People with a history of depression have brains that respond differently to feelings of guilt compared to the brains of others who never get depressed, according to a study on brain scans.

The study found that patients who had recovered from depression were more likely to show activations in parts of the brain associated with guilt, even when researchers primed them with scenarios where someone else was at fault.

Researchers said that the latest findings, published in the Archives of General Psychiatry, provides the first concrete evidence of brain mechanisms  to explain Sigmund Freud's century-old theory that exaggerated guilt and self-blame are key to understanding depression.

"Our research provides the first brain mechanism that could explain the classical observation by Freud that depression is distinguished from normal sadness by proneness to exaggerated feelings of guilt or self-blame," lead researcher Dr. Roland Zahn of the University of Manchester said in a news release.

"For the first time, we chart the regions of the brain that interact to link detailed knowledge about socially appropriate behavior – the anterior temporal lobe – with feelings of guilt – the subgenual region of the brain – in people who are prone to depression."

Zahn and his colleagues asked 22 healthy people with no history of depression and 25 people who had previously had a major depressive episode and asked him to imagine that they had behaved poorly, like being "stingy" or "bossy" towards their best friend, or that their best friend had acted badly towards them.

Researchers found that people who had previously been depressed were less able to "couple" the brain regions associated with guilt and knowledge of appropriate behavior together as people who had never been depressed, making them less likely to become indignant and blame others when being wronged.

"Interestingly, this 'decoupling' only occurs when people prone to depression feel guilty or blame themselves, but not when they feel angry or blame others. This could reflect a lack of access to details about what exactly was inappropriate about their behavior when feeling guilty, thereby extending guilt to things they are not responsible for and feeling guilty for everything," Zahn said.

Not only will the do the latest findings reveal brain mechanisms underlying specific symptoms of depression, they may also explain why some people react to stress with depression rather than aggression.

Zahn said that people who have people who have previously been depressed are significantly more likely to experience another depressive episode, and understanding the brain’s vulnerabilities may help scientists target new therapies or drug treatments.

Researchers said that they will now work on determining whether brain scans can predict patients' depression risk after remission of a previous episode, and if the unusual activation of the anterior temporal lobe in depressed patients can be unlearned.