I've run into this with permissions errors in my home folder.
However, if you're using a SQLite wrapper directly, it's possible it's leaking (as in memory leak) database/connection instances and/or not closing them properly when done, which means new connections are opened in addition each time the database is touched. Get familiar with Instruments (the "Leaks" instrument, specifically) if you're not already, then post the results if you're still stuck.