Hirnmorphologische Korrelate der Methylierung des Oxytocinrezeptorgens (OXTR) im Kontext elterlicher Bindung

Epigenetic factors have gained considerable traction alongside genetic and environmental risk factors in recent studies researching the etiology of psychoses, especially since epigenetics promises to be a link between the other. In this context the oxytocin receptor gene (OXTR) is deemed to be a key element in the development of attachments throughout live, both in interpreting social cues and maintaining interpersonal bonds. Both of which are known to be impeded by psychoses. In this thesis we aimed to uncover correlations between OXTR-methylation and morphological alterations of the brain. Furthermore, the impact of parental bonding of participants was to be assessed by analyzing said bonds and thereby creating a thorough model of the mechanisms that lead from disturbed parental bonding, via epigenetic alteration to morphological correlates. We recruited 62 healthy candidates from the FOR2107 „Marburg-Münster Affective Disorders Cohort Study“ (MACS) into a high-risk sample and gained epigenetic factors from whole blood via the Illumina Infinium MethylationEPIC BeadChip. In total, 18 CpG�Sites were analyzed, of which - after extensive research - 3 were chosen to be further explored. Furthermore, factor analysis was used to combine the original CpG-Sites into factors; in doing so, a gene-wide approach was also made possible. MR-images of all candidates were acquired for voxel-based morphometrics (VBM, using CAT12 in SPM12), gyrification-analysis (also using CAT12 in SPM12) and diffusion tensor imaging (DTI, using Tract-Based Spatial Statistics (TBSS) in FMRIB Software Library (FSL 5.0.7)). Parental bonding was assessed via the German version of the Parental Bonding Instrument (PBI) Correlating to increased methylation of single CpGs we found a significant reduction in the cortical grey matter of the superior temporal gyrus (STG) as well as reduced gyrification of the insula. In case of our DTI-analyses we found reduced integrity of cerebral white matter in many fasciculi, including the superior and inferior longitudinal fasciculus (S/ILF), as well as the inferior fronto-occipital fasciculus (IFOF). Regarding parental bonding, increased methylation-values of both factors and single CpGs correlated with axes of the PBI, among others regarding maternal care. In summary, our findings further substantiate the hypothesis of early childhood bonding affecting brain structure via epigenetic modification, and that especially the OXTR is a prime candidate for this connection. Variations in the cerebral structures we found to correlate with these epigenetic modifications had already been linked with many cases of psychoses.