title: Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces.
abstract: The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high < SS/low = L/high < L/low). Thus, 5HTTLPR and prior trauma exposure demonstrated counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings.
authors.affiliation: Biobehavioral Sciences Lab, Warfighter Performance Department, Naval Health Research Center, 140 Sylvester Road, San Diego, CA, USA; School of Exercise and Nutritional Sciences, San Diego State University, ENS Building Room 351, 5500 Campanile Drive, San Diego, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, Arizona State University, 550 E. Orange Street, Tempe, AZ, USA. Electronic address: marcus.k.taylorz.civ@mail.mil.
authors.forename: Marcus K
authors.initials: MK
authors.lastname: Taylor
authors.affiliation: Biobehavioral Sciences Lab, Warfighter Performance Department, Naval Health Research Center, 140 Sylvester Road, San Diego, CA, USA; School of Exercise and Nutritional Sciences, San Diego State University, ENS Building Room 351, 5500 Campanile Drive, San Diego, CA, USA. Electronic address: jennifer.carpenter2@gmail.com.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Carpenter
authors.affiliation: Biobehavioral Sciences Lab, Warfighter Performance Department, Naval Health Research Center, 140 Sylvester Road, San Diego, CA, USA; School of Exercise and Nutritional Sciences, San Diego State University, ENS Building Room 351, 5500 Campanile Drive, San Diego, CA, USA. Electronic address: stonemi13@aol.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Stone
authors.affiliation: Biobehavioral Sciences Lab, Warfighter Performance Department, Naval Health Research Center, 140 Sylvester Road, San Diego, CA, USA; School of Exercise and Nutritional Sciences, San Diego State University, ENS Building Room 351, 5500 Campanile Drive, San Diego, CA, USA. Electronic address: lisa.m.hernandez75.ctr@mail.mil.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hernandez
authors.affiliation: Biobehavioral Sciences Lab, Warfighter Performance Department, Naval Health Research Center, 140 Sylvester Road, San Diego, CA, USA; School of Exercise and Nutritional Sciences, San Diego State University, ENS Building Room 351, 5500 Campanile Drive, San Diego, CA, USA. Electronic address: mitchell.rauh@med.navy.mil.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Rauh
authors.affiliation: Institute for Interdisciplinary Salivary Bioscience Research, Arizona State University, 550 E. Orange Street, Tempe, AZ, USA; Department of Psychology, 1227 University of Oregon, Eugene, OR, USA. Electronic address: hlaurent@uoregon.edu.
authors.forename: Heidemarie K
authors.initials: HK
authors.lastname: Laurent
authors.affiliation: Institute for Interdisciplinary Salivary Bioscience Research, Arizona State University, 550 E. Orange Street, Tempe, AZ, USA; Johns Hopkins School of Nursing and Bloomberg School of Public Health, 3400 North Charles Street, Baltimore, MD, USA. Electronic address: douglas.granger@asu.edu.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Granger
mesh_terms: D000293:Adolescent; D000328:Adult; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism*; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008571:Men; D008875:Middle Aged; D008889:Military Personnel; D020932:Nerve Growth Factor / Q000378:metabolism*; D055500:Resilience, Psychological; D012463:Saliva / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D020932:Nerve Growth Factor; D006854:Hydrocortisone
keywords: Cortisol; Dehydroepiandrosterone sulfate; Genetics; Nerve growth factor; Serotonin transporter; Stress; Testosterone; Trauma