Störungen im Phospholipidmetabolismus als mögliche pathogenetische Faktoren der Schizophrenie

Zusammenfassung:

Seit einigen Jahren wird der Lipidstoffwechsel schizophrener Patienten anhand von Enzymanalysen und Bestimmungen von Membransynthese- bzw. -abbaustoffen untersucht. Bisher wurden hierzu sowohl Messungen an Blutproben als auch an verschiedenen Zellpopulationen durchgeführt. In Analogie dazu lassen sich mittels neuerer Untersuchungsverfahren, wie der ³¹P-Magnetresonanz-Spektroskopie (³¹P-MRS), auch nichtinvasiv in vivo derartige Membranstoffwechselparameter bestimmen.

Im Rahmen der Membranphospholipid-Hypothese der Schizophrenie werden Arachidonsäuredefizite peripherer Zellmembranen, Phosphodiesterturnover im Gehirn, Phospholipase A₂ (PLA₂)-Aktivitätssteigerung im Serum und in Blutzellen, verminderte Niacin-Sensibilität und Abnormitäten des PLA₂-Gens bei Schizophrenen diskutiert. Dennoch sind die Zusammenhänge zwischen diesen und psychopathologischen Befunden bisher spekulativ. Außerdem ist es notwendig, die Übertragbarkeit der peripheren Messergebnisse auf den Stoffwechsel im zentralen Nervensystem (ZNS) selbst zu belegen.

Ausgehend von nicht neuronalen Enzym- und Stoffwechselanalysen anderer Arbeitsgruppen sollen aktuelle Ergebnisse im Zusammenhang mit eigenen ³¹P-MR-spektroskopischen Arbeiten zusammenfassend dargestellt werden, um Übereinstimmungen und Zusammenhänge zwischen zentralen und peripheren Untersuchungstechniken aufzuzeigen und neue Therapieansätze für die Schizophrenie zu eruieren.

Disturbances of Phospholipidmetabolism - Possible Pathogenic Factors in Schizophrenia. Survey and Discussion of Current Findings:

During the last few years analyses of the lipidmetabolism have been performed on schizophrenic patients. Anabolic and katabolic metabolite-concentrations from blood and cell samples have been measured. By means of new investigation techniques, such as ³¹P-magnetic-resonance-spectroscopy, it is nowadays even possible to determine membrane metabolites non-invasively in vivo.

Arachidonic acid deficits in peripheral cell membranes, turnover of phosphodiesters in the brain, increased phospholipase A₂ (PLA₂)-activity in serum and blood cells, disturbed niacin-response and abnormalities of the PLA₂-gene are summarised as phospholipid-membrane-hypothesis of schizophrenia. Although there is some evidence for correlations between those findings and psychotic symptoms, the connection to the pathogenesis of schizophrenia still has speculative character. Furthermore it has to be confirmed that peripheral biochemical findings acquired in schizophrenics are transferable to the metabolism of the central nervous system.

Actual results of enzyme and metabolite measurements reported in literature and current findings of our own ³¹P-MR-spectroscopic studies are surveyed and summarised. To point out possible connections between the phospholipid-metabolism of the central nervous system and of peripheral blood-cells, systemic approaches are considered.

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