TY  - JOUR
A1  - Menke, Andreas
T1  - Is the HPA axis as target for depression outdated, or is there a new hope?
JF  - Frontiers in Psychiatry
N2  - 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.
KW  - precision medicine
KW  - personalized medicine
KW  - biomarker
KW  - depression
KW  - HPA axis
KW  - glucocorticoid receptor
KW  - CRH1
KW  - FKBP5
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195780
SN  - 1664-0640
VL  - 10
IS  - 101
ER  - 
TY  - JOUR
A1  - Vangeel, Elise Beau
A1  - Pishva, Ehsan
A1  - Hompes, Titia
A1  - van den Hove, Daniel
A1  - Lambrechts, Diether
A1  - Allegaert, Karel
A1  - Freson, Kathleen
A1  - Izzi, Benedetta
A1  - Claes, Stephan
T1  - Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for \(GABBR1\)
JF  - Clinical Epigenetics
N2  - Background: There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach.
Methods: We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome-wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n = 45) and candidate gene methylation using EpiTYPER (n = 80). Cortisol levels were measured at 2, 4, and 12 months of age to test infant stress system (re)activity.
Results: Data showed ten differentially methylated regions (DMR) when comparing newborns exposed to low versus high pregnancy anxiety scores. We validated a top DMR in the GABA-B receptor subunit 1 gene (GABBR1) revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R = 0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant cortisol levels in response to a routine vaccination at 4 months old.
Conclusions: In conclusion, our results show that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that our candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research.
KW  - DNA methylation
KW  - GABBR1
KW  - gender differences
KW  - HPA axis
KW  - pregnancy anxiety
KW  - prenatal stress
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173825
VL  - 9
ER  -