Researchers have identified a calcium binding protein that, at increased levels, may be associated with the negative symptoms of schizophrenia. This protein, S100B, promotes neuronal survival and regeneration at normal levels. At abnormally high levels, it is neurotoxic and induces the apoptosis of neurons and glial cells.
ARTICLE: "Increased S100B blood levels in unmedicated and treated schizophrenia patients are correlated with negative symptomatology"
AUTHORS: M Rothermundt, U Missler, V Arolt, M Peters, J Leadbeater, M Wiesmann, S Rudolf, KP Wandinger and H Kirchner
Department of Psychiatry, University of Muenster School of Medicine, Albert-Schweitzer-Str. 11, D-48129 Muenster, Germany; Department of Neuroradiology, Medical University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany; Psychiatric Hospital, Friedrich-Ebert-Str, D-23774 Heiligenhafen, Germany; Institute of Immunology and Transfusion Medicine, Medical University of Leubeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany; Department of Neurology, Charite Campus Mitte, NWFZ 2680, R 04 023, Schumannstr 20/21, D-10117 Berlin, Germany
There has been a continuing discussion on the hypothesis that neurodegenerative mechanisms contribute to the etiopathogenesis of schizophrenia. Support for this hypothesis comes from postmortem studies and especially from recent volumetric MRI studies indicating that ventricular enlargement and hemispheric volumetric reductions may have a progressive component in patients with schizophrenia. Changes in brain structure and volume appear to arise from a reduction in neuritic processes (such as dendrites and synapses) rather than from a loss of neuronal or glial cell bodies. A missing link for this hypothesis is a biochemical marker for cellular integrity in the brain that can be measured during acute psychotic episodes of schizophrenic patients. S100B has the potential to be such a marker.
S100B, a calcium binding protein, is produced mainly by astroglial cells. It is involved in a variety of cellular mechanisms such as cellular proliferation and differentiation as well as the regulation of energy metabolism. Secreted in nanomolar concentrations, it promotes neuronal survival and regeneration. In micromolar concentrations, however, it is neurotoxic and induces the apoptosis of neurons and glial cells. In adult brains, it plays a role in neuronal plasticity and the long-term potentiation of learning processes.
S100B levels has been shown to increase after traumatic brain injury or toxic or ischemic brain damage as well as in multiple sclerosis and neurodegenerative disorders. Two independent studies have shown that acutely psychotic patients with schizophrenia have increased S100B levels.
After six weeks of treatment, one group of schizophrenic patients had S100B levels that returned to normal while a second group of patients continued to have increased levels. The patients of the second group had significantly higher PANSS negative scores than the first group, and the higher scores remained after six weeks of treatment. The increased S100B levels were associated with negative symptomatology. Amongst patients suffering from more severe negative symptoms, astroglial integrity may be affected to a greater degree not only in the acute stages of the disease but also after six weeks of treatment. A restoration of astroglial integrity seems to be associated with the improvement of negative symptoms.
In schizophrenia, severe negative symptoms often lead to an unfavorable clinical outcome. Besides affective and social impairment, cognitive deficits are major factors in determining adverse outcomes. Findings reporting a possible influence of cellular integrity (as indicated by S100B plasma levels) on cognitive function are therefore of special interest. In neuropsychological testing, minor head injury patients with elevated S100 levels showed disrupted reaction time, attention and speed of information processing. In head injury or stroke patients, a higher S100 plasma concentration predicted a more unfavorable clinical outcome compared to patients with lower S100 levels. Transgenic mice with an overproduction of S100B showed significant learning deficits and behavioral problems similar to mice with manifestations of hippocampal dysfunction.
Citation source: Molecular Psychiatry 2001 Volume 6, number 4, pages 445-449.
For further information on this work, please contact Dr. Matthias Rothermundt, Department of Psychiatry, University of Muenster, Albert-Schweitzer-Str. 11 D-48129 Muenster, Germany; Tel: 49-251-83-52581; Fax: 49-251-83-56612; Email: email@example.com
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