How A Person Views Sadness Can Predict Depression Relapse

Background
Altered cognitive processing following mood challenge is associated with elevated relapse risk in remitted unipolar depressed patients, but little is known about the neural basis of this reactivity and its link to depressive relapse and prophylaxis.

Methods
Remitted unipolar depressed participants (n = 16) and healthy control subjects (n = 16) underwent functional magnetic resonance imaging (fMRI) while viewing sad and neutral film clips. Correlations were determined between emotional reactivity (neural responses to sad vs. neutral films) in remitted patients and subsequent relapse status over an 18 month follow-up period. A receiver operating characteristic analysis was used to determine signal cutoffs for predicting relapse. Emotional reactivity in relapse prognostic areas was compared between groups.

Results
Within the remitted group, relapse was predicted by medial prefrontal cortical (mPFC; Brodmann's area 32) activity and contraindicated by visual cortical activity (Brodmann's area 17). mPFC reactivity predicted rumination, whereas visual cortical reactivity predicted distress tolerance (acceptance). Compared with control participants, remitted depressed patients demonstrated a more pronounced tradeoff between mPFC and visual cortex reactivity. The difference score between mPFC and visual reactivity yielded excellent prediction of depressive relapse.

Conclusions
Medial prefrontal cortical reactivity to mood provocation in remitted unipolar depressed patients serves as a marker of relapse risk rather than successful emotion regulation. Enduring remission is characterized by normalization of the mPFC to that of healthy control subjects. Furthermore, visual cortex reactivity predicts resilience against depressive relapse, indicating a prophylactic role for sensory rather than ruminative cognitive reactivity in the processing of negative emotion.

From press release:

A University of Toronto study shows that when formerly depressed people experience mild states of sadness, their brain's response can predict if they will become depressed again.

"Part of what makes depression such a devastating disease is the high rate of relapse," says Norman Farb, a PhD psychology student and lead author of the study. "However, the fact that some patients are able to fully maintain their recovery suggests the possibility that different responses to the type of emotional challenges encountered in everyday life could reduce the chance of relapse."

Farb and his team showed 16 formerly depressed patients sad movie clips and tracked their brain activity using functional magnetic resonance imaging (fMRI). Sixteen months later, nine of the 16 patients had relapsed into depression. The researchers compared the brain activity of relapsing patients against those who remained healthy and against another group of people who had never been depressed.

Faced with sadness, the relapsing patients showed more activity in a frontal region of the brain, known as the medial prefrontal gyrus. These responses were also linked to higher rumination: the tendency to think obsessively about negative events and occurrences. The patients who did not relapse showed more activity in the rear part of the brain, which is responsible for processing visual information and is linked to greater feelings of acceptance and non-judgement of experience.

"Despite achieving an apparent recovery from the symptoms of depression, this study suggests that there are important differences in how formerly depressed people respond to emotional challenges that predict future well-being," says Farb. "For a person with a history of depression, using the frontal brain's ability to analyze and interpret sadness may actually be an unhealthy reaction that can perpetuate the chronic cycle of depression. These at-risk individuals might be better served by trying to accept and notice their feelings rather than explain and analyze them."