Pharmacopsychiatry 2025; 58(03): 146
DOI: 10.1055/s-0045-1807307
Abstracts | AGNP/DGBP
Poster

In major depression early response to antidepressant treatment in week one is associated with FKBP5-gene variants rs1360780 and rs4713916

T Mikoteit
1   Psychiatiric Services Solothurn, and Medical Faculty, University of Basel, Switzerland
,
S Galli
1   Psychiatiric Services Solothurn, and Medical Faculty, University of Basel, Switzerland
,
C Stäuble
2   Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Switzerland
,
M Zeising
3   Max Planck Institute of Psychiatry, Munich, Germany
,
A Steiger
3   Max Planck Institute of Psychiatry, Munich, Germany
,
E Binder
3   Max Planck Institute of Psychiatry, Munich, Germany
,
M Hatzinger
1   Psychiatiric Services Solothurn, and Medical Faculty, University of Basel, Switzerland
,
H E Meyer zu Schwabedissen
2   Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Switzerland
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Background: Major Depressive Disorder (MDD) is often associated with disinhibition of the hypothalamic-pituitary-adrenal (HPA) axis, which is regulated by negative feedback, when cortisol binds to glucocorticoid receptors (GR). GR sensitivity is reduced by the cochaperone FK506-binding protein 51 (FKBP51). Elevated FKBP51 activity reduces HPA feedback inhibition, and results in poor MDD trajectories. It is know that polymorphisms of the gene of FKBP51, FKBP5, are risk markers for non-response to antidepressant (AD) treatment after six weeks [1]. In this study, we investigated the impact of two FKBP5 variants (rs1360780 and rs4713916) on early treatment response in week one.

Methods: In eighty-one in-patients with MDD (M ± SD age = 44.29 ± 13.41 years, 52.5% female) depression severity was assessed with the Hamilton Depression Rating Scale (HDRS) at baseline and after one week of AD treatment. Genotyping of the FKBP5 variant rs1360780 with risk-allele T identified 9 T/T, 31 T/C and 41 C/C carriers, while for rs4713916 with risk-allele A we identified 8 A/A, 30 A/G and 43 G/G carriers. Both variants were in strong linkage equilibrium (D' = 0.831, r 2 = 0.637), so we examined their combination: six had two, 28 had one and 47 had no affected gene.

Results: Heterozygotes showed a greater HDRS-improvement at week one. This pattern was observed for both variants and with higher significance in linkage (t(78) = 2.166, p = 0.033, g = -0.512). According to categories &quot;early response&quot; or &quot;early non-response&quot; (ER: ≥ 30% HDRS reduction; n = 40; ENR: < 30% HDRS reduction; n = 40), ER manifested more likely in heterozygotes (X 2 (2) = 6.199, p = .045).

Conclusion: This study suggests FKBP5 genotype as a predictor to early AD treatment response. More specifically, the genotypes rs1360780 and rs4713916 and their combination were associated with ER in heterozygotes.



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Artikel online veröffentlicht:
30. April 2025

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