Clinical depression and the neural circuits for emotion regulation


According to the World Health Organization, clinical depression is one of the leading causes of disability and lost productivity in the world. Understanding the root causes of depression, however, has proved difficult. One topic of great relevance to depression is the neural mechanisms that allow us to regulate our emotions. Although it's normal and healthy for people to have negative emotions in certain circumstances, one of the features of major depression is that they can't pull themselves out of those negative emotional moods. How do the functional workings of the brains of depressed individuals differ from those of healthy individuals when attempting to regulate emotions?

To evaluate the role of emotional regulation in depression, we monitored the brain responses of healthy or depressed individuals to a series of images designed to provoke strong negative emotional responses - images such as car accidents and threatening-looking animals.

Participants were asked to consciously work to decrease their emotional responses to some of the negative images, using techniques such as reframing the meaning of the image, or the context in which it occurred (for example, by telling oneself that the people depicted in a picture of an accident might make a full recovery after treatment). By using this technique, termed cognitive reappraisal, we hope to engage cognitive areas in re-interpreting the emotional content of a stimulus — to either increase or decrease its impact.

In both healthy and depressed individuals, we found that such efforts increased brain activity in prefrontal cortical areas known to help regulate the emotional centers of the brain. However, the striking difference was when we looked at the association between brain activity in the prefrontal cortex, and brain activity in the amygdala, a small almond-shaped structure located deep in the brain that is a key part of the circuitry responsible for generating emotional responses.

In nondepressed individuals, high levels of regulatory prefrontal activity correlated with low activity in the amygdala - in effect, the healthy subjects' efforts successfully quelled their emotional responses. In depressed patients, however, high levels of prefrontal activity were accompanied by high levels of activity in the amygdala.

The difference becomes even more pronounced the harder the patients try. We were  able to gauge the effort made by participants by measuring the degree to which their pupils dilated during the task; more dilation indicates greater effort.

The healthy individuals putting more cognitive effort into regulating their negative emotional responses showed a bigger payoff in terms of decreasing activation in their amygdala. In the depressed individuals, we found the exact opposite relationship - it seems the more effort that depressed individuals put in, the more activation there was in the amygdala.

This finding suggests that healthy people are able to effectively regulate their negative emotions through conscious effort, but that the necessary neural circuits connecting the prefrontal cortex to the amygdala are dysfunctional in many patients with depression.

It is our hope that the results of this and other similar studies may help us progress towards identifying more appropriate treatment methods for people with depression, who represent a diverse patient population. Common psychological therapies use mental strategies similar to those used in this study. It is possible that for some patients at least, perhaps those who show maximal disruption of this prefrontal-amygdala circuitry, psychotherapy might not be as effective as for other individuals for whom the circuitry is functionally more intact.

At this stage, however, such hypotheses remain speculation; a lot more research is needed to put such ideas to the scientific sword, including brain imaging studies that track emotion regulation through different courses of treatment.

Link to the journal article:

Johnstone, T., van Reekum, C. M., Urry, H. L., Kalin, N., & Davidson, R. J. (2007). Failure to regulate: Counter-productive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience, 27, 8877-8884. [PDF]