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Cloettapreis_2013_Nr_41

28 and in traumatized individuals50, 64 . Furthermore, we recently reported evidence suggesting a genetic link between the predisposition to build strong aversive memories and the risk for PTSD64 . Based on these observations, we decided to perform a multinational col- laborative study, which included assessment of aversive memory and a gene-set analysis in healthy individuals. We identified 20 potential drug target genes in 2 genome-wide corrected gene sets, the neuroactive li- gand-receptor interaction and the long-term depression gene set. In a sub- sequent double-blind, placebo-controlled study in healthy volunteers we aimed at providing a proof-of-concept for the genome-guided identifica- tion of memory modulating compounds. Pharmacological intervention at the neuroactive ligand-receptor interaction gene set led to significant reduction of aversive memory. This recent study demonstrated that ge- nome information, along with appropriate data mining methodology, can be used as a starting point for the identification of memory-modulating compounds65 . Concluding remarks As with any genetically complex trait, neuroscientists focusing on the study of the genetic underpinnings of episodic memory have to deal with manifold complexity levels. First, the trait (i.e., episodic memory) per se represents an assembly of phenotypes with overlapping, but also par­- tially distinct molecular profiles. Secondly, complexity at the genetic le- vel is not only related to the polygenic nature of the trait itself, but it also reflects the complexity of the human genome, which exerts its influence on the trait not only through simple, linear gene effects, but also through gene-gene interactions, gene-environment interactions, and epigenetic mechanisms. Finally, the relation between genetic and phenotypic vari- ability is not expected to follow simple and general rules applicable to every memory-related phenotype. Despite this obvious complexity, empirical evidence supports the notion that behavioral genetic studies of episodic memory successfully identify trait-associated molecules and pathways. As new technological and ana- lytical approaches – both at the genetic and the phenotypic level – emer- ge, two simple and important pillars of reliable genetic research must not be forgotten: Firstly, regardless of the statistical models used and how-

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