FKBP5 polymorphism is associated with major depression but not with bipolar disorder

Szczepankiewicz, Aleksandra; Leszczyńska-Rodziewicz, Anna; Pawlak, Joanna; Narożna, Beata; Rajewska‐Rager, Aleksandra; Wiłkość, Monika; Zaremba, Dorota; Maciukiewicz, Małgorzata; Twarowska-Hauser, Joanna

doi:10.1016/j.jad.2014.04.002

Cited by 86 publications

(67 citation statements)

References 31 publications

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“…However, it is important to note that psychiatric disorders might be diagnosed in as high as 90% of suicide victims [34]. Psychiatric disorders, such as major depression, bipolar disorder, or PTSD, which impact HPA axis activity, were also previously reported to be associated with FKBP5 alternations [19,21,35,36]. Therefore, we cannot exclude the possibility that these psychiatric conditions were present but not diagnosed in the present sample and could have influenced the results of the study.…”

Section: Discussionmentioning

confidence: 99%

Association between FKBP5 Functional Polymorphisms and Completed Suicide

Fudalej¹,

Kopera²,

Wołyńczyk-Gmaj³

et al. 2015

Neuropsychobiology

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Objectives: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis leads to impaired stress response. FK506-binding protein 51 (FKBP5), which influences HPA axis activity via glucocorticoid receptors, is supposed to play an important role in the regulation of negative feedback and glucocorticoid resistance. Since ineffective stress response mechanisms are considered as a biological background of suicide behavior, we aimed to analyze a possible association between FKBP5 functional polymorphisms and completed suicide. Methods: The selected FKBP5 polymorphisms rs1360780 and rs3800373 were genotyped in a sample of 563 suicide victims and 475 controls. Results: A significant association between the high-induction rs3800373 C allele and completed suicide was detected (OR = 1.36, p = 0.007). In this polymorphism, genotype distribution supported a codominant model of inheritance. The analyzed SNPs were in strong linkage disequilibrium (D' = 0.916 and r² = 0.826) with the rs1360780 (T)-rs3800373 (C) haplotype apparently responsible for the observed association (OR = 1.34, p = 0.010). Conclusion: The results of the present study indicate that genetic alterations in FKBP5 may influence vulnerability to suicide.

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Section: Discussionmentioning

confidence: 99%

Association between FKBP5 Functional Polymorphisms and Completed Suicide

Fudalej¹,

Kopera²,

Wołyńczyk-Gmaj³

et al. 2015

Neuropsychobiology

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“…Genetically based disturbances in FK506 function have been linked to dysfunctions in HPA axis, both in the general population [36] and in patients with stress-related disorders [37]. Additionally, FK506 function alterations have been linked to psychiatric disorders such as major depression which, like BPD, are characterized by disturbances in HPA axis [38,39]. Although the polymorphisms associated with BPD are intronic variants of unknown functionality, our results suggest a possible involvement of FKBP5 in the aetiology of BPD.…”

Section: Discussionmentioning

confidence: 99%

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

Martín-Blanco

Ferrer

Soler

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

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“…The rs1360780 T allele was identified as the risk allele by three studies, the rs9470080 T allele by two studies, and the rs3800373 C allele by one study (Zannas and Binder 2014). Some studies did not take into account FKBP5 environment interactions and three studies found that the rs1360780 T allele was associated with increased risk of depression (Lekman et al 2008;Lavebratt et al 2010;Szczepankiewicz et al 2014), two studies found an effect of rs4713916 (Zobel et al 2010;Szczepankiewicz et al 2014), and non-replicated findings were reported for rs9470080, rs9296158 (Szczepankiewicz et al 2014) and rs3800373 (Zobel et al 2010).…”

Section: Genetic Polymorphismsmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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FKBP5 polymorphism is associated with major depression but not with bipolar disorder

Cited by 86 publications

References 31 publications

Association between <b><i>FKBP5</i></b> Functional Polymorphisms and Completed Suicide

Association between <b><i>FKBP5</i></b> Functional Polymorphisms and Completed Suicide

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

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