FKBP5 polymorphisms influence pre‐learning stress‐induced alterations of learning and memory

• Published in: The European journal of neuroscience Vol. 45; no. 5; pp. 648 - 659
• Main Authors: Zoladz, Phillip R., Dailey, Alison M., Nagle, Hannah E., Fiely, Miranda K., Mosley, Brianne E., Brown, Callie M., Duffy, Tessa J., Scharf, Amanda R., Earley, McKenna B., Rorabaugh, Boyd R., Rossell, Susan
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.03.2017
• Subjects: Alleles; Bipolar disorder; Cognitive ability; Cold pressing; Corticosteroids; Cortisol; Depression; Emotions; Female; FKBP5; Genotyping; Glucocorticoids; Heat shock proteins; Heterozygote; Hsp90 protein; Humans; Hypothalamus; Learning; Male; Memory; Mental depression; Mental disorders; Mental Recall; Pituitary; Polymorphism, Single Nucleotide; Post traumatic stress disorder; Receptor mechanisms; Saliva; Single-nucleotide polymorphism; stress; Stress, Psychological - genetics; Structure-function relationships; Tacrolimus; Tacrolimus Binding Proteins - genetics; Tacrolimus-binding protein; Young Adult; cortisol; stress; learning; memory; FKBP5
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.13514

FK506 binding protein 51 (FKBP5) is a co‐chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus–pituitary–adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post‐traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long‐term recall and recognition memory in non‐carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow‐up analyses revealed that memory performance was correlated with salivary cortisol levels in non‐carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress‐induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress‐related psychological disorders and their related phenotypes. Exposure to brief stress immediately before learning enhanced long‐term memory in non‐carriers, but not carriers, of minor alleles for three different FKBP5 polymorphisms. These findings suggest that carriers of such “risk” alleles for FKBP5 may possess a sensitized stress response system, which might aid in our understanding of how SNPs in the FKBP5 gene confer increased risk for stress‐related psychological disorders.