@article{WiechmannRoehSaueretal.2019,
  author    = {Wiechmann, Tobias and R{\"o}h, Simone and Sauer, Susann and Czamara, Darina and Arloth, Janine and K{\"o}del, Maik and Beintner, Madita and Knop, Lisanne and Menke, Andreas and Binder, Elisabeth B. and Proven{\c{c}}al, Nadine},
  title     = {Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus},
  series = {Clinical Epigenetics},
  volume    = {11},
  journal   = {Clinical Epigenetics},
  doi       = {10.1186/s13148-019-0682-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233673},
  year      = {2019},
  abstract  = {Background Epigenetic mechanisms may play a major role in the biological embedding of early-life stress (ELS). One proposed mechanism is that glucocorticoid (GC) release following ELS exposure induces long-lasting alterations in DNA methylation (DNAm) of important regulatory genes of the stress response. Here, we investigate the dynamics of GC-dependent methylation changes in key regulatory regions of the FKBP5 locus in which ELS-associated DNAm changes have been reported. Results We repeatedly measured DNAm in human peripheral blood samples from 2 independent cohorts exposed to the GC agonist dexamethasone (DEX) using a targeted bisulfite sequencing approach, complemented by data from Illumina 450K arrays. We detected differentially methylated CpGs in enhancers co-localizing with GC receptor binding sites after acute DEX treatment (1 h, 3 h, 6 h), which returned to baseline levels within 23 h. These changes withstood correction for immune cell count differences. While we observed main effects of sex, age, body mass index, smoking, and depression symptoms on FKBP5 methylation levels, only the functional FKBP5 SNP (rs1360780) moderated the dynamic changes following DEX. This genotype effect was observed in both cohorts and included sites previously shown to be associated with ELS. Conclusion Our study highlights that DNAm levels within regulatory regions of the FKBP5 locus show dynamic changes following a GC challenge and suggest that factors influencing the dynamics of this regulation may contribute to the previously reported alterations in DNAm associated with current and past ELS exposure.},
  language  = {en}
}
@article{Menke2019,
  author    = {Menke, Andreas},
  title     = {Is the HPA axis as target for depression outdated, or is there a new hope?},
  series = {Frontiers in Psychiatry},
  volume    = {10},
  journal   = {Frontiers in Psychiatry},
  number    = {101},
  issn      = {1664-0640},
  doi       = {10.3389/fpsyt.2019.00101},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195780},
  year      = {2019},
  abstract  = {Major depressive disorder (MDD) is a very common stress-related mental disorder that carries a huge burden for affected patients and the society. It is associated with a high mortality that derives from suicidality and the development of serious medical conditions such as heart diseases, diabetes, and stroke. Although a range of effective antidepressants are available, more than 50\% of the patients do not respond to the first treatment they are prescribed and around 30\% fail to respond even after several treatment attempts. The heterogeneous condition of MDD, the lack of biomarkers matching patients with the right treatments and the situation that almost all available drugs are only targeting the serotonin, norepinephrine, or dopamine signaling, without regulating other potentially dysregulated systems may explain the insufficient treatment status. The hypothalamic-pituitary-adrenal (HPA) axis is one of these other systems, there is numerous and robust evidence that it is implicated in MDD and other stress-related conditions, but up to date there is no specific drug targeting HPA axis components that is approved and no test that is routinely used in the clinical setting identifying patients for such a specific treatment. Is there still hope after these many years for a breakthrough of agents targeting the HPA axis? This review will cover tests detecting altered HPA axis function and the specific treatment options such as glucocorticoid receptor (GR) antagonists, corticotropin-releasing hormone 1 (CRH1) receptor antagonists, tryptophan 2,3-dioxygenase (TDO) inhibitors and FK506 binding protein 5 (FKBP5) receptor antagonists.},
  language  = {en}
}