The influence of rs1360780 polymorphism of FK506-binding protein 5 gene on the brain regional homogeneity of resting state fMRI in patients with major depressive disorder

Objective To explore the influence of rs1360780 T risk allele of FK506-binding protein 5 (FKBP5) gene on the brain function under resting-state and its association with clinical symptoms as well as immune function in patients with major depressive disorder (MDD). Methods Totally 147 MDD patients and 61 gender-, age-, and education-matched healthy controls were scanned with 3.0T MRI Scanner and genotyped. The peripheral serum immunoglobulin and complement were measured. The main effect of the disease, the genotype and their interaction effects were analyzed using regional homogeneity (ReHo) by two-way ANOVA. Abnormal brain activity was identified in T risk allele carriers of rs1360780 and non-risk CC individuals in MDD using post hoc analyses. Correlation analyses were performed between ReHo values of significant brain regions and the total score, five-factor scores of Hamilton rating scale for depression (HAMD-17), serum levels of immunoglobulin and plasma complement component in MDD patients. Results (1)The results of 2×2 ANOVA showed the interaction effects located in the left opercular part of inferior frontal gyrus (MNI: x, y, z=-42, 6, 9; F=10.83), right opercular part of inferior frontal gyrus (MNI: x, y, z=30, 6, 33; F=15.05), left medial superior frontal gyrus (MNI: x, y, z=-9, 54, 0; F=9.17) and left pallidum (MNI: x, y, z=-12, 6, -6; F=11.37) (Alphasim corrected, P<0.05). (2)In post-hoc analyses for the main effect of genotype, T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI: x, y, z=60, 12, 6; t=2.88) compared with CC carriers; for the effect of disease-by-genotype interaction, T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI: x, y, z=30, 6, 33; t=2.96) and decreased ReHo values in the left orbital part of inferior frontal gyrus (MNI: x, y, z=-21, 9, -18; t=-3.21) (Alphasim corrected, P<0.05) in contrast to CC carriers.(3)Pearson's correlation showed that the average ReHo values of the right opercular part of inferior frontal gyrus negatively correlated with the content of immunoglobulin G (r=-0.528, P=0.0016, Bonferroni corrected) and positively correlated with anxiety/somatization factor score (r=0.421, P<0.001, Bonferroni corrected) in T+ carriers with MDD. Conclusion The results of this study suggest that rs1360780 T-risk allele of FKBP5 gene is involved in the changes of local neural activity in the right opercular part of inferior frontal gyrus of depressed patients and could potentially indicate a neuropathological mechanism of anxiety somatic symptoms and immune dysfunction in depression. Key words: Depression; FK506-binding protein 5; Gene-imaging; Regional homogeneity; Immune function