Remitted major depression is characterized by reduced prefrontal cortex reactivity to reward loss

J Affect Disord. 2013 Nov;151(2):756-762. doi: 10.1016/j.jad.2013.06.016. Epub 2013 Jul 5.


Background: Major depression (MDD) is characterized by anhedonia. Although a growing body of literature has linked anhedonia in MDD to reduced frontostriatal activity during reward gains, relatively few studies have examined neural responsivity to loss, and no studies to date have examined neural responses to loss in euthymic individuals with a history of MDD.

Methods: An fMRI monetary incentive delay task was administered to 19 participants with remitted MDD (rMDD) and 19 never depressed controls. Analyses examined group activation differences in brain reward circuitry during monetary loss anticipation and outcomes. Secondary analyses examined the association between self-reported rumination and brain activation in the rMDD group.

Results: Compared to controls, the rMDD group showed less superior frontal gyrus activation during loss anticipation and less inferior and superior frontal gyri activation during loss outcomes (cluster corrected p's<.05). Ruminative Responses Scale scores were negatively correlated with superior frontal gyrus activation (r=-.68, p=.001) during loss outcomes in the rMDD group.

Limitations: Replication with a larger sample is needed.

Conclusions: Euthymic individuals with a history of MDD showed prefrontal cortex hypoactivation during loss anticipation and outcomes, and the degree of superior frontal gyrus hypoactivation was associated with rumination. Abnormal prefrontal cortex responses to loss may reflect a trait-like vulnerability to MDD, although future research is needed to evaluate the utility of this functional neural endophenotype as a prospective risk marker.

Keywords: Anticipation; Magnetic resonance imaging; Major depressive disorder; Remission; Reward; Rumination.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / physiopathology*
  • Depressive Disorder, Major / psychology
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Motivation
  • Prefrontal Cortex / physiopathology*
  • Prospective Studies
  • Reward
  • Young Adult