The longest consecutive amount of time anyone has spent in space was roughly 438 days. That's a long time to be up there, and a mission to Mars and back could take even longer, leaving astronauts alone, in confined spaces, deep in the reaches of the cosmos.
But prolonged isolation is, to put it simply, not always great for humans. According to the book Space Psychology and Psychiatry, long duration space travelers have reported depression, abnormal weakness and loss of energy. Another major problem in long term space travel is something termed the "third quarter phenomenon". In the book Spacefaring: The Human Dimension, space missions are described as occurring in distinct periods.
The first is characterized by excitement and anxiety about the mission ahead. During the second, boredom begins to set in alongside depression. But after the halfway point, astronauts are prone to increased aggressiveness and emotionality, and this can ultimately ground a mission.
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ESA: Mars 500: Study Overview
Research Gate: Personality Characteristics and Trait Clusters in Final Stage Astronaut Selection
Space.com: How Long Does It Take to Get to Mars?