Epigenetic Influences in Aberrant Salience and Reality Testing in Schizoaffective Disorder: A Multi-Level Adaptive Network Modelling Approach

A fifth-order adaptive dynamical network model is introduced to examine the role of epigenetics in the development of schizoaffective disorder. The model’s focus is on the symptom of impaired reality testing and examines the impacts of aberrant salience and cortical disinhibition. Schizoaffective disorder is characterised through symptoms from schizophrenia and a mood disorder. The model demonstrates the impact that trauma has on the increased expression of DNA-methyltransferase 1, resulting in the hypermethylation of the GAD1 and GAD2 genes, and increased MeCP2 binding on promoter regions. The hypermethylation of GAD1 and GAD2 leads to decreased synthesis of GABA, with downstream effects on the dysregulation of glutamate and dopamine. Furthermore, the epigenetic effects of clozapine and valproate are explored in later simulations.