Behavioral health risks are among the most serious and difficult to mitigate risks of confinement in space craft during long-duration space exploration missions. We report on behavioral and psychological reactions of a multinational crew of 6 healthy males confined in a 550 m(3) chamber for 520 days during the first Earth-based, high-fidelity simulated mission to Mars. Rest-activity of crewmembers was objectively measured throughout the mission with wrist-worn actigraphs. Once weekly throughout the mission crewmembers completed the Beck Depression Inventory-II (BDI-II), Profile of Moods State short form (POMS), conflict questionnaire, the Psychomotor Vigilance Test (PVT-B), and series of visual analogue scales on stress and fatigue. We observed substantial inter-individual differences in the behavioral responses of crewmembers to the prolonged mission confinement and isolation. The crewmember with the highest average POMS total mood disturbance score throughout the mission also reported symptoms of depression in 93% of mission weeks, which reached mild-to-moderate levels in >10% of mission weeks. Conflicts with mission control were reported five times more often than conflicts among crewmembers. Two crewmembers who had the highest ratings of stress and physical exhaustion accounted for 85% of the perceived conflicts. One of them developed a persistent sleep onset insomnia with ratings of poor sleep quality, which resulted in chronic partial sleep deprivation, elevated ratings of daytime tiredness, and frequent deficits in behavioral alertness. Sleep-wake timing was altered in two other crewmembers, beginning in the first few months of the mission and persisting throughout. Two crewmembers showed neither behavioral disturbances nor reports of psychological distress during the 17-month period of mission confinement. These results highlight the importance of identifying behavioral, psychological, and biological markers of characteristics that predispose prospective cre PLoS One PLoS ONE 440 plosone plos PLoS ONE 1932-6203 PLOS PMC3968121 PMC3968121.1 3968121 3968121 24675720 10.1371/journal.pone.0093298 PONE-D-13-43542 1 Research Article Biology and Life Sciences Ecology Behavioral Ecology Neuroscience Behavioral Neuroscience Neuropsychology Psychology Behavior Human Performance Emotions Psychological Stress Ecology and Environmental Sciences Medicine and Health Sciences Mental Health and Psychiatry Mood Disorders Neuropsychiatric Disorders Physical sciences Astronomical sciences Space exploration Mars Exploration Program Spaceflight Space missions Social Sciences Psychological and Behavioral Changes during Confinement in a 520-Day Simulated Interplanetary Mission to Mars 520d Simulated Mars Mission: Psychological Changes Basner Mathias 1 * Dinges David F. According to NASA [6] , “anecdotal and empirical evidence indicates that the likelihood of a behavioral condition or psychiatric disorder occurring increases with the length of a mission” and “while behavioral conditions or psychiatric disorders might not immediately and directly threaten mission success, such conditions can, and do, adversely impact individual and crew health, welfare, and performance, thus indirectly affecting mission success.” There is a critical need to predict the time course, magnitude, and individual variability in behavioral, cognitive, affective and interpersonal reactions of space explorers during long-duration missions. Materials and Methods 2.1 Subjects and protocol The State Scientific Center of the Russian Federation –IBMP of the Russian Academy of Sciences performed the Mars 500 project at the IBMP in Moscow, which consisted of three isolation studies with six crewmembers each: a 14-day pilot study (completed in November 2007), a 105-day pilot study (completed in July 2009), and the main 520-day study simulating a mission to Mars (completed in November 2011), which is the focus of this The high fidelity of the simulation to actual spaceflight was reflected in the following features of the experiment: (i) a multinational crew of N = 6 healthy adult male volunteers selected by the Russian Federation (N = 3), the European Space Agency (N = 2), and the China National Space Administration (N = 1), who were trained together and who were similar in age (average age at hatch closing 32 years, range 27–38), careers, and education (e.g., engineers, physicians, military backgrounds) to astronauts/cosmonauts living on the ISS; (ii) 520 consecutive days of confinement (3 June 2010 to 4 November 2011) in a 550 m 3 pressurized facility with a volume and configuration comparable to a spacecraft with interconnected habitable modules; (iii) facility modules equipped with life support systems and an artificial atmospheric environment at normal barometric pressure; (iv) activities that simulated aspects of the International Space Station with daily maintenance work, scientific experiments, and exercise; (v) isolation from Earth's daily environmental light-dark cycles, temperatures and seasonal conditions; (vi) a realistic Mars flight simulation based in orbital mechanics and under the direction of mission controllers, with a 30-day Mars orbiting phase (between mission days 244 and 273) and 3 of the 6 crewmembers simulating egresses on the Martian surface (between mission days 257 and 265); (vii) work throughout the 520-day mission that included both routine and simulated emergency events; (viii) changes in communication modes and time delays between mission days 54 and 470 that would occur in transit to and from Mars; (ix) limited consumable resources (food and water); and (x) the crew awareness of frequent publicity of the mission by media and the public. Finally, our protocol was one of at least 90 other protocols carried out in the quasi-operational environment of the 520-day Mars mission simulation. We had no control over the other protocols that may have introduced unexplained variance in our outcome measures.