Brain Cortical Changes After Major Depressive Disorder Relapse

Investigators sought to determine an association with morphologic brain changes in patients who have relapsed in major depressive disorder.

Patients with major depressive disorder who experience a relapse following recovery show a significant reduction in gray matter volume from baseline to follow-up 2 years later, though patients without relapse show no significant change in volume and an increase in cortical thickness, according to a study published in JAMA Psychiatry.

This longitudinal case-control study sought to identify morphologic brain changes in patients with major depressive disorder who experienced relapse within the first 2 years of recovery and compared those changes to the brains of non-relapsing patients with major depressive disorder. From March 21, 2010, to November 14, 2014, patients experiencing moderate-to-severe depressive episodes recruited from the University of Münster, Department of Psychiatry underwent a magnetic resonance imaging to establish a baseline, then were reassessed 2 years later, from November 11, 2012, to October 28, 2016.

Sixty individuals were divided into 2 groups: those who did experience relapse (n=37, 18 men and 19 women, mean age 37.0 years) and those who did not (n=23, 10 men and 13 women, mean age 32.5 years). A healthy control group (n=54, 30 men and 24 women, mean age 37.5 years) was also included. Relapse was assessed using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. All subjects were matched for sociodemographic and clinical variables, as well as sex, age, educational level, and the time between baseline and follow-up scans.

From baseline to follow-up, participants in the relapse group showed significantly reduced dorsolateral prefrontal volume (−.079; 95% CI, −.113 to −.045; P <.001), and insular volume (−.032; 95% CI, −.063 to −0.002; P =.04). The gray matter of patients in the non-relapsing group did not show a significant difference in volume but did show an increase in cortical thickness. These brain structures are associated with the regulation of emotions.

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This is the first longitudinal study to directly address the brain alterations of middle-aged patients with major depressive disorder before and after relapse. Controls were implemented for confounding variables such as medication, age, severity of depression, familial risk, and childhood maltreatment, but there could be additional confounders such as social support, psychotherapy, and urbanicity. The study was also limited by the fact that the course of illness was assessed and reported by the participants themselves, and so may be less accurate due to recollection biases.

Finding ways to recognize and prevent the kind of negative morphologic changes identified by study investigators may improve the outlook and maintenance treatment experience for future patients with major depressive disorder.


Zaremba D, Dohm K, Redlich R, et al. Association of brain cortical changes with relapse in patients with major depressive disorder [published online March 28, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.0123