paperhearts thinks Barber's Adagio is both the saddest music ever and also hard to play, or at least, sight-read. I, at age eighteen, would have agreed, at least about the former (for the latter, Chick Corea's La Fiesta was harder). Now, at age whatever, I'd say Aaron Copland's Our Town is the "saddest," or at least most melancholic. Pearl Jam's Small Town is probably next.
Robert on Amazon says Our Town is "moving, surreal, profound."
Eleazar Gutwirth in an abstract for a Jewish Scholarship and Philosophy in the Renaissance conference mentions the 16th century attribution by Amatus Lusitanus of bad diet causing "jewish melancholy." Lusitanus wrote numerous medical case studies:
Following the scholarly practice of his time, Amatus was concerned with the reliability of classical medical texts and distinguished between text, translation and commentaries. He does not care whether a text comes “from the Romans, Arabs or the Christians”; what matters to him is its quality...His medical ethics and his adherence to Judaism are demonstrated in a special oath in the name of the Ten Commandments.