main problem for a manned Mars mission?

The Mars500 project began on 3 June 2009 when three Russians, an Italian, a
Frenchman and a Chinese man entered a sealed experimental facility in Moscow
without access to natural light, fresh air or direct face-to-face contact with
any other human being.For the next 18 months they carried out a battery of daily
duties to [...]
Source:
http://www.ezonearticle.com/2013/01/07/main-problem-for-a-manned-mars-mission/