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Human genome-guided identification of memory-modulating drugs

Papassotiropoulos, Andreas and Gerhards, Christiane and Heck, Angela and Ackermann, Sandra and Aerni, Amanda and Schicktanz, Nathalie and Auschra, Bianca and Demougin, Philippe and Mumme, Eva and Elbert, Thomas and Ertl, Verena and Gschwind, Leo and Hanser, Edveena and Huynh, Kim-Dung and Jessen, Frank and Kolassa, Iris-Tatjana and Milnik, Annette and Paganetti, Paolo and Spalek, Klara and Vogler, Christian and Muhs, Andreas and Pfeifer, Andrea and de Quervain, Dominique J.-F.. (2013) Human genome-guided identification of memory-modulating drugs. Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, H. 46 , E4369-E4374.

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Official URL: http://edoc.unibas.ch/dok/A6211978

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Abstract

In the last decade there has been an exponential increase in knowledge about the genetic basis of complex human traits, including neuropsychiatric disorders. It is not clear, however, to what extent this knowledge can be used as a starting point for drug identification, one of the central hopes of the human genome project. The aim of the present study was to identify memory-modulating compounds through the use of human genetic information. We performed a multinational collaborative study, which included assessment of aversive memory - a trait central to posttraumatic stress disorder - and a gene-set analysis in healthy individuals. We identified 20 potential drug target genes in two genomewide-corrected gene sets: the neuroactive ligand-receptor interaction and the long-term depression gene set. In a subsequent double-blind, placebo-controlled study in healthy volunteers, we aimed at providing a proof of concept for the genome-guided identification of memory modulating compounds. Pharmacological intervention at the neuroactive ligand-receptor interaction gene set led to significant reduction of aversive memory. The findings demonstrate that genome information, along with appropriate data mining methodology, can be used as a starting point for the identification of memory-modulating compounds.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:Vogler, Christian and Gerhards, Christiane and Papassotiropoulos, Andreas and Heck, Angela and Aerni, Amanda and Schicktanz, Nathalie and Auschra, Bianca and Demougin, Philippe and Gschwind, Leo and Hanser, Edveena and Huynh, Kim-Dung and Milnik, Annette and Sifalakis, Klara and de Quervain, Dominique J.-F.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Nov 2014 08:29
Deposited On:27 Mar 2014 13:13

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