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Fortschr Neurol Psychiatr 2001; 69(11): 503-509
DOI: 10.1055/s-2001-18379
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Antipsychotika und Phospholipidmetabolismus bei der Schizophrenie

Antipsychotics and Phospholipid Metabolism in SchizophreniaA.  Schmitt1 , A.  Maras1 , D.  F.  Braus1 , G.  Petroianu2 , A.  Jatzko1 , W.  F.  Gattaz3
  • 1 1Zentralinstitut für Seelische Gesundheit, Mannheim (Direktor: Prof. Dr. Dr. F. A. Henn)
  • 2 2Institut für Pharmakologie und Toxikologie, Mannheim (Direktor: Prof. Dr. B. Lemmer)
  • 3 3Department of Psychiatry, Faculty of Medicine, University of Sao Paulo/Brazil (Direktor: Prof. Dr. W. F. Gattaz)
Die Arbeit wurde unterstützt durch die Deutsche Forschungsgemeinschaft, SFB 258, S4.
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Publication History

Publication Date:
12 November 2001 (online)

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Zusammenfassung

An peripheren Zellen, in Post-mortem-Gehirnuntersuchungen und mittels der In-vivo-31P-Magnetresonanz-Spektroskopie (MRS) wurde wiederholt eine Beschleunigung des Phospholipidmetabolismus bei schizophrenen Patienten beschrieben. Die Spezifität der Ergebnisse für die Schizophrenie und der Einfluss antipsychotischer Medikation wurde bislang nicht hinreichend untersucht. In der vorliegenden Studie wurde die Zusammensetzung der Membranphospholipide an Thrombozyten bei 67 unbehandelten schizophrenen Patienten im Vergleich zu gesunden und psychiatrischen Kontrollen bestimmt. Bei einer Subgruppe der Patienten wurden die Effekte einer 6-monatigen antipsychotischen Behandlung auf den Phospholipidmetabolismus untersucht. Während bei unbehandelten Patienten die Hauptbestandteile der Membranphospholipide, Phosphatidylcholin und Phosphatidylethanolamin im Vergleich zu den Kontrollen erniedrigt und deren durch Aktivität der Phospholipase A2 entstandenes Abbauprodukt Lysophosphatidylcholin (LPC) erhöht war, sank LPC während einer 3-wöchigen, standardisierten Haloperidol-Therapie signifikant ab. Im Langzeitverlauf, bei Verwendung klassischer und atypischer Antipsychotika finden sich divergente Effekte. So blieb LPC unter kontinuierlicher Therapie mit typischen Neuroleptika weiterhin erniedrigt, während es bei denjenigen Patienten, die auf das Atypikum Zotepin umgestellt wurden, zu einem Anstieg von LPC kam. Unterschiedliche Wirkungen verschiedener Substanzklassen der Antipsychotika auf den Phospholipidmetabolismus können möglicherweise die divergenten Befunde der 31P-MRS bei medizierten schizophrenen Patienten erklären.

Abstract

To date numerous in-vivo 31P-MRS and in-vitro studies in schizophrenic patients have been able to demonstrate changes in their membrane phospholipid metabolism, which might be relevant for the cause and the therapeutic responsiveness of this disorder. Thus far, however, only limited studies exist regarding the specificity of these findings for schizophrenia and the effect of antipsychotic medication. The present study examined the composition of membrane phospholipids in platelets of 67 neuroleptic-free schizophrenic patients compared to healthy and psychiatric controls. In a subsample of the schizophrenic patients we determined the effect of antipsychotic treatment on the phospholipid metabolism during six-months follow up. While untreated patients showed a decrease in major membrane phospholipid components, i.e. phosphatidylcholine and phosphatidylethanolamine, when compared to control subjects, as well as an increase in their breakdown-product lysophosphatidylcholine (LPC), there was a significant reduction in LPC during three weeks of pharmacotherapy with haloperidol. After six months treatment with different antipsychotics some divergent effects on phospholipid metabolism in schizophrenic patients could be demonstrated. While in the long-term course LPC remained decreased under continuous therapy with typical neuroleptics, patients being treated with the atypical drug zotepine showed an increase in LPC compared to their baseline level before therapy. Thus, specific mechanisms of the different antipsychotic therapies on phospholipid metabolism might serve to explain the divergent findings of 31P-MRS in medicated patients.

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Dr. med. A. Schmitt

Zentralinstitut für Seelische Gesundheit, J5

68159 Mannheim

Email: schmitt@as200.zi-mannheim.de

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