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 language | English (US) |
|---|---|
| Journal | Neuropsychopharmacology |
| DOIs | |
| State | Accepted/In press - Dec 3 2015 |
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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 journal › Article
}
TY - JOUR
T1 - Early-Life Adversity Interacts with FKBP5 Genotypes
T2 - Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project
AU - Lovallo, William R.
AU - Enoch, Mary Anne
AU - Acheson, Ashley
AU - Cohoon, Andrew J.
AU - Sorocco, Kristen H.
AU - Hodgkinson, Colin A.
AU - Vincent, Andrea S.
AU - Goldman, David
PY - 2015/12/3
Y1 - 2015/12/3
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84959287999&partnerID=8YFLogxK
U2 - 10.1038/npp.2015.347
DO - 10.1038/npp.2015.347
M3 - Article
C2 - 26632991
AN - SCOPUS:84959287999
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
ER -