Der Einfluss des Einzelnukleotidpolymorphismus rs1006737 des Gens CACNA1C auf neuronale Korrelate des Arbeitsgedächtnisses- Eine Studie mit funktioneller Magnetresonanztomographie

The present study was focused on the question whether there are neuronal correlates of working memory which show association with the influence of the single nucleotide polymorphism rs1006737 of the gene CACNA1C. In the past rs1006737 in CACNA1C was repeatedly associated with high susceptibility for bipolar disorder and schizophrenia. According to current assumptions, variation in neuronal structures and processes underlies these disorders and has an impact on working memory especially in dorsolateral prefrontal cortex (DLPFC). In my thesis I investigated 94 healthy human subjects using functional magnetic resonance tomography. It was shown that homozygous A-allele carriers present significant lower activation in the right DLPFC during working memory execution compared with heterozygous and non-risk-allele carriers. These results are in contrast to previous studies. Data published so far provide evidence that the influence of rs1006737 leads to stronger activation in the right DLPFC. In 2010, Bigos and colleagues calculated an activation analysis to prove this effect. They found an increase of activation within the range of the right DLPFC which is associated with carriers of the single nucleotide polymorphism rs1006737 in CACNA1C (Bigos et al., 2010, Genetic variation in CACNA1C affects brain circuitries related to mental illness: Arch Gen Psychiatry, v. 67, p. 939-45). Summing up, the results obtained in the present study challenge previous data. In consequence, a re-evaluation and re-interpretation of the influence of rs1006737 in the CACNA1C gene on neuronal correlates in the working memory process is demanded.