Differential engagement of cognitive control regions and subgenual cingulate based upon presence or absence of comorbid anxiety with depression

Lisanne M. Jenkins, Jonathan P. Stange, Katie L. Bessette, Yi Shin Chang, Samantha D. Corwin, Kristy A. Skerrett, Víctor G. Patrón, Jon Kar Zubieta, Natania A. Crane, Alessandra M. Passarotti, Daniel S. Pine, Scott A. Langenecker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Major depressive disorder (MDD) and anxiety disorders are highly comorbid, sharing many similar symptoms, including impairments in cognitive control. Deficits in cognitive control could be a potential mechanism underlying impaired emotion regulation in mood disorders. Methods: Participants were 44 individuals with no history of mental illness (healthy controls, HC), 31 individuals in the remitted state of MDD (rMDD), and 18 individuals who met lifetime DSM-IV-TR criteria for rMDD and an anxiety disorder in remission (Comorbid). Participants completed a Parametric Go/No-Go (PGNG) test during fMRI. Event-related analyses modeled activity for cognitive control successes (Hits for Targets, Rejections for Lures) and failures (Commissions on Lures) on the PGNG task. Results: The rMDD group showed significantly reduced activity within the cognitive control network (CCN) during Commission errors, including the middle frontal gyrus and inferior parietal lobule (IPL). The Comorbid group showed significantly reduced activity in several clusters within the CCN during correct Rejections, including the left IPL and right inferior frontal gyrus and greater subgenual cingulate. Notably, during correct Rejections, 60% of activation for the Comorbid group was within the Salience and Emotion Network (SEN), with 0% within the CCN. Limitations: The size of the Comorbid subgroup was modest, preventing subanalysis of the different AD subtypes. Conclusions: There is evidence that CCN activity declines in rMDD and that there may be compensatory SEN activity in individuals with Comorbid rMDD and anxiety. Our findings support the identification of comorbid anxiety as a meaningful subtype of MDD that may obscure group differences between rMDD and HCs.

Original languageEnglish (US)
Pages (from-to)371-380
Number of pages10
JournalJournal of Affective Disorders
StatePublished - Dec 1 2018
Externally publishedYes


  • Cognitive control network
  • Compensatory error monitoring
  • Executive control
  • Remitted depression
  • Salience network
  • fMRI

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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