Adverse Childhood Experiences and Methylation of the FKBP5 Gene in Patients with Psychotic Disorders

Altered methylation of the gene has been observed in various mental disorders and attributed to the effects of adverse childhood experiences (ACEs). However, the level of methylation has not been investigated in patients with psychotic disorders. Therefore, in this study we aimed to determine the methylation in patients with psychosis and controls, taking into account the effects of ACEs. Participants were 85 patients with psychotic disorders, including first-episode psychosis (FEP) patients and acutely relapsed schizophrenia (SCZ-AR) patients, as well as 56 controls. The level of four CpG sites at the gene was determined in the peripheral blood leukocytes using pyrosequencing. After controlling for potential confounding factors, the level of methylation at one out of four tested CpG sites was significantly lower in FEP patients compared to other groups of participants. Significant main effects of parental antipathy and sexual abuse on the level of methylation were observed at the differentially methylated CpG site. Participants reporting this category of ACEs had significantly lower levels of methylation at this CpG site. Lower levels of methylation were associated with better cognitive performance and higher functional capacity in patients with psychosis. In controls, lower methylation of was related to worse performance of immediate memory and language skills. Our findings suggest that hypomethylation of the appears at early stages of psychosis and might be associated with a history of ACEs as well as less severe clinical manifestation.