Suppose the copilot had a funny turn after the pilot left the cockpit. They are trained to spot the signs and symptoms of decompression sickness and maybe he (wrongly) thought there was decompression elsewhere in the plane and this was why he felt ill.
Decompression, as in a flaw in the fuselage that allows pressure to reduce to ambient at 38,000 feet, isn't hard to diagnose. Eardrums bursting, sudden cold due to adiabatic expansion of the air, and immediate fog would be clues, as well as the gauge on the panel showing the cabin altitude increasing (the cabin pressure is indicated as an equivalent altitude, not directly as a pressure). The noise of decompression would have been heard on the CVR.
He would know he would only have a few seconds to act so maybe he hit the descent button (in case he passed out but would hope to recover conciousness at a lower altitude). He would have also donned his oxygen mask.
But maybe he also made a fatal decision to try and preserve oxygen levels in the cockpit. Maybe he thought he should lock the cockpit door to prevent the crew from opening it and losing his dwindling oxygen stash. Maybe he assumed total resposibility for the plane and assumed the pilot would be unconscious back in the toilet or main fuselage area. So he was the only vital cog in the whole plane.
Closing the door would do absolutely nothing for oxygen levels, and a pilot knows that. The air at altitude is about 80% nitrogen, 20% oxygen, the same as at sea level. The difference is that the pressure is reduced. Closing the door doesn't increase the pressure. Your lungs require a certain minimum partial pressure of O2 in order to keep the blood oxygenated. When the overall atmospheric pressure is reduced, the way the partial pressure of O2 is maintained is through the use of the oxygen mask, and the way it increases the concentration of oxygen delivered to your lungs.
His oxygen would be delivered by the tank in the pilot's O2 system, regardless of whether the door was open or closed. The system is certified to keep two pilots breathing for far longer than needed to make the descent. With one pilot absent, it would last twice as long, and would be very much more than sufficient.
Furthermore, the pilot has memorized the checklist for use in case of sudden decompression (pilots are required to consult and use a written checklist for procedures which they do every single day, but they must have memorized the checklists for procedures which probably won't be needed during an entire career.) The decompression checklist does not include locking the cabin door.
But then he passed out for real and this would explain his total silence from then on.
But he wouldn't pass out if he had the O2 mask on. He also wouldn't pass out if there had been no genuine decompression, and the evidence suggests no genuine decompression. Finally, the CVR indicates the sounds of people banging on the door to try to break it down, and people screaming. If the air were insufficient for a seated pilot to maintain consciousness, it would be much less sufficient for someone standing and moving around, with the kind of exertion required to bang on the door like that.
Otherwise, someone disturbed enough to commit an act like this would surely be muttering 'something' in their final moments. Maybe not "goodbye cruel world" but maybe some depressed rambling with a few obscenities thrown in?
There's probably a few flaws in the above but maybe there is a similar scenario that fits the evidence better. It just seems so odd that he would just sit there quietly and not speak at all for the whole episode... 
How can you predict the behavior of "someone disturbed enough to commit an act like this?". Do such disturbed people always act rationally and predictably?
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