dc.contributor.advisor | Gruber, Oliver Prof. Dr. | de |
dc.contributor.author | Platz, Birgit | de |
dc.date.accessioned | 2013-01-14T15:31:46Z | de |
dc.date.available | 2013-01-30T23:51:06Z | de |
dc.date.issued | 2012-09-28 | de |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-000D-F010-5 | de |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-1617 | |
dc.description.abstract | Die | de |
dc.format.mimetype | application/pdf | de |
dc.language.iso | ger | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | de |
dc.title | Eine Voxel-basierte morphometrische Untersuchung der Effekte von Suszeptibilitätsgenen der Schizophrenie auf hirnregionale Volumina der grauen Substanz | de |
dc.type | doctoralThesis | de |
dc.title.translated | A voxel-based morphometric study about the effects of susceptibility genes for schizophrenia on grey matter volumes | de |
dc.contributor.referee | Gruber, Oliver Prof. Dr. | de |
dc.date.examination | 2012-10-08 | de |
dc.subject.dnb | 610 Medizin, Gesundheit | de |
dc.subject.gok | MED 540 | de |
dc.description.abstracteng | The etiology of schizophrenia and other
psychiatric disorders is characterized by a strong genetic
influence which was confirmed in family, twin and adoption studies.
Within genome wide coupling and association studies certain
chromosomal regions with an increased risk for psychiatric
diseases, in particular for schizophrenia, could be discovered,
such as the susceptibility genes DTNBP-1, NRG-1, DISC-1 and G72.
Certain allelic variations of these genes, so-called SNP (single
nucleotide polymorphisms), are associated with an increased risk
for the disorder.
These susceptibility genes are believed to influence brain regional
volumes of grey matter. Hippocampal volume reduction is one of the
major neuropathological findings in schizophrenia. Further
so-called endophenotypes are reduced volume of temporal lobes,
frontal lobes, ventrolateral prefrontal cortex (VLPFC) as well as
dorsolateral prefrontal cortex (DLPFC).
In the present study 161 patients with schizophrenia (n= 44),
bipolar disorder (n= 42), compulsive disorder (n= 31) as well as a
healthy control group (n= 44) were examined. All study participants
were genotyped with respect to the single nucleotide polymorphisms
and submitted to imaging of T1-weighted MRI on a 1,5 Tesla system.
The analysis of the images was carried out using voxel-based
morphometry (VBM). The statistical evaluation was based on SPM5
(statistical parametric mapping).
According to the previous findings, structural changes of grey
matter were found in region of hippocampus, frontal and temporal
lobes and other structures. Interestingly, the risk SNP of all
examined susceptibility genes showed an increased grey matter
volume instead of volume deficits.
In DTNBP-1 the SNP rs2619522 (P1763) with the risk allele guanine
and the SNP rs1018381 (P1578) with the allele thymine were
examined. In both gene variants, volume alterations were found in
the left hippocampus, the frontal and temporal cortex. Effects of
frontal and temporal increased grey matter volumes were found in
the SNP rs4733263 of the risk gene NRG-1 with respect to the
guanine variant. The risk allele adenine encoding for the amino
acid serine in the SNP rs821616 (exon11 / ser704cys) of the DISC-1
is responsible for alterations of the frontal and temporal cortex.
The risk gene G72 with regard to the SNP rs1935058 and the cytosine
variant is associated with grey matter changes in area of left
hippocampus, frontal and temporal lobe. With respect of the SNP
rs778294 (M19) an increased grey matter volume in the region of
frontal and temporal lobe can be found in carriers of the risk
allele thymine.
In contrast to prior findings this study shows an increase of grey
matter volume. While this might be compensatory due to disturbed
feedback-loops, it could also reflect a relative volume increase
due to a mismatch between grey and white matter. Chronic
neuroleptic medication has also been described to cause this
effect. It seems likely that the multifactorial etiology of
schizophrenia with its genetic heterogeneity is reflected in a
large variety of phenotypes- not only with regard to clinical
presentation but also in terms of morphologic alterations at the
CNS level. | de |
dc.contributor.coReferee | Dechent, Peter PD Dr. | de |
dc.contributor.thirdReferee | Virsik-Köpp, Patricia Prof. Dr. | de |
dc.subject.topic | Medicine | de |
dc.subject.ger | Suszeptibilitätsgene | de |
dc.subject.ger | SNP | de |
dc.subject.ger | DTNBP-1 rs2619522 rs1018381 | de |
dc.subject.ger | NRG-1 rs4733263 | de |
dc.subject.ger | DISC-1 rs821616 rs6675281 | de |
dc.subject.ger | G72 rs778294 rs1935058 | de |
dc.subject.ger | MRT | de |
dc.subject.ger | VBM | de |
dc.subject.ger | Endophänotyp | de |
dc.subject.ger | Schizophrenie | de |
dc.subject.ger | Imaging Genetics | de |
dc.subject.ger | Hippokampus | de |
dc.subject.eng | susceptibility genes | de |
dc.subject.eng | single nucleotide polymorphism | de |
dc.subject.eng | DTNBP-1 rs2619522 rs1018381 | de |
dc.subject.eng | NRG-1 rs4733263 | de |
dc.subject.eng | DISC-1 rs821616 rs6675281 | de |
dc.subject.eng | G72 rs778294 rs1935058 | de |
dc.subject.eng | MRI | de |
dc.subject.eng | VBM | de |
dc.subject.eng | schizophrenia | de |
dc.subject.eng | imaging genetics | de |
dc.subject.bk | 44.91 | de |
dc.identifier.urn | urn:nbn:de:gbv:7-webdoc-3721-4 | de |
dc.identifier.purl | webdoc-3721 | de |
dc.affiliation.institute | Medizinische Fakultät | de |
dc.identifier.ppn | 731820754 | de |