How the brain responds to unfairness in a computer game can predict whether healthy people will report symptoms of depression in the future, reports a new study published online this week in Nature Human Behaviour. This research may lead to a deeper understanding of which individuals run a particular risk of developing mood disorders in response to unfairness.

Previous studies have suggested that the uneven distribution of wealth - economic inequality - contributes to an increase in psychiatric diseases such as depression. However, the mechanism behind this remains unclear.

Toshiko Tanaka and colleagues measured the brain activity of healthy people while they played a computer game in which a virtual partner offered them money. These offers were either fair - the partner and the recipient would walk away with the same amount - or unfair, with the player receiving less or more than half the share. The authors find that, in response to unfair offers, activity in two areas of the brain - the hippocampus and amygdala - is correlated with depressive symptoms at the time of the test. The same measure (activity changes in the amygdala and hippocampus in response to unfair offers) is also correlated with changes in depressive symptoms between the time of the study and one year later.

In people with strong prosocial values (in this context, people who are averse to all forms of inequality), the authors were able to predict changes in depressive symptoms from the brain response towards all unfair offers - including offers that benefited the participants. This research, conducted on healthy people who did not suffer from clinical levels of depression, highlights that how people respond to inequity has far-reaching implications for their mood. Future research can build on these results to develop ways to identify and protect individuals at risk for mental illness.

In an accompanying News & Views, Megan Speer and Mauricio Delgado write: “The thought-provoking work by Tanaka and colleagues provides an appealing approach to explore these questions and highlights potential risk factors that can precipitate or exacerbate the debilitating nature of depression.”