Potential role of FKBP5 single‐nucleotide polymorphisms in functional seizures

Abstract

Objective We investigated the associations between FKBP5 single‐nucleotide polymorphisms (SNPs) and functional seizures (FS). Methods Seventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3′ region and rs9470080 in the 5′ region of the FKBP5. Childhood trauma questionnaire and hospital anxiety and depression scale were used. Results Patients with FS and those with MDD had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. Similar results were observed for allelic frequencies. There were no significant differences between FS and MDD groups in terms of genotype and allelic frequencies for both SNPs. The results of multinomial logistic regression analysis showed that FKBP5 polymorphisms were not associated with the diagnosis. Significance Patients with FS and those with MDD had significantly different genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. However, it seems that FKBP5 polymorphisms were not associated with FS in the absence of depression. Further genetic investigations of patients with FS may increase our understanding of the neurobiological underpinnings of this condition, but such studies should be large enough and very well designed; they should include a comparison group with depression in addition to a healthy control group.

FKBP5 blockade may provide a new horizon for the treatment of stress‐associated disorders: An in‐silico study

“…18,19 In one recent study, the authors showed that the hypothesis of the association between FKBP5 single nucleotide polymorphisms (SNPs) and FS is a plausible hypothesis. 20 In that study, patients with FS had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with healthy controls. However, they could not show whether FKBP5 polymorphisms were associated with FS in the absence of depression.…”

“…In that study, patients with FS had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with healthy controls. However, they could not show whether FKBP5 polymorphisms were associated with FS in the absence of depression 20 . Another study showed that patients with FS have basal hypercortisolism that is independent of the acute occurrence of seizures 21 .…”

“…However, they could not show whether FKBP5 polymorphisms were associated with FS in the absence of depression. 20 Another study showed that patients with FS have basal hypercortisolism that is independent of the acute occurrence of seizures. 21 These two findings are in line with the studies that have provided evidence on the interactions between FKBP5 genotypes and early-life stress to pose a risk for stress-associated disorders (eg, major depression and PTSD).…”

“…Functional seizures are associated with life stresses (eg, sexual abuse or medical comorbidities), at least in many of these patients 18,19 . In one recent study, the authors showed that the hypothesis of the association between FKBP5 single nucleotide polymorphisms (SNPs) and FS is a plausible hypothesis 20 . In that study, patients with FS had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with healthy controls.…”

Cannabidiol for functional seizures (psychogenic nonepileptic seizures/attacks) and other stress‐associated disorders

“…To the Editor, Recently, we published a paper that suggested that FKBP5 single-nucleotide polymorphisms may play a role in functional seizures (psychogenic nonepileptic seizures/attacks). 1 We also published another paper entitled "FKBP5 blockade may provide a new horizon for the treatment of stress-associated disorders: An in-silico study" providing a list of the currently available and approved drugs (e.g., fluticasone propionate, prednisolone, dexamethasone, mirtazapine, sertraline, fluoxetine, and citalopram) that could potentially be used for this purpose. 2 More recently, I read an article entitled: "Cannabidiol alleviates neuroinflammation and attenuates neuropathic pain via targeting FKBP5."…”