Genetic Variants in Serotonin and Corticosteroid Systems Modulate Neuroendocrine and Cardiovascular Responses to Intense Stress
Abstract
Common variants in serotonin and corticosteroid receptor genes influence human stress in laboratory settings. Little is known of their combined effects. This study evaluated distinct and combined effects of polymorphisms in the serotonin transporter (5HTTLPR L/S), glucocorticoid receptor (Bcl1 C/G), and mineralocorticoid (-2C/G) receptor genes on adrenocortical and cardiovascular reactions to intense, realistic stress. The study took place within a 12-day military survival course. Participants were studied before, during, and 24 hours after the course. One hundred forty-four healthy, active-duty military men were studied. Dependent variables were cortisol, heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP). 5HTTLPR SS carriers revealed higher overall cortisol concentrations than L-carriers (p = .022). 5HTTLPR L-carriers demonstrated higher stress-induced HR than non-carriers (SS) yet rebounded to a lower recovery value (p = .026), while Bcl1 G carriers showed higher mean stress-induced HR than non-carriers (CC) (p = .047). For DBP, 5HTTLPR S carriers showed higher overall values than non-carriers (LL) (p = .043), Bcl1 GG were higher than C carriers (p = .039), and -2C/G G carriers exceeded non-carriers (CC) (p = .028). A "high" haplotype revealed substantially higher overall cortisol concentrations than a "low" haplotype (p less than .001), as was the case for DBP (p = .037). This study revealed synergistic effects of common polymorphisms on human responses to intense stress. These findings may have implications for drug discovery, gene therapy, and stress inoculation strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 10, 2014
- Accession Number
- ADA619323
Entities
People
- Gerald E. Larson
- Marcus K. Taylor
- Melissa D. Hiller-lauby
Organizations
- Naval Health Research Center