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Nervenheilkunde 2006; 25(01/02): 28-31
DOI: 10.1055/s-0038-1626436
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Molekulare Grundlagen der Schizophrenie

Der 5-HT2A-RezeptorMolecular principles of schizophreniaThe 5-HT2A-receptor
R. Hurlemann
1   Brain Imaging Center West, Institut für Medizin, Forschungszentrum Jülich
2   Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Bonn
,
A. Bauer
1   Brain Imaging Center West, Institut für Medizin, Forschungszentrum Jülich
,
K. Vogeley
3   Klinik für Psychiatrie und Psychotherapie des Klinikums der Universität zu Köln
,
P. Falkai
4   Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum des Saarlandes, Homburg/Saar
,
M. Wagner
2   Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Bonn
,
W. Maier
2   Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Bonn
› Author Affiliations
Further Information

Publication History

Publication Date:
22 January 2018 (online)

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Zusammenfassung

Der Serotonin2A-Rezeptor (5-HT2AR) wird sowohl mit der Pathologie der Schizophrenie als auch mit dem Wirkungsmechanismus vieler atypischer Antipsychotika in Verbindung gebracht. Da atypische Antipsychotika wie Clozapin den 5-HT2AR blockieren und die 5-HT2AR-Dichte reduzieren, stellt sich die Frage, ob die in Post-mortem-Untersuchungen schizophrener Patienten festgestellte Abnahme der 5-HT2AR-Dichte ein Indikator der zu Grunde liegenden Erkrankung oder ein sekundärer medikamentöser Effekt ist. Zur Klärung dieser Frage sind Studien über den In-vivo-Status des 5-HT2AR bei der Schizophrenie erforderlich, die vor Erstmanifestation der Erkrankung und vor Beginn einer pharmakologischen Therapie durchgeführt werden. Dieser Überlegung trägt unsere Pilotstudie Rechnung, bei der unter Verwendung des Radioliganden [18F]Altanserin und der Positronenemissionstomographie (PET) Verminderungen der 5-HT2AR-Verfügbarkeit im orbitofrontalen und dorsolateralen präfrontalen Kortex bei Patienten mit Symptomen psychosenaher und psychoseferner Prodromalzustände der Schizophrenie festgestellt wurden. Diese Ergebnisse sprechen für eine erkrankungsbedingte serotonerge Dysregulation in Hirnarealen, deren frühe Störung an der Entstehung affektiver und kognitiver Symptome der Schizophrenie beteiligt sein könnte.

Summary

The brain serotonin2A receptor (5-HT2AR) has been implicated in both the pathology of schizophrenia and the therapeutic action of many atypical antipsychotics. As atypical antipsychotics like clozapine antagonize the 5-HT2AR and reduce 5-HT2AR density, it cannot be ruled out that a prefrontal decrease of 5-HT2AR density observed in postmortem brains from patients with schizophrenia is triggered by antipsychotic drug effects. Today, little is known about the 5-HT2AR in vivo status before the first psychotic episode and before the exposure to antipsychotics. Into this void comes our pilot study in which we used the radioligand [18F]altanserin and positron emission tomography (PET) to investigate individuals at increased risk of developing schizophrenia. We identified decreases of 5-HT2AR availability in orbitofrontal cortex and dorsolateral prefrontal cortex, suggesting that disease-related abnormalities of serotonergic neurotransmission emerge in brain areas involved in affective and cognitive processes, dysfunctions of which are core representations of the schizophrenic phenotype.

Schlüsselwörter

Schizophrenie - Prodrom - PET - Serotonin - 5-HT2A-Rezeptor

Keywords

Schizophrenia - at-risk mental state - PET - serotonin - 5-HT2A-receptor
 

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