title: Early-Life Adversity Interacts with FKBP5 Genotypes: Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project.
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.
authors.affiliation: VA Medical Center, Oklahoma City, OK, USA.|Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Lovallo
authors.affiliation: Laboratory of Neurogenetics, NIH, NIAAA, Bethesda, MD, USA.
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.affiliation: Department of Psychiatry, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA.|Research Imaging Institute, UTHSCSA, San Antonio, TX, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Acheson
authors.affiliation: VA Medical Center, Oklahoma City, OK, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cohoon
authors.affiliation: VA Medical Center, Oklahoma City, OK, USA.|Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Sorocco
authors.affiliation: Laboratory of Neurogenetics, NIH, NIAAA, Bethesda, MD, USA.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.affiliation: Cognitive Science Research Center, University of Oklahoma, Norman, OK, USA.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Vincent
authors.affiliation: Laboratory of Neurogenetics, NIH, NIAAA, Bethesda, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Goldman
mesh_terms: D000293:Adolescent; D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology; D005192:Family Health; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006339:Heart Rate / Q000235:genetics* / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007175:Impulsive Behavior / Q000502:physiology; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009825:Oklahoma; D010555:Personality Inventory; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D013694:Temperament / Q000502:physiology; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D006854:Hydrocortisone; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5