Human genome-guided identification of memory-modulating drugs.
Author(s): Papassotiropoulos A(1), Gerhards C, Heck A, Ackermann S, Aerni A, Schicktanz N,
Auschra B, Demougin P, Mumme E, Elbert T, Ertl V, Gschwind L, Hanser E, Huynh KD,
Jessen F, Kolassa IT, Milnik A, Paganetti P, Spalek K, Vogler C, Muhs A, Pfeifer
A, de Quervain DJ.
Affiliation(s): Author information:
(1)Department of Psychology, Division of Molecular Neuroscience, Psychiatric
University Clinics, Transfaculty Research Platform, Department Biozentrum, Life
Sciences Training Facility, and Department of Psychology, Division of Cognitive
Neuroscience, University of Basel, 4055 Basel, Switzerland.
Publication date & source: 2013, Proc Natl Acad Sci U S A. , 110(46):E4369-74
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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