Neural correlates of anxious distress in depression: A neuroimaging study of reactivity to emotional faces and resting-state functional connectivity

Laura Nawijn, Richard Dinga, Moji Aghajani, Marie-José van Tol, Nic J. A. van der Wee, Andreas Wunder, Dick J. Veltman, Brenda W. H. J. Penninx

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Background: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. However, little is known about the neurobiological correlates of anxious distress in MDD. Methods: We probed the relation between the DSM-5 ADS and task-related reactivity to emotional faces, as well as resting-state functional connectivity patterns of intrinsic salience and basal ganglia networks in unmedicated MDD patients with (MDD/ADS+, N = 24) and without ADS (MDD/ADS−, N = 48) and healthy controls (HC, N = 59). Both categorical and dimensional measures of ADS were investigated. Results: MDD/ADS+ patients had higher left amygdala responses to emotional faces compared to MDD/ADS− patients (p =.015)—part of a larger striato-limbic cluster. MDD/ADS+ did not differ from MDD/ADS− or controls in resting-state functional connectivity of the salience or basal ganglia networks. Conclusions: Current findings suggest that amygdala and striato-limbic hyperactivity to emotional faces may be a neurobiological hallmark specific to MDD with anxious distress, relative to MDD without anxious distress. This may provide preliminary indications of the underlying mechanisms of anxious distress in depression, and underline the importance to account for heterogeneity in depression research.
Original languageEnglish
Pages (from-to)573-585
Number of pages13
JournalDepression and anxiety
Issue number7
Early online date2022
Publication statusPublished - Jul 2022


  • amygdala
  • anxiety
  • anxious distress specifier
  • depression
  • neuroimaging
  • salience

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