uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Decrease of serotonin receptor 2C in schizophrenia brains identified by high-resolution mRNA expression analysis
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Evolutionary Biology. (Behavioral Genetics)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. (Behavioral Genetics)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. (Behavioral Genetics)
2003 (English)In: Biological Psychiatry, ISSN 0006-3223, Vol. 54, no 11, 1212-1221 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: RNA expression profiling can provide hints for the selection of candidate susceptibility genes, for formulation of hypotheses about the development of a disease, and/or for selection of candidate gene targets for novel drug development. We measured messenger RNA expression levels of 16 candidate genes in brain samples from 55 schizophrenia patients and 55 controls. This is the largest sample so far used to identify genes differentially expressed in schizophrenia brains. METHODS: We used a sensitive real-time polymerase chain reaction methodology and a novel statistical approach, including the development of a linear model of analysis of covariance type. RESULTS: We found two genes differentially expressed: monoamine oxidase B was significantly increased in schizophrenia brain (p =.001), whereas one of the serotonin receptor genes, serotonin receptor 2C, was significantly decreased (p =.001). Other genes, previously proposed to be differentially expressed in schizophrenia brain, were invariant in our analysis. CONCLUSIONS:The differential expression of serotonin receptor 2C is particularly relevant for the development of new atypical antipsychotic drugs. The strategy presented here is useful to evaluate hypothesizes for the development of the disease proposed by other investigators.

Place, publisher, year, edition, pages
2003. Vol. 54, no 11, 1212-1221 p.
National Category
Physiology Genetics
Identifiers
URN: urn:nbn:se:uu:diva-90902DOI: 10.1016/S0006-3223(03)00526-2OAI: oai:DiVA.org:uu-90902DiVA: diva2:163419
Available from: 2003-10-14 Created: 2003-10-14 Last updated: 2010-02-02Bibliographically approved
In thesis
1. High-resolution Studies of mRNA Expression in Brain: A Search for Genes Differently Expressed in Schizophrenia
Open this publication in new window or tab >>High-resolution Studies of mRNA Expression in Brain: A Search for Genes Differently Expressed in Schizophrenia
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gene expression differences between patients and controls can be used to find susceptibility genes and drug targets for a disease. High-resolution strategies are required because the differences between the investigated groups may be small and numerous factors may affect the mRNA quantity. This thesis is based on the use of real-time RT-PCR combined with a new statistical approach, developed to detect small differences between patients and controls and differences due to patient subgroups.

Comparisons between human brain biopsy and autopsy samples showed that post-mortem tissue can be used to make conclusions on the relative mRNA levels in the living brain.

Power analysis based on human brain mRNA expression from 14 genes adjusted with two reference genes, revealed that a sample size of 50 patients and 50 controls was required to detect a 2-fold difference with a power and a confidence of 95%. A similar study in rats revealed that approximately the same sample size was required for rat brain mRNA expression studies.

The mRNA levels of several genes were studied in 55 schizophrenia and 55 control prefrontal brain autopsies, using a novel and more powerful statistical analysis. The serotonin receptor 2C gene (HTR2C) showed a significant 1.5-fold decrease in the patients as compared to controls, and the monoamine oxidase B gene (MAOB) a 1.2-fold increase.

The mechanism behind the decrease of HTR2C mRNA levels was investigated by studying the correlation of drug treatment and HTR2C promoter polymorphisms to the HTR2C expression levels. The observed decrease was present in untreated patients, suggesting that the HTR2C mRNA decrease is correlated with the disease and not the treatment. There was no association between promoter polymorphisms and HTR2C expression levels. Thus, the molecular mechanism for the decreased expression remains unclear. Nevertheless, the results support a role for monoaminergic synapses in schizophrenia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 47 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 894
Keyword
Genetics, mRNA, gene expression, real-time RT-PCR, schizophrenia, 5-HT (serotonin) receptor 2C, brain, psychiatric genetics, Genetik
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-3605 (URN)91-554-5755-X (ISBN)
Public defence
2003-11-07, Lindahlsalen, EBC, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2003-10-14 Created: 2003-10-14 Last updated: 2010-02-08Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text
By organisation
Evolutionary BiologyEvolutionary Biology
In the same journal
Biological Psychiatry
PhysiologyGenetics

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 598 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf