Human genome-guided identification of memory-modulating drugs

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2013
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Papassotiropoulos, Andreas
Gerhards, Christiane
Heck, Angela
Ackermann, Sandra
Aerni, Amanda
Schicktanz, Nathalie
Auschra, Bianca
Demougin, Philippe
Mumme, Eva
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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.

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Fachgebiet (DDC)
150 Psychologie
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emotional memory, pharmacology, PTSD
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ISO 690PAPASSOTIROPOULOS, Andreas, Christiane GERHARDS, Angela HECK, Sandra ACKERMANN, Amanda AERNI, Nathalie SCHICKTANZ, Bianca AUSCHRA, Philippe DEMOUGIN, Eva MUMME, Thomas ELBERT, Verena ERTL, Leo GSCHWIND, Edveena HANSER, Kim-Dung HUYNH, Frank JESSEN, Iris-Tatjana KOLASSA, Annette MILNIK, Paolo PAGANETTI, Klara SPALEK, Christian VOGLER, Andreas MUHS, Andrea PFEIFER, Dominique J.-F. DE QUERVAIN, 2013. Human genome-guided identification of memory-modulating drugs. In: Proceedings of the National Academy of Sciences of the United States of America. 2013, 110(46), pp. E4369-E4374. ISSN 0027-8424. eISSN 1091-6490
BibTex
@article{Papassotiropoulos2013Human-26195,
  year={2013},
  title={Human genome-guided identification of memory-modulating drugs},
  url={http://dx.doi.org/    10.1073/pnas.1314478110},
  number={46},
  volume={110},
  issn={0027-8424},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  pages={E4369--E4374},
  author={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.}
}
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