NASA Human Research Program Investigators' Workshop (2012) 4119.pdf THE IMMUNE SYSTEM AND PSYCHONEUROENDOCRINE SYSTEM UNDER CONDITIONS OF LONG DURATION MISSIONS A .P. Salam1,2, M. Orr3 1 Department of Infectious Diseases and Tropical Medicine, North West London NHS trust ([email protected]), 2 formerly IPEV/ESA, Concordia Station, Dome C, High Antarctic Plateau, 3 Auckland University, New Zealand Objectives To develop a putative complex adaptive system model of links between the immune system and psychoneuroendocrine system. Explore how this model could provide a framework for related behavioural health and performance research in the context of long duration missions (LDM). Background/Motivation There is increasing understanding of the human body as a complex adaptive system, with a range of interactions and feedback mechanisms between the subsystems. Our understanding of the human immune and psychoneuroendocrine systems and their interactions is still limited, however there is an emerging recognition of the complex bidirectional impact of the systems on one another. Methods The putative model was developed via a formal literature review and search of grey literature, augmented by selected domain expert interviews. Results There is a relatively well established literature on the impact of stress and a range of mental disorders (including depression, anxiety and psychosis) on the immune system, particularly around suppression or impairment, of the immune system. However there is also newly emerging evidence and theories around the impact of immune system activation on human psychoneurological function; particularly in the area of pro-inflammatory cytokines triggered by physical illness contributing to the development of depression and anxiety syndromes. Discussion and implications for theory and practice As we look to the International Space Station acting as an analogue for future LDM, developing shared conceptual models of the challenges and opportunities we face should be a core imperative. A model can be useful for communication, shaping and stimulating thought, highlighting strengths and predicting gaps in our knowledge and subsequently guiding future research and development of countermeasures. Our nosological classification of Mental disorders typically operate at the syndromal level with the understanding that multiple different pathophysiological and bio-psycho-social etiological processes may lead to the same syndrome, but we still have limited current understanding of what these processes might be. The bidirectional interactions and feedback between the immunological and psychoneuroendocrine systems remains a significant opportunity gap in our current knowledge particularly the impact of immune responses and related fight-flight responses on the development of mental disorder and related performance impairment. Psychoneuroendocrine responses to infection and injury such as heightened fear and anxiety, withdrawal and irritability make evolutionary sense as evolved and adapted mechanisms to protect the organism from further attack at times of increased susceptibility. We still have a relatively limited understanding of how the human body may interpret the impact or sequelae of space radiation or microgravity, or indeed crowding, leadership issues, interpersonal conflict, as an attack or threat on the system and trigger an immune or fight-flight or stress response that contributes to the development of mental disorder. These are the types of questions or gaps that the emergent putative model would predict as potentially important for future LDM research.