Early-Life Adversity Interacts with FKBP5 Genotypes: Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project

William R. Lovallo, Mary Anne Enoch, Ashley Acheson, Andrew J. Cohoon, Kristen H. Sorocco, Colin A. Hodgkinson, Andrea S. Vincent, David Goldman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Exposure to stress during critical periods of development can have adverse effects on adult health behaviors, and genetic vulnerabilities may enhance these stress effects. We carried out an exploratory examination of psychological, physiological, and behavioral characteristics of 252 healthy young adults for the impact of early-life adversity (ELA) in relation to the G-to-A single nucleotide polymorphism (SNP), rs9296158, of the FKBP5 gene. FKBP5 is a molecular cochaperone that contributes to the functional status of the glucocorticoid receptor (GR) and to the quality of corticosteroid signaling. FKBP5 expression is upregulated by cortisol exposure during stressful episodes, with greater upregulation seen in A-allele carriers. As such, FKBP5 expression and GR function may be environmentally sensitive in A-allele carriers and therefore suitable for the study of gene-by-environment (G × E) interactions. Compared with FKBP5, GG homozygotes (N=118), A-allele carriers (N = 132) without psychiatric morbidity had progressively worse performance on the Stroop color-word task with increasing levels of ELA exposure (Genotype × ELA, F=5.14, P=0.007), indicating a G × E interaction on working memory in early adulthood. In addition, heart rate response to mental stress was diminished overall in AA/AG-allele carriers (F=5.15, P=0.024). Diminished working memory and attenuated autonomic responses to stress are both associated with risk for alcoholism and other substance use disorders. The present data suggest that FKBP5 in the GR pathway may be a point of vulnerability to ELA, as seen in this group of non-traumatized young adults. FKBP5 is accordingly a potential target for more extensive studies of the impact of ELA on health and health behaviors in adulthood.Neuropsychopharmacology advance online publication, 3 February 2016; doi:10.1038/npp.2015.347.

Original languageEnglish (US)
JournalNeuropsychopharmacology
DOIs
StateAccepted/In press - Dec 3 2015

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Family Health
Short-Term Memory
Genotype
Glucocorticoid Receptors
Alleles
Gene-Environment Interaction
Health Behavior
Young Adult
Homozygote
Alcoholism
Substance-Related Disorders
Single Nucleotide Polymorphism
Psychiatry
Hydrocortisone
Publications
Adrenal Cortex Hormones
Up-Regulation
Color
Heart Rate
Psychology

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Early-Life Adversity Interacts with FKBP5 Genotypes : Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project. / Lovallo, William R.; Enoch, Mary Anne; Acheson, Ashley; Cohoon, Andrew J.; Sorocco, Kristen H.; Hodgkinson, Colin A.; Vincent, Andrea S.; Goldman, David.

In: Neuropsychopharmacology, 03.12.2015.

Research output: Contribution to journalArticle

Lovallo, William R. ; Enoch, Mary Anne ; Acheson, Ashley ; Cohoon, Andrew J. ; Sorocco, Kristen H. ; Hodgkinson, Colin A. ; Vincent, Andrea S. ; Goldman, David. / Early-Life Adversity Interacts with FKBP5 Genotypes : Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project. In: Neuropsychopharmacology. 2015.
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