The brains of people with depression, even in remission, respond differently to feelings of guilt, suggesting Freud was right, said researchers from the University of Manchester in the UK who compared magnetic resonance imaging (fMRI) scans of people with a history of depression to those of people who had never had it. If further tests prove successful, they suggest the finding could lead to the first brain scan marker for future risk of depression.

The new study, part-funded by the Medical Research Council was published on 4 June in an online-first issue of the Archives of General Psychiatry.

It is the first piece of research to show there is a brain mechanism behind Freud’s classical idea that depression differs from normal sadness by proneness to exaggerated feelings of guilt or self-blame.

Dr Roland Zahn, from the University’s School of Psychological Sciences, told the press:

“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.”

For their study, Zahn and colleagues took fMRI scans of people while they imagined themselves or their best friend acting badly (eg in a mean, tactless or bossy way) towards others, and said what they felt, for instance, guilt, shame, contempt, or disgust, and whether this was toward self or another.

The participants were 25 people who had been in remission from depression for over a year (16 of whom were not currently taking anti-depressants), and 22 healthy volunteers with no history of depression who served as controls.

Previous studies have suggested that the subgenual cingulate cortex and adjacent septal region (SCSR) become active when we feel guilty, and in healthy people with a low risk of depression, this effect is “selective relative to equally unpleasant feelings associated with blaming others (indignation/anger)”, write the researchers.

The anterior temporal lobe (ATL) has also been consistently implicated in moral feelings such as guilt, but unlike the SCSR, this part of the brain is “activated irrespective of the type of moral feeling, whether it is guilt or indignation”, they note.

There is also evidence to suggest the right superior ATL is important for constructing social concepts that help us make different judgements (eg such as distinguishing merely critical from fault-finding behavior). This in turn protects us against over-generalization and self-blame (eg my pointing out a typing error in a colleague’s piece of writing means “I am critical” as opposed to “I am unlikable”).

So, prior to this latest study, it had already been proposed, but not shown, that a coupling between these two brain areas, or “ATL-SCSR functional coupling”, helps people with low risk of depression blame themselves in an “adaptive” way, without damaging their self-worth or hating themselves.

Zahn and colleagues found the fMRI scans showed the coupling between these brain regions was weaker in the group with a history of depression than in the healthy controls with no history of depression.

“We corroborated the prediction of a guilt-selective reduction in ATL-SCSR coupling in MDD [major depressive disorder] vs controls … and revealed additional medial frontopolar, right hippocampal, and lateral hypothalamic areas of decoupling while controlling for medication status and intensity of negative emotions,” they write.

They also found that lower levels of ATL-SCSR coupling were linked with higher scores on a validated measure of overgeneralized self-blame.

“Interestingly, this ‘decoupling’ only occurs when people prone to depression feel guilty or blame themselves, but not when they feel angry or blame others,” explained Zahn.

“This could reflect a lack of access to details about what exactly was inappropriate about their behaviour when feeling guilty, thereby extending guilt to things they are not responsible for and feeling guilty for everything,” he suggested.

Zahn and colleagues suggest the finding is important because it shows there are brain mechanisms that may explain why some people respond to stress with depression rather than aggression.

The team is now testing whether these findings can predict the risk of depression following remission. If they succeed, this could lead to the first fMRI marker for risk of future depression.

Written by Catharine Paddock PhD