Childhood Trauma Involving Glucocorticoid Receptor Gene Exon1F On CpG Islands Undergoing DNA Methylation In Depression

BackgroundMajor depression today, accounts as the leading cause of disability in the whole world affecting people of all ages. Many years of research on animal models and human models have documented the impact of early childhood experiences on the neurobiological mechanism affecting the psychopathology of late adult life. Children are dependent on the caregivers and parents for their basic needs such as physical, social and emotional needs. Eventually, these children undergo substantial developmental changes in their neural pathways that determine emotions and behaviour. The hypothalamus-pituitary-adrenal (HPA) axis plays a major role in the regulation of the stress responses of the human body. However changes occurring to the HPA axis may give rise to stress and risks for psychiatric disorders. Taking into consideration the multiple promoters of the GR, the promoter1F in the CpG islands is more prone to methylation due to early life experiences. This study examines the status of DNA methylation occurring in the CpG islands of the GR promoter region1F in depressed patients with childhood trauma in China.MethodsIn order to avoid any bias and ensure the reliability and validity of this study, variables used for measuring childhood trauma and major depression were relatively adapted to the Chinese culture and the sampling design was also made to ensure a good representation of the Chinese population.60subjects (24males and36females) were recruited and divided into3groups of20; namely healthy individuals as control, depressed patients with childhood trauma and depressed patients without childhood trauma. The depressed patients were given scores according to5different CTQ subscales namely emotional neglect and abuse, physical neglect and abuse, and sexual abuse. The blood samples obtained from all the subjects were used to examine the degree of methylation of the human GR gene promoter region1F in lymphocytes DNA of the60participants. Moreover13CpG sites were identified to undergo Bisulphite pyrosequencing of the DNA. A two-tailed statistical significance was used to compare the three groups at P<0.05for all tests.ResultsIn this study the mean age groups of the subjects were a mean age±SD of29.55±5.60. Taking into consideration the child trauma exposure of the depressed patient; physical neglect (75%), emotional neglect (50%), sexual abuse (20%), physical abuse (20%) and emotional abuse (10%). It was also noticed that the depressed patients experiencing multiple exposures were55%and those exposed to a single exposure were45%. We first compared the MDD patients to the healthy controls, and noted that there were significant differences occurring particularly at CpG sites7and8with p<0.05. This relationship was furthermore evaluated after considering the effect of childhood trauma between the MDD patients (p<0.05). Depressed patients with childhood trauma were more likely to have higher levels of DNA methylation as compared to those without childhood trauma and to healthy controls (p<0.05), thus leading to a proper separation during clustering analyses. However no significant differences were found in the correlation after comparing the depressed patients without childhood trauma to healthy controls.ConclusionThe histories of CTE play an important role in the co-existence of DNA methylation and Major depression. The data obtained in this study suggest that there are two underlying mechanisms showing low expression of exon1F and also in the associated histories of depressive disorder with childhood trauma. This study shows that childhood trauma affects the DNA methylation status of the GR at the promoter region1F.(23pictures,10tables,74references)...