After a handful of days, Sims suffering from the Negative Mood effect tend to be quite unhappy, no matter their surroundings, and as a simple test, saving and exiting to the main menu, then loading back into the game, cures them as soon as game-time resumes.
I haven't noticed anything with room scores - the moods are especially dismal when my Sims are at work or school. Exiting and reloading fixes the problem, but even with the highest-rated beds, and waking my Sims before they get the 'well-rested' moodlet, their moods start to plummet again. The problem gets worse the longer I play without exiting, so whatever is going on, it's cumulative.