The game pulls no punches when it deals with the theme of depression and suicide.
- Near the end of Chapter 2, Susan is woken up by the chatty and friendly nurse Liz, who begs Susan to follow her to escape the hospital. The exits on the ground floor is guarded, and Liz opts to go to the roof instead. It's shortly revealed that Liz's definition of 'escaping the hospital' is to jump off the roof of the building. Then it dawns on the player that she, just like Susan, is also suicidally depressed. No matter how much the player tries to convince her to stop, even by answering all of her questions correctly, Liz takes a leap and falls to her death. The soundtrack doesn't help, either
. - Zoe's cough and choking sounds as she dies from her rare pollen allergy. Made worse by the fact you can't actually see her and can only listen.
- Susan, seeing the old woman, a.k.a The Queen of Maggots behind Mitzi, tries to warn Mitzi to leave because she thinks Mitzi will die. Mitzi responds by revealing that she is already dying of cancer.
- Susan's mental breakdown in Chapter 3 probably hits a little too close to home to players actually suffering from depression, especially since it's not triggered by any huge traumatic event but a culmination of little annoyances and stressors that she is unable to cope with.
- The Queen of Maggots informs Susan that she is now immortal. Susan's reaction?Susan: This is the last thing I wanted!
- In the final voiceover in one of the endings, it is set sometime after the events of the game, and by that time Mitzi has died.
- Susan and Mitzi's conversation in Flat 1.Mitzi: Mrs. A? ...What does depression feel like?
Susan: Well... It feels like all I want is to die... but I have to live.
Mitzi: That's funny... Most of the time I feel like I want to live... but I have to die. - "Mitzi... Think of a vegetable while I'm gone..."
- The Queen of Maggots informs Susan that she is now immortal. Susan's reaction?
- Fail to calm Susan down in Chapter 3 after escaping from or killing Doctor X, which is notoriously hard to do on the first try and Susan will suffer from a breakdown after being harshly told off by her neighbor for playing the piano late at night. All that hard work to calm Susan down can be all for naught if she is too anxious beforehand, and her breakdown can hit a little too close to home for those who suffer from anxiety and depression.
- The whole of the epilogue, mixed with Heartwarming Moments.
- The endings all count to some degree, while all are a Bittersweet Ending to some degree, some border more on Downer Ending:
- Revenge has Mitzi give Susan the gas mask, leading to Susan killing Adam in her stead, then mourning over Mitzi's decision to sacrifice herself to save Susan's life.
- A Ruthless Killer has Mitzi kill herself by shooting Adam in the gas-filled room, followed by Susan mourning that Mitzi succumbed to Adam's taunting, leaving her behind all alone.
- I Care About You has Mitzi listen to Susan and leave Adam behind peacefully. She soon dies slowly in a hospital of her cancer, though Susan mentions that it was easier since both women knew it was happening.
- The Golden Ending follows I Care About You, but Mitzi survives the cancer. Instead of visiting Mitzi's grave, Susan visits her daughter's grave and starts to feel better thanks to Mitzi's support, but still has to fight daily with her depression.
- Just the final sentence in the endings as "Forever" by Siah/Josiah Orsie starts playing:
Susan: I teach myself to smile again. One day I get better. I know I will. Even if it takes me not nine...but nine hundred lives.
