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Introduction: Theory of mind (ToM) is important for social interactions and typical development and has been found to be impaired in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Hypoactivation in frontotemporal brain regions seems to be the underlying neural mechanism in AN while whole-brain analyses in BN are lacking.
Methods: We used the well-validated social recognition task fMRI paradigm to assess ToM in a total of 72 female adolescents (16 BN, 18 AN and 38 matched healthy controls [HC]).
Results: Compared to HCBN, patients with BN showed hyperactivity during ToM-activity in the right frontal pole, middle temporal gyrus and left temporal pole and differed fundamentally from hypoactivation in these regions observed in patients with AN before and after short-term weight rehabilitation. Interaction and overlap analyses confirmed that similar regions were affected in opposite directions in both diseases. Hyperactivations in BN in the right middle temporal gyrus and right frontal pole were associated with clinical BN-severity markers binging and purging frequency.
Discussion: The hyperactivation in BN suggest different underlying neural mechanisms for ToM compared to AN. Hyperactivity might correspond to a different but also ineffective cognitive style in patients with BN when approaching social interactions. These important transdiagnostic differences are relevant for future brain-targeted therapeutic approaches.
Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts. We aimed at exploring the epigenetic signature of females with CD and its relation to psychosocial and environmental risk factors. We performed HpaII sensitive genome-wide methylation sequencing of 49 CD girls and 50 matched typically developing controls and linear regression models to identify differentially methylated CpG loci (tags) and regions. Significant tags and regions were mapped to the respective genes and tested for enrichment in pathways and brain developmental processes. Finally, epigenetic signatures were tested as mediators for CD-associated risk factors. We identified a 12% increased methylation 5’ of the neurite modulator SLITRK5 (FDR = 0.0046) in cases within a glucocorticoid receptor binding site. Functionally, methylation positively correlated with gene expression in lymphoblastoid cell lines. At systems-level, genes (uncorr. P < 0.01) were associated with development of neurons, neurite outgrowth or neuronal developmental processes. At gene expression level, the associated gene-networks are activated perinatally and during early childhood in neocortical regions, thalamus and striatum, and expressed in amygdala and hippocampus. Specifically, the epigenetic signatures of the gene network activated in the thalamus during early childhood correlated with the effect of parental education on CD status possibly mediating its protective effect. The differential methylation patterns identified in females with CD are likely to affect genes that are expressed in brain regions previously indicated in CD. We provide suggestive evidence that protective effects are likely mediated by epigenetic mechanisms impairing specific brain developmental networks and therefore exerting a long-term effect on neural functions in CD. Our results are exploratory and thus, further replication is needed.