Physiological phenotypes and urinary metabolites associated with the psychological changes of healthy human: A study in ‘‘lunar palace 365”

Mental health of the crewmembers is crucial to the success of the task during long-duration space exploration missions, especially in isolated and confined environments. The ability to recognize mental states is essential to effectively help safeguard mental health. However, the current recognition of the mental status is still based on relatively subjective assessment of symptoms as well as psychometric evaluations, lacking objective recognition methods. Fortunately, the “Lunar Palace 365” experiment offers us a precious opportunity to study the objective recognition indicators such as physiological phenotypes and urinary metabolites associated with the psychological changes of crewmembers in isolated and confined environments. In this study, 28 phenotypic measurements were recorded daily. Psychological measurements were completed 1–2 times per week with the symptom checklist 90 (SCL-90) and profile of mood states (POMS) questionnaires, while 24-h urine samples were collected for metabolomics analysis on the day of psychological measurement. Spearman's correlation analysis was performed to identify potential physiological phenotypes and urine metabolic markers associated with mental changes. In this study, all crewmembers showed neither behavioral disturbances nor reports of psychological distress during the 370-day period of mission confinement. Psychological changes showed significant individual differences, but there were consistent and large fluctuations during the mission transitions and when encountering critical events such as power failures and “covering windows”. Crewmembers had lower negative mood scores and higher positive mood scores when they performed their missions the second time than the first. Significant gender differences were found in psychological scores, physiological phenotypes, and urinary metabolites. Spearman correlation analysis showed 11 physiological phenotypes (|R|≥ 0.4, P < 0.001) and 43 urinary metabolites (|R|>0.5, P < 0.001) were significantly associated with psychological changes. Our results provide some potential objective indicators for the diagnosis and evaluation of mental status, and offer more precise guidance for studying the psychological issues of crewmembers during long-term isolation missions in the future.