Gen-Umwelt Interaktionen bei gesunden Probanden mit und ohne Kindheitstraumata und ihre subklinischen Persönlichkeitsausprägungen

It has been known for quite some time, that genetic and environmental factors interact with each other and have effects on human health. In particular, the widely researched gene variant CACNA1C rs1006737 plays an important role in the development of psychiatric diseases. In addition, in healthy subjects with the A-allele of the CACNA1C rs1006737 risk variant, abnormalities are found in functional MRI, which have different effects on memory function. Among other things, deficits in working memory become apparent here. The L-type Cav1.2 channel, encoded by the risk gene CACNA1C, also plays an essential role in synaptic plasticity, for learning and the working memory. It is also known that the environmental factor “childhood trauma” has an impact on mental health and is associated with the development of affective disorders. Neuropsychological deficits in memory and executive functions, as well as behavioral neuropsychological abnormalities are also found in connection with childhood trauma. Both risk factors also show behavioral neuropsychological abnormalities. The A-allele of the CACNA1C rs1006737 risk variant is associated with a reduced preference for social activities, anxiety and sex-specific differences in emotional lability and resilience. Neglected children showed fewer social interactions and a negative mood, while adolescents with physical abuse were found to show an increase in aggressive behavior. These findings serve as a basis for this study, which investigates whether there is an interaction among the known risk factors and what effects they have on cognition and personality. The aim of this work is to investigate whether cognitive deficits exist in healthy subjects with the risk factors and whether certain personality traits are particularly pronounced. For this purpose, the risk allele of CACNA1C rs1006737 and the environmental factor “childhood trauma“ were each independently examined in groups for significant effects in neuropsychological testing. To measure the environmental factor, the Childhood Trauma Questionnaire was used. The NEO-Five-Factor Inventory was used to identify prominent personality traits within the groups. With the mentioned tests it was also examined whether there is a gene-environment interaction between the A allele of CACNA1C rs1006737 and the environmental factor “childhood trauma”. Also, it was investigated to what extent this interaction influences the cognition and personality of healthy subjects. The A-allele of the risk variant CACNA1C rs1006737 showed significant results in neuropsychological testing in the Subtest ‘Sum of Animals’ of the Regensburger Word Fluency Test (p=0.01) as well as loss interference in Verbal Learning And Memory Test (p=0.006). In contrast, the environmental factor in the Letter-Number Span showed a significant result (p=0.049). Further significant results of individual main effects did not occur. The interaction effect between the risk variant of CACNA1C and childhood trauma showed a significant result in the Subtest ‘Sum of Animals’ of the Regensburger Verbal Fluency Test as well as the Verbal Learning And Memory Test in learning performance and loss interference. Both risk factors did not confirm significant results in the evaluation of the NEO Five Factory Inventory. The interaction effect showed significant results for the characteristics neuroticism (p=0.016) and extraversion (p=0.039). In this study it could be confirmed that in healthy subjects effects on cognition occur due to the two risk factors gene and environment and their interaction. These were characterized by significantly worse results in the tests for semantic-categorical word fluency, as well as for declarative, episodic memory, and working memory. The two significant results in the personality test for the traits neuroticism and extraversion only occurred in the gene-environment interaction, which demonstrated an interaction effect of the A-allele of CACNA1C rs1006737 and childhood trauma. For the first time, this interaction effect in healthy subjects was demonstrated in this study using neuropsychological testing and in personality testing. The results of the risk gene variation partially confirmed already existing studies, which displayed deficits in word fluency. A comparison of the studies with the main factor “childhood trauma” is not conclusively possible, since a division into the subgroups of the Childhood Trauma Questionnaire did not take place due to a small sample group size. Further studies should take this into account and increase the group size. This would make it possible to determine which forms of childhood traumata are responsible for the interaction with the risk variant. In addition, it would be necessary to examine the significant personality traits of gene-environment interaction for their clinical relevance in everyday life. It should be borne in mind that only one SNP of a gene was tested and thus only one base pair exchange of a complete gene was examined. This limits the significance of the results. In this respect, a further assessment with regard to clinical relevance is not possible at this point in time. Further research should be conducted to determine whether the gene-environment interaction can be regarded as an additional risk factor for the onset of a psychiatric disease. If the interaction were to be confirmed again, the screening for the risk variant of healthy subjects with childhood trauma would certainly have to be considered in order to act preventively, before the onset of a psychiatric disorder.