The Butterfly Effect

Everything's perfect in Ponyville. A little too perfect to be true, almost as if it was only the quiet before the storm. And then it is suddenly shattered. Five previously oblivious ponies each receive a note on their door that ruins everything. After that, everything spirals downhill and within a year, Twilight finds herself left with nothing but memories of her beloved friends.

Applejack commits suicide for mysterious reasons, casting a dark cloud of guilt over her friends.

Fluttershy develops an eating disorder and even stops speaking for a while. It gets to the point where the idea of eating sickens her, and getting out of bed is a chore.

Rainbow Dash spends every morning at Fluttershy's bedside, and when she still has free time she starts to lose it. Rainbow takes on as many extra shifts as possible to keep herself too busy to think, and starts to function on less than two hours of sleep. It would be less if it weren't for the worries of a certain pink friend of hers.

Pinkie Pie starts to believe that faking a smile is the new norm. She works so hard to make everyone happy she forgets what being happy is like. The only time she ever hoped to relax is ruined when her weekly playdate with Dashie becomes a daily struggle to keep her best friend from neglecting her needs.

Rarity watches as her closest friends fall apart and quite literally cry themselves to death. Pretty soon she's the only one left, aside from the immortal princess who couldn't die if she tried. She and Twilight are forced closer and closer together, until Rarity wakes up one day and realizes the bookish pony is her best and only friend. She has completely lost contact with the world outside the bubble that is her relationship with Twilight. The moment Rarity ventures out into society once more and finally starts to put her life back together, she is diagnosed with a terminal illness. Little is known about it other than the fact that it can end in nothing but death.