Zusammenfassung
Der Schwerpunkt dieser Übersichtsarbeit liegt in der funktionellen Bildgebung mit der funktionellen Magnetresonanztomographie (FMRT), Positronenemissionstomographie (PET) und SPECT. Neue die „Dopaminhypothese der Schizophrenie” stützende Hinweise werden zusammengefasst, einschließlich Veränderungen des präsynaptischen dopaminergen Metabolismus und des postsynaptischen Rezeptorbindungspotentials. Resultate von dopaminergen Provokationsstudien mit Amphetamin und AMPT werden dargestellt. Mehrere PET und SPECT-Studien zeigten einen deutlichen Anstieg der Amphetamin-induzierten Dopaminausschüttung und der AMPT-induzierten Dopamindepletion in medikamenten-naiven Patienten und weisen auf eine Dysregulation der dopaminergen Neurotransmission hin. Provokationsstudien mit Amphetamin und dem NMDA-Rezeptor-Antagonisten Ketamin werden zu der glutaminergen Dysfunktion und der Wechselwirkung mehrerer Neurotransmitter in Beziehung gesetzt. Die aufgabenspezifische funktionelle Konnektivität gemessen mit fMRT und PET wird unter besonderer Berücksichtung des präfrontalen Kortex und temporaler Strukturen diskutiert. Ein Anstieg des Serotonin-1A-Rezeptorbindungspotenzials im präfrontalen und mesotemporalen Kortex wird auf die Interaktion zwischen dopaminergem und serotonergem System bezogen. Genetisches Neuroimaging mit Voxel-basierter Morphometrie (VBM) und fMRT zeigte signifikante Effekte des Dopamin-metabolisierenden Enyzms COMT auf die funktionelle Aktivität des präfrontalen Kortex. Funktionelles Neuroimaging basierend auf Provokationsparadigmen im PET als auch auf aufgabenspezifischen Veränderungen der fMRT-Aktivierungsmuster scheint ein vielversprechender Kandidat für die Entwicklung von biologischen Markertests für schizophrene Erkrankungen zu sein.
Abstract
This overview is focused on functional neuroimaging including functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT). Recent evidence for the “dopamine hypothesis of schizophrenia” is summarized including alterations of presynaptic dopamine metabolism and postsynaptic receptor binding potential. Emphasis is given to dopaminergic challenge studies using amphetamine and AMPT. Several PET and SPECT studies have shown a pronounced increase of amphetamine-induced dopamine release as well as decrease of AMPT-induced dopamine depletion in drug-naive schizophrenic patients, indicating a dysregulation of dopaminergic neurotransmission. Results of studies combining amphetamine challenge and the NMDA receptor antagonist ketamine are related to glutaminergic dysfunction and neurotransmitter interactions. FMRI and PET results demonstrating alterations in task-specific functional connectivity between brain areas are discussed with a focus on the prefrontal cortex and temporal structures. Increase of serotonin-1A receptor binding potential in prefrontal and mesotemporal cortex is related to the serotonin-dopamine interaction. Genetic neuroimaging techniques, including voxel-based morphometry (VBM) and fMRI, revealing significant effects of the dopamine metabolizing enzyme COMT on functional activation in prefrontal areas are also discussed. Functional neuroimaging based on challenge-paradigms in PET as well as task-specific state- or trait-dependent alterations of activation patterns in fMRI, seems to be a promising candidate for the development of biological marker tests for schizophrenia.
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O. Univ. Prof. Dr. h. c. Dr. Siegfried Kasper
Klinische Abteilung für Allgemeine Psychiatrie · Medizinische Universität Wien
Währinger Gürtel 18-20
1090 Wien
Österreich
Email: sci-genpsy@meduniwien.ac.at
