Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/4257
Title: The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
Authors: Mihaljevic, Marina
Franic, Dusanka
Soldatovic, Ivan
Lukic, Iva
Petrovic, Sanja Andric
Mirjanic, Tijana
Stankovic, Biljana
Zukic, Branka
Zeljić, Katarina 
Gasic, Vladimir
Novakovic, Ivana
Pavlovic, Sonja
Adzic, Miroslav
Maric, Nadja P.
Keywords: FKBP5 methylation;Psychosis;HPA axis;Childhood trauma;Unaffected siblings
Issue Date: 2021
Rank: M21
Publisher: Elsevier Ltd
Citation: Marina Mihaljevic, Dusanka Franic, Ivan Soldatovic, Iva Lukic, Sanja Andric Petrovic, Tijana Mirjanic, Biljana Stankovic, Branka Zukic, Katarina Zeljic, Vladimir Gasic, Ivana Novakovic, Sonja Pavlovic, Miroslav Adzic, Nadja P. Maric, “The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls”, Psychoneuroendocrinology, Volume 128, 2021.
Journal: Psychoneuroendocrinology
Abstract: 
Hypothalamic–pituitary–adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis.

A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT.

Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings.

We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.
URI: https://biore.bio.bg.ac.rs/handle/123456789/4257
ISSN: 0306-4530
DOI: 10.1016/j.psyneuen.2021.105205
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