Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia

BACKGROUND: The identification of schizophrenia biomarkers is a crucial step towards improving current diagnosis, developing new presymptomatic treatments, identifying high-risk individuals and disease subgroups, and assessing the efficacy of preventative interventions at a rate that is not currently possible. METHODS AND FINDINGS: (1)H nuclear magnetic resonance spectroscopy in conjunction with computerized pattern recognition analysis were employed to investigate metabolic profiles of a total of 152 cerebrospinal fluid (CSF) samples from drug-naïve or minimally treated patients with first-onset paranoid schizophrenia (referred to as “schizophrenia” in the following text) and healthy controls. Partial least square discriminant analysis showed a highly significant separation of patients with first-onset schizophrenia away from healthy controls. Short-term treatment with antipsychotic medication resulted in a normalization of the disease signature in over half the patients, well before overt clinical improvement. No normalization was observed in patients in which treatment had not been initiated at first presentation, providing the first molecular evidence for the importance of early intervention for psychotic disorders. Furthermore, the alterations identified in drug-naïve patients could be validated in a test sample set achieving a sensitivity and specificity of 82% and 85%, respectively. CONCLUSIONS: Our findings suggest brain-specific alterations in glucoregulatory processes in the CSF of drug-naïve patients with first-onset schizophrenia, implying that these abnormalities are intrinsic to the disease, rather than a side effect of antipsychotic medication. Short-term treatment with atypical antipsychotic medication resulted in a normalization of the CSF disease signature in half the patients well before a clinical improvement would be expected. Furthermore, our results suggest that the initiation of antipsychotic treatment during a first psychotic episode may influence treatment response and/or outcome

Planar lamellae and onions: a spatially resolved rheo-NMR approach to the shear-induced structural transformations in a surfactant model system

The shear-induced transformations between oriented planar lamellae and a state of closely packed multilamellar vesicles (MLVs) in a lyotropic nonionic surfactant model system were studied by the combination of nuclear magnetic resonance (NMR) spectroscopy and diffusometry with magnetic resonance imaging (MRI). (2)H NMR imaging confirmed the discontinuous nature of the transition from onions to planar lamellae, revealing the spatial coexistence of both states within the gap of the cylindrical Couette geometry. On the other hand, NMR diffusion measurements in three principal directions and at various values of strain strongly suggest that a multi-lamellar cylindrical or undulated intermediate structure exists during the continuous and spatially homogeneous transition from planar lamellae to MLVs

Elektronenmikroskopische Präparation biologischer Objekte ohne Dünnschnittechnik durch Oberflächenspreitung und Kritische Punkt-Trocknung : Ein methodischer Beitrag.

Die Methode der Oberflächenspreitung und der Kritischen Punkt-Trocknung zur elektronenmikroskopischen Präparation ungeschnittener biologischer Objekte wird im einzelnen beschrieben. Die Methode erlaubt, grobmorphologische Veränderungen von Erythrocytenschatten zu beurteilen, Virusteilchen in Zellen nachzuweisen und den inneren Aufbau einzelner Chromosomen zu charakterisieren