Study suggests mood problems may change brain’s regret sensitivity.

The Icahn School of Medicine at Mount Sinai found that the brain’s processing of regret may affect stress tolerance and psychiatric diseases like depression.

The study, published October 19 in Science Advances, found that mice are sensitive to two types of regret, which presumably originate in different brain regions. A genetic marker that predisposes maladaptive stress response features and depression was connected to sensitivity to one type of regret, while healthy and stress-resilient animals were sensitive to a second type.

These innovative discoveries may impact psychiatry, psychology, and behavioural economics and help develop targeted mood problem treatments for people.

The Mount Sinai study extends rodent models of mental diseases by showing that rats and mice may understand regret-like sentiments. The authors used advanced behavioural economics and chronic stress techniques with viral gene therapy to examine the neurological and molecular foundations of complicated decision making in animals.

This strategy was based on neuroeconomics, which studies how brain limitations affect decision-making. This approach allowed researchers to capture how complex previous choices might affect future decisions and how the way people process or understand missed opportunities can combine with affective states to influence future choices—the basis of regret.

In “Restaurant Row,” mice navigated a maze to find their lone food supply (see animation). Mice had a limited amount of time each day to invest in rewards of varied costs (delays randomly determined from 1 to 30 seconds signalled by the pitch of a tone) and subjective value (unique flavours tied to four separate locations, or “restaurants”). Cost and flavour determined whether mice entered each establishment. If mice accepted an offer by entering the restaurant, they had to wait through a countdown to earn the prize before going on to the next restaurant. Mice showed consistent willingness to wait by restaurant flavour. A decision policy breach might lead to regret.

The study found two distinct types of regret, each associated with a different brain region based on the missed opportunity. Both include animal blunders. However, type one regret was a “economic infraction” in which animals passed up a good opportunity only to fail later (see summary figure). Type two regret occurred when animals wasted their time on unaffordable offerings. Thus, type one regret involves realising that one missed a good chance, but type two regret involves deciding to move on. Type one regret focuses letting something good go, while type two regret emphasises having to modify one’s viewpoint. This study demonstrated that stress-response qualities uniquely influence how these mistakes affect future judgments.

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Journal reference:

Durand-de Cuttoli, R., et al. (2022) Distinct forms of regret linked to resilience versus susceptibility to stress are regulated by region-specific CREB function in mice. Science Advances. doi.org/10.1126/sciadv.add5579.

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