Given its huge reliance on patients self-reporting their symptoms and then doctors interpreting those symptoms, diagnosing depression is far from a simple undertaking. Breakthroughs in neuroscience are continuing to shine a light on how this mental health disorder operates, including the revelation of distinctive markers that may make it much simpler to diagnose. New research further adds to this understanding by highlighting how certain brain activity may be linked to certain moods, raising the prospect of a biological signature that could one day be used as an indicator of the illness and help those devising new therapies to treat it.

The research was carried out by neuroscientists at the University of California, San Francisco, and involved monitoring the brain activity of human volunteers for seven to 10 days. More specifically, the subjects were epilepsy sufferers who had 40 to 70 electrodes implanted in their brains as part of routine preparation for surgery to remove scar tissue that triggers seizures.

These electrodes were placed on the brain's surface and also within its deeper structures, and allowed the researchers to track brain activity in regions that earlier research had found to be associated with mood regulation. Meanwhile, the subjects logged their moods on a tablet at regular intervals.

The scientists began their analysis by looking at each subject's long-term recordings of brain activity, on the hunt for what are known as intrinsic coherence networks (ICNs). Likened by the researchers to members of a college band marching in unison, ICNs are sets of brain regions with common activity patterns, meaning that they fluctuate together and at a common frequency. These can be used as indicators of brain regions that are communicating with one another at any one time.

By comparing the brain activity of all the subjects and comparing this to their reported mood data, the team identified some interesting trends. Thirteen of the 21 participants exhibited one common pattern of activity in the brain's hippocampus and amygdala regions, which highly correlated with daily bouts of bad mood or a depressed state throughout the duration of the study. Every one of those subjects had scored highly on a psychological analysis of baseline anxiety ahead of the experiments.

"We were quite surprised to identify a single signal that almost completely accounted for bouts of depressed mood in such a large set of people," says neuroscientist and study author, Vikaas Sohal. "Finding such a powerfully informative biomarker was more than what we'd expected at this stage of the project."

Earlier evidence has linked the brain's hippocampus and amygdala regions with memory and negative emotion. Adding further weight to this line of thinking was the complete absence of these mood-related patterns in the other eight subjects, each of which had much lower levels of pre-existing anxiety going in.

"Based on what we know about these brain structures, this suggests that interactions between the amygdala and hippocampus might be linked to recalling emotional memories, and that this pathway is particularly strong in people with high levels of anxiety, whose mood might then be heavily influenced by recalling emotion-laden memories," Sohal says. "We will need to investigate that hypothesis further, but as a psychiatrist it's deeply satisfying to begin to be able to provide a conceptual framework to patients to help them understand what they are going through when they feel down."

The team has published its research in the journal Cell.