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

Abstract

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.

Associations between glucocorticoids and sociality across a continuum of vertebrate social behavior

“…Elevated HPA-axis activity may have varied effects on these different aspects of social coordination among group members. First, GCs can affect event memory as different stressors are known to affect memory performance, both by impairing some aspects of memory while enhancing others (Packard et al, 2016;Takahashi et al, 2004;Zoladz et al, 2017). For instance, Zebra Finches with experimentally elevated GCs had lower event memory and were unable to sustain cooperation in a prisoner's dilemma task (Larose & Dubois, 2011).…”

KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients

“…While cognitive function can be compromised by neurodegeneration, exogenous stress is also an established risk factor for impairment of learning and memory and so provides an important model for investigating cognitive resilience 20 . The FKBP5 gene encodes FK506-binding protein 51 (FKBP51), and the T allele carriers tend to exhibit increased mRNA expression levels of FKBP5 21 .…”

Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders

“…The polymorphism in fkbp5 has also been shown to predict individual differences in stress-related memory deficits [e.g., 162 , 163 ] and functional activity/connectivity of the amygdala related to emotional (anxiety/depression) responses to threat [e.g., 164 – 168 ]. Its interaction with early life stress is also predictive of reduced connectivity between the amygdala and parahippocampal gyrus, caudate, and frontal gyri [ 169 ; see also 170 ].…”

“…In healthy undergraduate students, exposure to a socially evaluative cold pressor test directly prior to verbal learning reduced immediate verbal recall in fkbp5 risk allele carriers (rs1360780, rs3800373 and rs929615). In contrast, the stress task enhanced 24-h later recall and recognition memory in non-carriers of the risk alleles [ 163 ]. In young healthy adults, fkbp5 A-allele carriers had less pronounced autonomic responses to stress and poor working memory performance on the Stroop color-word task (the results of which positively correlated to the degree of self-reported early life adversity), which was associated with poor health behaviors when compared to fkbp5 GG homozygotes [ 162 ].…”