title: Human genome-guided identification of memory-modulating drugs.
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.
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: Christiane
authors.initials: C
authors.lastname: Gerhards
authors.forename: Angela
authors.initials: A
authors.lastname: Heck
authors.forename: Sandra
authors.initials: S
authors.lastname: Ackermann
authors.forename: Amanda
authors.initials: A
authors.lastname: Aerni
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schicktanz
authors.forename: Bianca
authors.initials: B
authors.lastname: Auschra
authors.forename: Philippe
authors.initials: P
authors.lastname: Demougin
authors.forename: Eva
authors.initials: E
authors.lastname: Mumme
authors.forename: Thomas
authors.initials: T
authors.lastname: Elbert
authors.forename: Verena
authors.initials: V
authors.lastname: Ertl
authors.forename: Leo
authors.initials: L
authors.lastname: Gschwind
authors.forename: Edveena
authors.initials: E
authors.lastname: Hanser
authors.forename: Kim-Dung
authors.initials: KD
authors.lastname: Huynh
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Iris-Tatjana
authors.initials: IT
authors.lastname: Kolassa
authors.forename: Annette
authors.initials: A
authors.lastname: Milnik
authors.forename: Paolo
authors.initials: P
authors.lastname: Paganetti
authors.forename: Klara
authors.initials: K
authors.lastname: Spalek
authors.forename: Christian
authors.initials: C
authors.lastname: Vogler
authors.forename: Andreas
authors.initials: A
authors.lastname: Muhs
authors.forename: Andrea
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Dominique J-F
authors.initials: DJ
authors.lastname: de Quervain
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D057225:Data Mining / Q000379:methods; D004155:Diphenhydramine / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D005260:Female; D005470:Fluorometry; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007407:Interviews as Topic; D016015:Logistic Models; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009841:Oligonucleotides / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000235:genetics*; D017741:Survivors / Q000523:psychology*; D013557:Switzerland; D055815:Young Adult
chemical_list: D009841:Oligonucleotides; D004155:Diphenhydramine
keywords: PTSD; emotional memory; pharmacology