Recent research published in JAMA Psychiatry is shedding light on the neural mechanisms behind relapse of major depressive disorder (MDD)—suggesting that focusing on certain neural regions after an episode could help predict the illness’ future course.

Despite major depression’s heavy global presence, the disease still has low rates of remission and high rates of relapse, Mary L. Phillips, MD, wrote in JAMA. 

“Understanding the pathophysiological processes that predispose people to MDD is clearly a step toward identifying objective neural markers that may guide treatment choice and novel intervention developments that can be translated into personalized interventions,” she said. “Yet there has been little focus on understanding neural mechanisms that predispose individuals to relapse.”

Phillips wrote these types of studies could aid in the development of individualized interventions or, in some cases, could halt or prevent relapse in high-risk patients. She cited a longitudinal study conducted by a trio of German scientists as a step forward in attaining such information.

In their study, Phillips wrote, Dario Zaremba, MSc, and colleagues “narrowed the gap” in neuroimaging research with a small-scale study in which they examined whole-brain and region-of-interest changes in gray matter volume and cortical thickness over the course of two years. Sixty MDD patients in total were recruited for the study and matched with 54 control participants.

Zaremba et al. used automated whole-brain voxel-based morphometry to examine gray matter volume in the patients and analyzed regions of interest that focused on changes in cortical thickness. During follow-up, participants were classified as either experiencing no relapse or at least one relapse depressive episode—the majority of the pool, 37 patients, was in the latter group.

“The interpretation of these findings by Zaremba et al. was that a relapsing course of illness in MDD, as opposed to a non-relapsing course, is associated predominantly with gray matter reductions in neural regions implicated in executive function and emotional regulation and salience processing, possibly because of changes in glial cell density or neuronal size,” Phillips wrote.  She said that, importantly, there were no significant links between depressive symptom severity at the study’s baseline, symptom severity at follow-up and medication load on gray matter volumes.

Phillips said the trial is a “first step” in identifying objective neural markers of the future course of MDD, especially in midlife populations.

“The study stands out as important because of its focus on two key clinical problems in MDD, which are the high relapse rate and the difficulty in predicting illness course,” she wrote. “At a broader level, in a climate where the role of neuroimaging techniques in psychiatry remains unrealized, this study highlights the potential real-world utility of these techniques as clinical tools to provide information that can considerably influence long-term treatment choices to improve clinical outcomes for many people with MDD.”