Objectives: In early stage psychosis research is the identification of neurobiological correlates of vulnerability to schizophrenia an important hurdle.Methods: We conducted a systematic review of the neuroimaging publications on high-risk subjects with subsequent transition to psychosis (HR-T) and conducted a meta-analysis using the Cohen's d.Results: Out of 30 identified studies 25 met the inclusion criteria. sMRI 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) and reduced temporal cortex in first episode (FE) of psychosis subjects compared to HR-T.Compared to HR-NT, HR-T subjects showed in functional imaging studies reduced brain activation in prefrontal cortex, reduced neuronal density, increased membrane turnover in frontal and cingulate cortex and decreased availability of serotonine receptors in prefrontal 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.
Current opinion assumes epithelial integrity during spontaneous apoptotic cell death. We measured, for the first time, the local conductances associated with apoptoses and show leaks of up to 280 nS (mean 48 +/- 19 nS) in human intestinal epithelium. The results disprove the dogma that isolated cell apoptosis occurs without affecting the epithelial cell permeability barrier. After induction by tumor necrosis factor alpha (TNF-alpha) the apoptotic leaks were dramatically enhanced: not only was the frequency increased by threefold, but the mean conductance also increased by 12-fold (597+/-98 nS). Thus, apoptosis accounted for about half (56%) of the TNF-alpha-induced permeability increase whereas the other half was caused by degradation of tight junctions in nonapoptotic areas. Hence, spontaneous and induced apoptosis hollow out the intestinal barrier and may facilitate loss of solutes and uptake of noxious agents.
Our findings show that grey matter volume is lower in secondary-progressive than in relapsing-remitting disease. Grey matter volume explained physical and cognitive impairment better than white matter volume, and is itself associated with T2 and T1 lesion volume.
Abstract:Despite a large number of neuroimaging studies in schizophrenia reporting subtle brain abnormalities, we do not know to what extent such abnormalities reflect the effects of antipsychotic treatment on brain structure. We therefore systematically reviewed cross-sectional and follow-up structural brain imaging studies of patients with schizophrenia treated with antipsychotics. 30 magnetic resonance imaging (MRI) studies were identified, 24 of them being longitudinal and six cross-sectional structural imaging studies. In patients with schizophrenia treated with antipsychotics, reduced gray matter volume was described, particularly in the frontal and temporal lobes. Structural neuroimaging studies indicate that treatment with typical as well as atypical antipsychotics may affect regional gray matter (GM) volume. In particular, typical antipsychotics led to increased gray matter volume of the basal ganglia, while atypical antipsychotics reversed this effect after switching. Atypical antipsychotics, however, seem to have no effect on basal ganglia structure.
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