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Cloettapreis_2013_Nr_41

27 ­interpreted as compensatory activity to achieve the same level of per­ formance as the genotype group with high memory performance23 . Inter- pretation becomes difficult if the fMRI study reveals genotype-dependent activity differences despite non-significant differences in memory per- formance in genotype groups unmatched for performance. This situation is common, because the number of subjects used in imaging genetic ­studies reporting significant genotype-dependent differences in brain ac- tivity typically lay between 20 and 60 subjects, whereas behavioral ge- netics studies usually used hundreds or thousands of subjects to con- sistently produce significant results54 . A possible explanation for this observation is that neural activity is more proximate to the direct effects of functional genetic polymorphisms on gene products and their func- tion, and might therefore be more sensitive in estimating genotype-de- pendent differences in mental processing54, 56, 57 . Nevertheless, genotype- dependent differences in brain activity that do not translate to significant differences in behavior should be interpreted with caution. From gene hunting to drug discovery As highlighted above, the recent advances in human genetics have led to an unprecedented rate of discovery of genes related to complex human disease, including neuropsychiatric disorders58-60 . The human genome- based gain of knowledge is certainly expected to have a large impact on drug discovery in complex human disease61-63 . It is, however, still not clear to what extent this knowledge can be used as a starting point for the iden- tification of druggable molecular pathways of complex traits, including mental disorders. Very recently, we focused on emotionally aversive epi- sodic memory – a trait central to anxiety disorders such as posttraumatic stress disorder (PTSD). Strong memory for emotionally arousing events can be seen as a primarily adaptive phenomenon, which helps us to re- member vital information (e.g. dangerous situations). In case of an ex­ tremely aversive event, however, this mechanism can also lead to intru­ sive and persistent traumatic memories, thereby contributing to the development and symptoms of PTSD. Symptoms related to aversive ­memory include intrusive daytime recollections, traumatic nightmares and flashbacks in which components of the event are relived. Aversive memory is a genetically complex trait as shown both in healthy subjects

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