TY  - JOUR
AU  - Mihaljević, Marina
AU  - Franić, Dusanka
AU  - Soldatović, Ivan
AU  - Lukić, Iva
AU  - Andrić-Petrović, Sanja
AU  - Mirjanić, Tijana
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Zeljić, Katarina
AU  - Gašić, Vladimir
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
AU  - Marić, Nadja P.
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1451
AB  - 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.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Psychoneuroendocrinology
T1  - The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
VL  - 128
DO  - 10.1016/j.psyneuen.2021.105205
ER  - 

@article{
author = "Mihaljević, Marina and Franić, Dusanka and Soldatović, Ivan and Lukić, Iva and Andrić-Petrović, Sanja and Mirjanić, Tijana and Stanković, Biljana and Zukić, Branka and Zeljić, Katarina and Gašić, Vladimir and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav and Marić, Nadja P.",
year = "2021",
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.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Psychoneuroendocrinology",
title = "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls",
volume = "128",
doi = "10.1016/j.psyneuen.2021.105205"
}

Mihaljević, M., Franić, D., Soldatović, I., Lukić, I., Andrić-Petrović, S., Mirjanić, T., Stanković, B., Zukić, B., Zeljić, K., Gašić, V., Novaković, I., Pavlović, S., Adžić, M.,& Marić, N. P.. (2021). The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology
Pergamon-Elsevier Science Ltd, Oxford., 128.
https://doi.org/10.1016/j.psyneuen.2021.105205

Mihaljević M, Franić D, Soldatović I, Lukić I, Andrić-Petrović S, Mirjanić T, Stanković B, Zukić B, Zeljić K, Gašić V, Novaković I, Pavlović S, Adžić M, Marić NP. The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology. 2021;128.
doi:10.1016/j.psyneuen.2021.105205 .

Mihaljević, Marina, Franić, Dusanka, Soldatović, Ivan, Lukić, Iva, Andrić-Petrović, Sanja, Mirjanić, Tijana, Stanković, Biljana, Zukić, Branka, Zeljić, Katarina, Gašić, Vladimir, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, Marić, Nadja P., "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls" in Psychoneuroendocrinology, 128 (2021),
https://doi.org/10.1016/j.psyneuen.2021.105205 . .