Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders
Childhood maltreatment is an important risk factor for adult depression and has been associated with changes in the hypothalamic pituitary adrenal (HPA) axis, including cortisol secretion and methylation of the <i>FKBP5</i> gene. Furthermore, associations between depression and HPA chang...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1485 |
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| author | Nora L. Großmann Antoine Weihs Luise Kühn Susann Sauer Simone Röh Tobias Wiechmann Monika Rex-Haffner Henry Völzke Uwe Völker Elisabeth B. Binder Alexander Teumer Georg Homuth Johanna Klinger-König Hans J. Grabe |
| author_facet | Nora L. Großmann Antoine Weihs Luise Kühn Susann Sauer Simone Röh Tobias Wiechmann Monika Rex-Haffner Henry Völzke Uwe Völker Elisabeth B. Binder Alexander Teumer Georg Homuth Johanna Klinger-König Hans J. Grabe |
| author_sort | Nora L. Großmann |
| collection | DOAJ |
| description | Childhood maltreatment is an important risk factor for adult depression and has been associated with changes in the hypothalamic pituitary adrenal (HPA) axis, including cortisol secretion and methylation of the <i>FKBP5</i> gene. Furthermore, associations between depression and HPA changes have been reported. This study investigated the associations of whole-blood <i>FKBP5</i> mRNA levels, serum cortisol levels, childhood maltreatment, and depressive symptoms with the whole-blood methylation status (assessed via target bisulfite sequencing) of 105 CpGs at the <i>FKBP5</i> locus using data from the general population-based Study of Health in Pomerania (SHIP) (<i>N</i> = 203). Both direct and interaction effects with the rs1360780 single-nucleotide polymorphism were investigated. Nominally significant associations of main effects on methylation of a single CpG site were observed at intron 3, intron 7, and the 3′-end of the gene. Additionally, methylation at two clusters at the 3′-end and intron 7 were nominally associated with childhood maltreatment × rs1360780 and depressive symptoms × rs1360780, respectively. The results add to the understanding of molecular mechanisms underlying the emergence of depression and could aid the development of personalised depression therapy and drug development. |
| first_indexed | 2024-03-08T03:55:49Z |
| format | Article |
| id | doaj.art-a05adad339b94856bd3b86b447ffc67a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:55:49Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a05adad339b94856bd3b86b447ffc67a2024-02-09T15:13:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253148510.3390/ijms25031485Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive DisordersNora L. Großmann0Antoine Weihs1Luise Kühn2Susann Sauer3Simone Röh4Tobias Wiechmann5Monika Rex-Haffner6Henry Völzke7Uwe Völker8Elisabeth B. Binder9Alexander Teumer10Georg Homuth11Johanna Klinger-König12Hans J. Grabe13Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment Genes and Environment, Max Planck Institute of Psychiatry, 80804 Munich, GermanyDepartment Genes and Environment, Max Planck Institute of Psychiatry, 80804 Munich, GermanyDepartment Genes and Environment, Max Planck Institute of Psychiatry, 80804 Munich, GermanyDepartment Genes and Environment, Max Planck Institute of Psychiatry, 80804 Munich, GermanyInstitute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, GermanyGerman Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment Genes and Environment, Max Planck Institute of Psychiatry, 80804 Munich, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyInterfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, GermanyChildhood maltreatment is an important risk factor for adult depression and has been associated with changes in the hypothalamic pituitary adrenal (HPA) axis, including cortisol secretion and methylation of the <i>FKBP5</i> gene. Furthermore, associations between depression and HPA changes have been reported. This study investigated the associations of whole-blood <i>FKBP5</i> mRNA levels, serum cortisol levels, childhood maltreatment, and depressive symptoms with the whole-blood methylation status (assessed via target bisulfite sequencing) of 105 CpGs at the <i>FKBP5</i> locus using data from the general population-based Study of Health in Pomerania (SHIP) (<i>N</i> = 203). Both direct and interaction effects with the rs1360780 single-nucleotide polymorphism were investigated. Nominally significant associations of main effects on methylation of a single CpG site were observed at intron 3, intron 7, and the 3′-end of the gene. Additionally, methylation at two clusters at the 3′-end and intron 7 were nominally associated with childhood maltreatment × rs1360780 and depressive symptoms × rs1360780, respectively. The results add to the understanding of molecular mechanisms underlying the emergence of depression and could aid the development of personalised depression therapy and drug development.https://www.mdpi.com/1422-0067/25/3/1485childhood maltreatmentdepressionHPAepigeneticsstresscortisol |
| spellingShingle | Nora L. Großmann Antoine Weihs Luise Kühn Susann Sauer Simone Röh Tobias Wiechmann Monika Rex-Haffner Henry Völzke Uwe Völker Elisabeth B. Binder Alexander Teumer Georg Homuth Johanna Klinger-König Hans J. Grabe Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders International Journal of Molecular Sciences childhood maltreatment depression HPA epigenetics stress cortisol |
| title | Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders |
| title_full | Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders |
| title_fullStr | Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders |
| title_full_unstemmed | Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders |
| title_short | Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders |
| title_sort | methylation patterns of the fkbp5 gene in association with childhood maltreatment and depressive disorders |
| topic | childhood maltreatment depression HPA epigenetics stress cortisol |
| url | https://www.mdpi.com/1422-0067/25/3/1485 |
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