A new study published in NeuroImage: Clinical has found that certain patterns in the brain related to excessive self-blame are important for predicting the outcome of treatment in depression patients who haven’t responded well to standard treatments.
Only about half of the patients with major depressive disorder (MDD) respond to antidepressant treatment, and a significant number of patients fail to achieve remission even after multiple treatment attempts. The new study sought to identify neural markers related to self-blame in MDD and understand their associations with treatment outcomes. By uncovering these markers, the researchers hoped to improve the personalized treatment of MDD and potentially predict the course of the illness for individual patients.
“This study was based on our previous work on brain networks underpinning excessive self-blame in major depressive disorder,” explained study co-authors Roland Zahn (a professor of mood disorders and cognitive neuroscience) and Diede Fennema (a KCL/IDOR Pioneer Science Fellow), who are both affiliated with the Centre for Affective Disorders at King’s College London and the NIHR Maudsley Biomedical Research Centre.
Their earlier findings showed that people in remission who would go on to experience another depressive episode over the next year had excessive correlation between signals in two brain regions when exposed to self-blaming sentences compared to sentences evoking anger or blame towards others.
“We had previously shown that signal correlations between these brain regions reflected integrating information about the social meaning of a situation (represented in the right anterior temporal region – just beneath one’s temple) and information relevant to the finger of blame (represented in the subgenual frontal region),” the researchers told PsyPost.
“We had also shown that one can use fMRI neurofeedback (brain training) to help people with depression reduce this excessive correlation, but that people with anxious depression did not benefit from this. So, we realised that we needed to understand the relevance of our brain signature of excessive self-blame better in people with current longer lasting forms of depression that had not responded well to treatments.”
“This is because anxious depression is often associated with a longer course of depression and poorer response to standard treatments. This was the goal of Diede Fennema’s MRC-funded PhD and was addressed in the current study for the first time. We registered our study predictions and analysis plans prior to analysing our data to guard against fishing for significant results and biases.”
The researchers recruited 34 participants from the Antidepressant Advisor trial (ADeSS) and through online advertising. Participants were included if they met the criteria for MDD, were currently experiencing a major depressive episode, had moderately severe depressive symptoms, and were non-responders to at least two serotonergic antidepressant medications. Fifteen age- and gender-matched control participants without a history of MDD were also recruited.
The participants received four months of standard treatment from their primary care providers. Before their medication review, they completed an fMRI task involving the presentation of written statements describing actions against social and moral values, where the agent was either the participant (self-agency condition) or their best friend (other-agency condition).
The researchers analyzed the brain scan data using a method called psychophysiological interaction analysis. They focused on the connectivity between a specific brain region called the right superior anterior temporal lobe (RSATL) and another region of interest known as the posterior subgenual cortex (BA25), which is associated with self-blaming emotions compared to other-blaming emotions. Change in depressive symptoms were measured around 14-18 weeks after enrolling in the study via the Quick Inventory of Depressive Symptomatology.
The researchers found that increased connectivity between the RSATL and the BA25 during self-blaming emotions was associated with better clinical outcomes. This means that people with stronger brain connections related to self-blame were more likely to see improvements in their depression during the four-month follow-up period. This suggests that this specific neural signature may serve as a treatment target and can potentially be modified to improve outcomes in MDD.
“As we had predicted, the brain signature of high recurrence risk in fully remitting forms of depression also indicated a higher chance of remission from current symptoms over the next four months in the current study,” Zahn and Fennema told PsyPost. “Our brain signature was not associated with the severity of depressive symptoms and therefore we think it may reflect a more stable way of brain organization in some people, which may render them more vulnerable to a higher number of episodes of depression, but also full remission between episodes.”
“In the past, this was thought to be the case of so-called ‘melancholic’ depression. German Psychiatrist Tellenbach described a melancholic type of personality which he thought was associated with high functioning outside of depressive episodes and so this paradox of higher number of episodes but functioning well between episodes has been described before.”
“We were very nervous about the outcome of this study, because our prediction was highly speculative and had we not pre-registered it, no one would have believed our finding as based on a prior prediction. We were very excited about it.”
However, the researchers also emphasized that while the result was significant, it wouldn’t be enough to predict individual improvements with certainty. The brain signature seemed to predict spontaneous recovery that might have occurred without any treatment, as most participants didn’t change their treatments during the study.
“This means that one cannot say what type of treatment would have been useful to shorten the depressive episode in our study as other groups have done in conjunction with a clinical trial,” the researchers told PsyPost.
More research is needed to understand if this brain pattern is a long-term trait or if it changes with the different stages of depression and how treatments can influence it.
“We are working on combining this brain signature with other information to allow for individual predictions and decision support in the future. Diede Fennema has received funding for postdoctoral fellowship from the IDOR Pioneer Science Initiative in Brazil to study how self-blame-related brain networks change after developing a recurrent episode by comparing with a previous fMRI scan in recovery.”
The study, “Self-blame-selective hyper-connectivity between anterior temporal and subgenual cortices predicts prognosis in major depressive disorder“, was authored by Diede Fennema, Gareth J. Barker, Owen O’Daly, Suqian Duan, Ewan Carr, Kimberley Goldsmith, Allan H. Young, Jorge Moll, and Roland Zahn.
