Edaravone presents antidepressant-like activity in corticosterone model of depression in mice with possible role of Fkbp5, Comt, Adora1 and Slc6a15 genes.
Further, certain microRNAs (miRNAs), such as miR-124a and miR-18a, which could reduce GR protein expression, contribute to affective disorders, while miR-511 as a regulator of FKBP5 is involved in an increased risk of depression.
The significant interaction between ELA and the rs1360780 polymorphism in HATA suggests a role of FKBP5 in the pathophysiology of structural alterations in depression.
V.G.F. received honorarium for being a speaker for H. Lundbeck A/S.E.B.B. receives research funding from Böhringer Ingelheim to investigate FKBP5 as a potential drug target for depression.
However, FKBP5 methylation of these five CpG sites could not be validated as a valuable clinical biomarker for biological long-term effects of childhood maltreatment or lifetime depression.
Here, our objective was to assess mRNA levels of GC-related markers (GR, FKBP5, serum glucocorticoid kinase 1 [SGK1]) in patients with depression versus controls and in patient samples after electroconvulsive therapy (ECT).
The FK506-binding protein 51 (FKBP51) has emerged as a key regulator of endocrine stress responses in mammals and as a potential therapeutic target for stress-related disorders (depression, post-traumatic stress disorder), metabolic disorders (obesity and diabetes) and chronic pain.
Childhood adversity showed an interaction with the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism, serotonin transporter-linked promoter region (5-HTTLPR), and FK506 binding protein 51 (FKBP5) gene rs1360780 in brain morphologic changes in patients with depression and in a non-clinical population.
We assessed methylation levels at CpG sites in regions of the serotonin transporter (<i>SLC6A4</i>) previously associated with expression and depression outcomes, as well as the Intron 7 region of the FK506 binding protein 5 (<i>FKBP5</i>) containing known glucocorticoid response elements suggested to regulate this gene.
FKBP5 showed elevated expression levels in participants with vs. without a history of depression (p < 0.001); no significant difference in gene expression levels was observed in relation to childhood maltreatment (p > 0.05).
We also identified a female-specific association between FKBP5 mRNA expression and scores on the Beck Anxiety Inventory (r = 0.37, p = 0.013) and Beck Depression Inventory-II (r = 0.32, p = 0.033).
Our results suggest that an increased risk for depression may be transmitted from mother to child during fetal life and that the effect is dependent upon neonatal FKBP5 genotype.
In the model of depression employed here, decreases in MR expression and GR co-chaperone (FKBP51) levels in the hippocampus were also observed, and HFD intensified the prenatal stress-induced changes in MR expression.
Our results suggested FKBP5/GR and miR-124a in the BLA were associated with susceptibility to depressive disorder in the presence of stressful experiences in early life.
The association between DNA methylation of seven genes, including BDNF, SLC6A4, NR3C1, 5-HTR (1A, 2A, and 3A), FKBP5, MAO-A and OXTR, and depression were reviewed in this study.
Using Cox regression models and cumulative incidence plots, we analyzed the associations between genetic variants in 5-HTTLPR, BDNF, HTR1A, COMT, and FKBP5 and use of antidepressants as well as hospital contact for depression after diagnosis of cancer.
Our data reveals alterations of the communication patterns between the hippocampus and the rest of the brain in depression, effects potentially driven by overall familial factors (genes plus shared twin environment) and modified by the FKBP5 gene.
In the context of environmental stress, a functional variant in the glucocorticoid receptor co-chaperone FKBP5 gene has been repeatedly shown to increase risk for psychiatric illness, including depression.
Results indicate that genetic variation in FKBP5 influences the risk of anxiety and/or depressive disorders in preschool age by altering the sensitivity to the deleterious effects of mild to moderate adverse events.