Task Progress:
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In year 1, the Hensch lab established the physiological and behavioral consequences of early life stress (ELS) in mice. In a paradigm of fragmented maternal care (neglect), striking sex-specific outcomes were observed. Male mice raised under fragmented maternal care displayed externalizing behaviors as adults, including social dominance, increased territoriality, compulsive behaviors, and social memory deficits. Instead, females exhibited internalizing symptoms, like heightened anxiety and perseveration on a rule-switching task. Inhibitory sub-circuits within the prefrontal cortex (PFC) were also differentially affected by sex following ELS: males showed enhanced inhibition of callosal projections, while females had reduced inhibition of sub-cortical projections. These findings indicate the early life history of subjects predisposes them to mental states which need to be considered prior to engaging in long-term spaceflight. They further suggest local circuit changes may be targeted differentially to correct later adult psychopathology in males and females raised under early adversity.
The following biomarkers, which have all been associated with stress, emotional, or immune responses in prior research, will be determined in venous blood samples (8 ml serum) collected at baseline and on a regular basis throughout the 3 ICC/E environments: Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1) (Lin, Suhr et al. 2014) , Neuropeptide Y (NPY), Ghrelin and oxytocin, tumor necrosis factor (TNF) (Beste, Baune et al. 2010; Hodes, Pfau et al. 2014; van Zuiden, Kavelaars et al. 2015), interleukin-1 (IL-1), interleukin-6 (IL-6) (Valkanova, Ebmeier et al. 2013), interleukin-10 (IL-10), and vitamin D. Blood samples will be taken by venipuncture in the morning after overnight fasting between 7 and 8 am to avoid circadian rhythm confounds. The Vacutainer® Safety-Lok TM Blood Collection Set and SST TM Tubes with Silica Clot Activator (Beckton, Dickinson & Company) from clinical suppliers certified as medical products (Sarstedt system) will be used to perform the blood draw. Immediately after collection serum samples will be centrifuged for 10 min at 1000 g, and then aliquoted in 8 cryovials of 250 µl each and then stored at -80°C. Serum parameters will be analyzed by ELISA (enzyme-linked immunoarbsorbat assay) kits (R&D Systems GmbH, Wiesbaden, Germany / IBL International GmbH, Hamburg, Germany). Cortisol will be determined from morning collections of saliva specimens, which will be collected by chewing on a salivette for approximately 3 minutes until it is soaked (Salivette; Sarsted, Rommelsdorf, Germany). Samples are immediately centrifuged at 1500 g for 15 min, and will then be stored at –80°C until shipping to Germany. Samples are analyzed for free cortisol by ELISA in accordance with the manufacturer’s instructions (IBL International GmbH, Hamburg, Germany). On the same days as blood draws, we will gather 24 h ECG data (e.g., with the eMotion FAROS sensor (Mega Electronics Ltd., Kuopio, Finland) to derive heart rate and heart rate variability measures as a peripheral index of emotion regulatory processes that are affected by prefrontal mechanisms.
Analysis will encompass the biological basis of social support to assess individual sociability and the neurobehavioral contributions to resiliency and/or adaptability of engaging positively in social interactions, tolerance, and awareness (e.g., affiliation, attachment). Cellular and molecular biomarkers related to social systems (e.g., oxytocin) will reveal changes in the underlying neurobiological systems as a function of social support, before, during, and after being in an ICC/ICE environment. Individual differences in indicators of resilience measured before isolation will predict reported loneliness, higher perceived social support, and healthier social neurobiological systems. Individual differences in emotional regulation will provide the most robust evidence for how the neural circuitry moves up to behavior and social processes in self-report and interactions as well as downward toward cellular/molecular biomarkers (e.g., cortisol, BDNF, oxytocin, etc) with structural changes revealed by the fMRI.
Biomarkers of human performance optimization (Dr. Nindl’s Lab) will be tested prospectively within the Neumayer ICE analog. The extensive biomarker panel, analyzed in three separate isolation analogs, will provide insight to the most pertinent biological signatures of resiliency. This information will help guide the down-selection of biomarkers used in the selection of astronauts mostly likely to maintain health and performance in long-duration exploration missions.
During the Definition Phase of this NSCOR project (10/5/17-4/5/18), a literature review was conducted to select and adapt questionnaires. Selected questionnaires will be administered as screening measures (administered pre-mission), characterization measures (administered pre/post-mission), and/or state-based measures (administered in-mission).
The refinement of the biological biomarkers to be measured by blood, saliva, and urine (as funding permits) and refinement of questionnaires to be administered are vital to prepare for the Study Campaigns in each human analog (Neumayer, ICARUS, and HERA). Furthermore, the Meaningfulness of Work Battery that will be implemented in the analogs is crucial for Specific Aim 4.
References
Lin, F., J. Suhr, S. Diebold, and K.L. Heffner, Associations between depressive symptoms and memory deficits vary as a function of insulin-like growth factor (IGF-1) levels in healthy older adults. Psychoneuroendocrino, 2014. 42: p. 118-123
Beste, C., Baune, B. T., Falkenstein, M., & Konrad, C. (2010). Variations in the TNF-a gene (TNF-a-308G-->A) affect attention and action selection mechanisms in a dissociated fashion. Journal of neurophysiology, 104(5), 2523-2531
Hodes, G. E., Pfau, M. L., Leboeuf, M., Golden, S. A., Christoffel, D. J., Bregman, D., ... & Labonté, B. (2014). Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proceedings of the National Academy of Sciences, 111(45), 16136-16141
van Zuiden, M., Kavelaars, A., Vermetten, E., Olff, M., Geuze, E., & Heijnen, C. (2015). Pre-deployment differences in glucocorticoid sensitivity of leukocytes in soldiers developing symptoms of PTSD, depression or fatigue persist after return from military deployment. Psychoneuroendocrinology, 51, 513-524
Valkanova, V., Ebmeier, K. P., & Allan, C. L. (2013). CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. Journal of affective disorders, 150(3), 736-744
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Abstracts for Journals and Proceedings
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Roma PG, Schneiderman JS, Landon LB, Whitmire AM, Williams TJ. "Overview of NASA Behavioral Health & Performance Standard Measures." Presentation at the annual meeting of the 89th Aerospace Medicine Association Meeting, Dallas, TX, May 6-10, 2018. Aerospace Medicine and Human Performance. 2018 Mar;89(3):218. , Mar-2018
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Abstracts for Journals and Proceedings
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Landon LB, Roma PG, Whitmire A. "Team-Level Effects of Sleep and Fatigue: Wake Up, Researchers!" Presentation at the 33rd Annual Conference of the Society for Industrial and Organizational Psychology, Chicago, IL, April 19-21, 2018. 33rd Annual Conference of the Society for Industrial and Organizational Psychology, Chicago, IL, April 19-21, 2018. , Apr-2018
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Abstracts for Journals and Proceedings
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Roma PG, Schneiderman JS, Landon LB, Whitmire AM. "Overview of NASA Behavioral Health & Performance Standard Measures." Poster presentation at the 2018 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2018. 2018 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2018. , Jan-2018
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Abstracts for Journals and Proceedings
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Roma PG, Schneiderman JS, Landon LB, Whitmire AM, Baskin P, Arias DP. "Overview of the NASA Behavioral Health & Performance Laboratory." Poster presentation at the 2018 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2018. 2018 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2018. , Jan-2018
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Abstracts for Journals and Proceedings
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Dinges DF, Basner M, Bilker WB, Gur RC, Hensch T, Nindl BC, Roma P, Stahn AC, and the NSCOR Investigative Group. "NSCOR for Evaluating Risk Factors and Biomarkers for Adaptation and Resilience to Spaceflight: Emotional Valence and Social Processes in ICC/ICE Environments." 2018 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2018. 2018 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2018. , Jan-2018
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