Impacts of FKBP5 variants on large-scale brain network connectivity in healthy adults

FK506 binding protein 5 (FKBP5) rs1360780 polymorphism has been identified as a molecular genetic marker associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The impact of FKBP5 rs1360780 on the large-scale brain network connectivity in healthy adults is still unknown.

479 healthy volunteers (age: 20-80years) completed MRI scans, neuropsychological assessments and blood analysis.All subjects were divided into CC, CT and TT genotypes. Within and between network connectivities (10 sub-networks) were calculated using resting state functional MRI (rs-fMRI) data. The genetic effects and gene-gender/age interaction on large-scale network connectivity were explored.

Compared with CC and CT groups, TT group showed increased intra-connectivity in default mode network (DMN) and increased inter-connectivity mainly distributed among the network of DMN, salience network (SAN), dorsal attention network (DAN), ventral attention network (VAN), subcortical network (SUB), and visual network (VIS). Gene-by-gender and gene-by-age interaction were found in inter-connectivity of DAN to VIS and DMN to FPN, respectively. The altered connectivities correlated with anxiety status test score.

Plasma adrenocorticotropic hormone (ACTH) or cortisol were not measured,or else, we could estimate the hypothalamic-pituitary-adrenal (HPA) axis activity which may strengthen our results.

FKBP5 rs1360780 modulates the large-scale brain network connectivity in healthy adults. TT carriers showed the increased intra- and inter-connectivities mainly distributed among the network of DMN, SAN, DAN, VAN, SUB and VIS.