I think mattail has the right idea. I have, like him, experienced the same thing, but not to the degree you describe. I researched the hell out of it and found that this behavior is a known "issue" with Thunderbird/Mozilla.
It seems to revolve around the index file in your profile becoming corrupted, and usually manifests itself once you get a "significant" number of email in a folder (for me, that was around 3700).
The recommended "workarounds" don't really resolve the issue, but will correct the situation once this starts to happen, and involve deleting the offending index file (not the message file!), and letting Thunderbird/Mozilla recreate it. There is a lot of discussion on this on the mozillazine website.
FWIW, I have gotten the problems to become a "non issue" by keeping my "inbox" relatively empty of messages (I "move" them into other storage folders regularly) which seems to be less taxing on the indexing system and seems to keep the file from being corrupted. This presumes, of course, that you have a "clean" index (per the preceeding paragraph) to start with. Of course, YMMV.
It is and irritation, but I still prefer Thunderbird