By Alex Fradera

In recent years, researchers have sought to look under the hood to understand the neural correlates of the changes brought about by psychotherapy. Not only can such understanding help us hone in on the precise processes that are being acted upon in therapy, thus helping us focus on these gains, they could also show where pharmacological interventions might be complementary, and where they could directly obstruct the therapeutic work. Now a systematic review and meta-analysis in Psychiatry Research: Neuroimaging has outlined all we know so far about how therapy changes the depressed brain, and it suggests key changes occur in emotional processing areas.

An international team, led by Cynthia Fu and first-author Anjali Sankar at the Institute of Psychiatry, Psychology and Neuroscience in London and the University of East London, conducted a search of the brain imaging literature, looking specifically for studies that uncovered the brain changes associated with recovery from depression following various forms of psychotherapy, including CBT and psychodynamic psychotherapy.

The 17 papers they gathered hinted at some consistent patterns, such as decreased amygdala activity after therapy when looking at both emotional and more neutral stimuli, but there were also occasional results that were harder to square – for instance one study showed more activation in hippocampal areas while another study found less activation in the very same region. This inconsistency is to be expected for a still-young domain of investigation, especially when different labs are experimenting with different study designs, so shouldn’t be over-interpreted.

Where the review is most valuable is through the use of a meta-analysis of five studies that asked volunteers with depression to look at emotional images in the brain scanner before and after they had undertaken psychotherapy.

This showed that, after CBT, patients with major depression showed less activation in the left precentral gyrus. This area is in the brain’s prefrontal cortex, which is involved in thinking and reflective processes. People who are depressed exhibit more activity in this area during emotional tasks, which appears to reflect their tendency to over-process and ruminate on thoughts and worries. As such, the reduction in prefrontal cortex activity after therapy may indicate the effectiveness of therapy in discouraging such negative cognitive styles – taking things for what they are rather than using them as a springboard into contemplating a worst-case scenario.

Another finding was that, after CBT or psychodynamic psychotherapy, patients showed more activation in the left rostral (pregenual) anterior cingulate (see image above; healthy controls did not show this change, suggesting it was not simply due to the passage of time or practice effects at the image-viewing task). This brain area is strongly connected with core emotion processing regions, including having a suppressing effect on activity in the amygdala. Evidence already suggests that the connections between the anterior cingulate and the amygdala are weaker in major depression, explaining why emotions may feel more overwhelming. So it appears that one of the effects of psychotherapy may be the re-establishment of this damaged connection. The meta-analysis can’t tell us exactly how, but one possibility is through practices such as “cognitive re-appraisal” – finding new ways of interpreting difficult experiences.

Fu and Sankar and the rest of their team emphasise that we’re still in early days of making sense of the relationships between brain changes and clinical response, especially the extent of improvement – for instance, how much does an increase in pleasure in life relate to changes in a particular brain region? They note a study from 2012 that took this approach, finding that extent of improvement on a depression inventory correlated with the activity change in the anterior cingulate cortex, reinforcing that this may be a key brain region worthy of further examination.

For now, we’re still chipping away at the gargantuan task of mapping how the process of therapy plays out in the neural tissue that sits within our skulls. It’s an endeavour worth continuing – as Sankar and colleagues explain, “Understanding the mechanisms of treatments on brain activity has the potential for developing diagnostic biomarkers and identifying new targets for beneficial forms of treatment”.

—A systematic review and meta-analysis of the neural correlates of psychological therapies in major depression

Alex Fradera (@alexfradera) is Staff Writer at BPS Research Digest