Action-adventure game Hellblade: Senua's Sacrifice, which focuses on the main character's battle with psychosis, has been nominated for nine British Academy Games Awards.
The independent game, which focuses on a Celtic warrior affected by the condition, was developed in consultation with neuroscientists and mental health experts in order to properly portray the condition.
Among its nominations are places in the best game and British game categories.
PlayStation exclusive Horizon Zero Dawn has received eight nominations, with adventure title What Remains Of Edith Finch receiving seven.
The Legend Of Zelda: Breath Of The Wild, the launch title for the much anticipated Nintendo Switch console released last year, received five nominations.
All feature in the showpiece best game category, and are joined by Ubisoft's Assassin's Creed Origins and Nintendo's Super Mario Odyssey.
The awards ceremony, which will be hosted by Dara O'Briain, will take place on April 12 in London.
A total of 45 games have been nominated, each "showcasing the very best games of the past 12 months and highlighting an outstanding level of creative excellence from a broad range of UK and international development teams", organiser Bafta said.
As well as its nomination in the best and British game categories, Hellblade's other nominations include places in the artistic achievement, innovation, music, narrative and performer categories.
The awards also feature a new category for 2018 - the game beyond entertainment award - which will recognise games that offer a "transformational experience" beyond just entertainment, Bafta said.
The nominees this year include Life Is Strange: Before The Storm, which tackles issues around love, friendship and bullying.
Also nominated is Night In The Woods, which focuses on depression and the class system in small-time America, and mobile game Bury Me, My Love which is set around a couple separated by the Syrian conflict.
Other games up for awards include Call of Duty: WWII, virtual reality experience Star Trek: Bridge Crew and popular online multiplayer title Overwatch.