Clinical depression can zap the pleasure out of an enjoyable meal or the thrill out of winning a prize, among other symptoms. Not surprisingly, a region of the brain involved in reward and motivation, called the nucleus accumbens, has been associated with depression. But up to now, it had been unclear what went wrong with this region in the brains of people suffering from clinical depression.

A study in the December 21 issue of Proceedings of the National Academy of Sciences suggests that the problem is not merely a lack of activity in the nucleus accumbens (NAcc). This region still became activated after depressed participants looked at images associated with positive emotions. But, after looking at a series of both positive and negative images, NAcc activity eventually faded, suggesting that the reward center cannot sustain happiness in depressed people.

To arrive at this finding, a research team led by Richard J. Davidson at the University of Wisconsin in Madison examined the levels of activation in the brains of 27 depressed and 19 healthy individuals via functional magnetic resonance imaging (fMRI). During 37-minute fMRI sessions, participants viewed an assortment of 72 positive images for 10 seconds each. To try to simulate the combination of daily "highs" and "lows" that are typically experienced, the researchers randomly intermixed those 72 images with 72 negative photos. The researchers asked the participants, four seconds into each viewing, either to enhance, suppress or sustain (aka, not change) their response to the image. For example, "in response to a stunning natural scene, a participant might imagine being in that scene or one of their own choosing" to enhance his or her reaction, the authors wrote.

By comparing the results for depressed and control groups within the first and second halves of the 37-minute session separately, the researchers were able to perceive changes in how depressed individuals responded to positive images over time. Initially, there was no difference in the extent to which the NAcc region was activated after the two groups enhanced or simply watched positive images. In the second half of the session, however, the activity in this region plummeted for depressed patients, compared with healthy individuals, after they were asked to enhance or sustain their responses to positive images. There was no difference in the response of the two groups when they were asked to suppress their reactions.

Previous studies on depression have implicated other regions of the prefrontal cortex, which is the region of the brain involved in high-level cognition, in the control of the nucleus accumbens, as well as in the control of both negative and positive emotions. So Davidson's group explored other differences in the activity of the prefrontal cortex in depressed individuals. Using fMRI, the authors found that the activity of a region of the brain that occupies about one-third of the prefrontal cortex, called the middle frontal gyrus, is connected with that of the nucleus accumbens in the control participants. In depressed individuals, however, this connection was lost in the second half of the experiment.

The researchers also connected the activity of the NAcc region with emotions among the depressed group. Over the course of the session, as the level of NAcc activation dropped, so did the level of positive emotion that depressed participants reported they experienced.

"[A] treatment regime which attempts to increase the depressed patient's ability to sustain engagement of the NAcc may ameliorate [depression] symptoms," the authors wrote. In fact, they point out, that one behavioral therapy model instructs patients to increase the amount of time spent doing rewarding activities. This strategy has been effective for some patients and, perhaps now with the additional support from this study, its practice could expand.

Image courtesy of iStockphoto/RapidEye