prefrontal, anterior cingulate, medial temporal and cerebellar cortex might be predictive for development of psychosis within HR subjects