The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
Само за регистроване кориснике
2021
Аутори
Mihaljević, MarinaFranić, Dušanka
Soldatović, Ivan A.
Lukić, Iva
Andrić-Petrović, Sanja
Mirjanić, Tijana
Stanković, Biljana
Žukić, Branka
Željić, Katarina
Gašić, Vladimir
Novaković, Ivana
Pavlović, Sonja
Adžić, Miroslav
Marić, Nađa P.
Чланак у часопису (Објављена верзија)
,
© 2021 Elsevier Ltd.
Метаподаци
Приказ свих података о документуАпстракт
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 FKB...P5 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. © 2021 Elsevier Ltd
Кључне речи:
Childhood trauma / FKBP5 methylation / HPA axis / Psychosis / Unaffected siblingsИзвор:
Psychoneuroendocrinology, 2021, 128, 105205-Финансирање / пројекти:
- European Network of National Schizophrenia Networks Studying Gene-Environment Interactions –EUGEI [HEALTH-F2-2010-241909]
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200017 (Универзитет у Београду, Институт за нуклеарне науке Винча, Београд-Винча) (RS-MESTD-inst-2020-200017)
- Ретке болести: молекуларна патофизиологија, дијагностички и терапијски модалитети и социјални, етички и правни аспекти (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
DOI: 10.1016/j.psyneuen.2021.105205
ISSN: 0306-4530
PubMed: 33933892
WoS: 000651466100021
Scopus: 2-s2.0-85105254693
Институција/група
VinčaTY - JOUR AU - Mihaljević, Marina AU - Franić, Dušanka AU - Soldatović, Ivan A. AU - Lukić, Iva AU - Andrić-Petrović, Sanja AU - Mirjanić, Tijana AU - Stanković, Biljana AU - Žukić, Branka AU - Željić, Katarina AU - Gašić, Vladimir AU - Novaković, Ivana AU - Pavlović, Sonja AU - Adžić, Miroslav AU - Marić, Nađa P. PY - 2021 UR - https://vinar.vin.bg.ac.rs/handle/123456789/9748 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. © 2021 Elsevier Ltd 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 SP - 105205 DO - 10.1016/j.psyneuen.2021.105205 ER -
@article{ author = "Mihaljević, Marina and Franić, Dušanka and Soldatović, Ivan A. and Lukić, Iva and Andrić-Petrović, Sanja and Mirjanić, Tijana and Stanković, Biljana and Žukić, Branka and Željić, Katarina and Gašić, Vladimir and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav and Marić, Nađa 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. © 2021 Elsevier Ltd", 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", pages = "105205", doi = "10.1016/j.psyneuen.2021.105205" }
Mihaljević, M., Franić, D., Soldatović, I. A., Lukić, I., Andrić-Petrović, S., Mirjanić, T., Stanković, B., Žukić, B., Željić, 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, 128, 105205. https://doi.org/10.1016/j.psyneuen.2021.105205
Mihaljević M, Franić D, Soldatović IA, Lukić I, Andrić-Petrović S, Mirjanić T, Stanković B, Žukić B, Željić 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;128:105205. doi:10.1016/j.psyneuen.2021.105205 .
Mihaljević, Marina, Franić, Dušanka, Soldatović, Ivan A., Lukić, Iva, Andrić-Petrović, Sanja, Mirjanić, Tijana, Stanković, Biljana, Žukić, Branka, Željić, Katarina, Gašić, Vladimir, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, Marić, Nađa 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):105205, https://doi.org/10.1016/j.psyneuen.2021.105205 . .