Or they have bi-polar disorder and are on a downswing. That alone will do it.
Some forms of depression are medical, people need to be aware of this. Thinking that everyone can be cured by running off and finding one's true self is incredibly dangerous. For some people, that is the solution, but for others, running away from their support network is the exact wrong thing to do.
All that said, soul crushing jobs are soul crushing. The modern world's insistence that we all have true purpose in life has not helped things any. A lot of people used to just be happy getting married, having kids, and seeing their kids do well. Now, we all want some sort of higher purpose (I'm guilty of this as well), which makes obtaining happiness really hard.
For the longest time, success was "at least a few of your kids survived". Since then, standards have been raised to a point that only a fraction of the population can meet the current bar.