dc.contributor.author
Müller, Daniel J.
dc.date.accessioned
2018-06-07T17:41:23Z
dc.date.available
2008-11-20T08:23:24.085Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/4136
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-8336
dc.description.abstract
Zur Response untersuchten wir den Einfluss der Polymorphismen des SNAP-25, des
TNF-alpha- und des GNB3-Gens und fokussierten uns dabei auf symptombezogene
Analysen. Hierbei fand sich unter anderem ein signifikanter Befund des 825C/T
Polymorphismus des GNB3-Gens, der insbesondere mit Besserung positiver
Symptome assoziiert gewesen ist. Die hier vorgelegten Arbeiten sind als
Stimulus für Replikationsstudien geeignet, die bei komplex vererbten
Phänotypen von essentieller Bedeutung sind. Des Weiteren dienen die Studien
dazu, wichtige methodologische Prinzipien der Pharmakogenetik aufzuzeigen um
die gewonnenen Erkenntnisse in zukünftige Studien einfließen lassen zu können.
Durch die zurzeit auch in unserer Klinik laufenden Erstellung größerer und
prospektiv erfasster Kollektive sind weiterführende und wichtige Ergebnisse zu
erwarten. Durch Berücksichtigung genetischer Faktoren ist der Weg zu einer
wirkungsvolleren und nebenwirkungsärmeren Therapie inzwischen gebahnt worden.
Die Fiktion einer individualisierten Therapie kann in naher Zukunft zur
Realität werden und Pharmakogenetik ein fester Bestandteil der klinischen
Praxis sein.
de
dc.description.abstract
Studies and research summarized in this thesis have led to new insights that
aim to a achieve an individualized pharmacological therapy of schizophrenia
that is based on pharmacogenetics. In particular, these studies have been
focussing on side effects (tardive dyskinesia and weight change) and response
to antipsychotics. The first study has included family members of
schizophrenic individuals and has demonstrated a genetic component in the
incidence of tardive dyskinesia. In molecular genetic based studies, however,
no particular associations between tardive dyskinesia and CYP2D6 gene variants
were found, although various clinical and demographic factors were included to
correct for potential confounders. In contrast, in a later study, a
significant association between the functional relevant 759 C/T polymorphism
of the DRD2 gene with tardive dyskinesia could be detected. In a further pilot
study, focussing on the Pro179Leu polymorphism of the GPX1-gene and tardive
dyskinesia, no significant association has been detected. Regarding
antipsychotic induced weight gain, the influence of the 957C/T promoter
polymorphism of the 5-HT2C gene has been investigated for the first time by
doing a meta-analysis. Despite a significant heterogeneity across studies, a
significant association could be detected. The SNAP-25 gene has been analysed
for the first time where two polymorphisms (MnlI, TaiI) were found to be
associated with weight gain and response, although a significant relationship
with other co-factors has also been detected. Finally, we investigated the
G-308A polymorphism of the TNF-alpha gene and found a non-significant trend
with weight gain induced by antipsychotics. Analyses on the SNAP-25, TNF-alpha
and GNB3 genes then also focussed on specific schizophrenia related symptoms.
Here, a significant association between the 825C/T polymorphism of the
GNB3-gene and improvement in positive symptoms has been observed. The studies
presented here may serve as stimulus for replication studies, which are of
utmost importance in complex inherited phenotypes such as outcome to
antipsychotic drugs. Furthermore, these studies may also serve to illustrate
important methodological principles in pharmacogenetics. Individualized
therapy does not have to remain a fiction but is likely to become a reality
soon. Pharmacogenetics is on its way to become a common and indispensable tool
in clinical practice.
en
dc.rights.uri
http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen
dc.subject
Pharmacogenetics
dc.subject
tardive dyskinesia
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Genetische Faktoren in der pharmakologischen Behandlung der Schizophrenie
dc.contributor.contact
daniel.mueller@charite.de
dc.contributor.firstReferee
Prof. Dr. med. J. Deckert
dc.contributor.furtherReferee
Prof. Dr. med. H. J. Möller
dc.date.accepted
2008-05-19
dc.identifier.urn
urn:nbn:de:kobv:188-fudissthesis000000006041-4
dc.title.translated
Genetic factors in the pharmacological treatment of schizophrenia
en
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDISS_thesis_000000006041
refubium.mycore.derivateId
FUDISS_derivate_000000011306
dcterms.accessRights.dnb
free
dcterms.accessRights.openaire
open access