The Course of Disease in Major Depressive Disorder Is Associated With Altered Activity of the Limbic System During Negative Emotion Processing

Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Mar;7(3):323-332. doi: 10.1016/j.bpsc.2021.05.008. Epub 2021 Jun 5.


Background: Brain functional alterations during emotion processing in patients with major depressive disorder (MDD) compared with healthy control subjects (HCs) are frequently reported. However, evidence for functional correlates of emotion processing with regard to MDD trajectories is scarce. This study investigates the role of lifetime disease course for limbic brain activation during negative emotional face processing in patients with MDD.

Methods: In a large sample of patients with MDD (n = 333; 58.55% female) and HCs (n = 333; 60.06% female), brain activation was investigated during a negative emotional face-processing task within a cross-sectional design. Differences between HC and MDD groups were analyzed. Previous disease course, characterized by 2 components, namely hospitalization and duration of illness, was regressed on brain activation of the amygdala, (para-)hippocampus, and insula in patients with MDD.

Results: Patients with MDD showed increased activation in the amygdala, insula, and hippocampus compared with HCs (all p values corrected for familywise error [pFWE] < .045). The hospitalization component showed negative associations with brain activation in the bilateral insula (right: pFWE = .026, left: pFWE = .019) and (para-)hippocampus (right: pFWE = .038, left: pFWE = .031). No significant association was found for the duration of illness component (all pFWE > .057).

Conclusions: This study investigated negative emotion processing in a large sample of patients with MDD and HCs. Our results confirm limbic hyperactivation in patients with MDD during negative emotion processing; however, this hyperactivation may resolve with a more severe lifetime disease course in the insula and (para-)hippocampus-brain regions involved in emotion processing and regulation. These findings need further replication in longitudinal studies.

Keywords: (Para-)hippocampus; Amygdala; Depression; Disease course; Functional magnetic resonance imaging; Insula.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Sectional Studies
  • Depressive Disorder, Major*
  • Emotions / physiology
  • Female
  • Humans
  • Limbic System
  • Magnetic Resonance Imaging
  • Male