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When worry may be good for you: Worry severity and limbic-prefrontal functional connectivity in late-life generalized anxiety disorder.

  • Wu, M1
  • Mennin, D S2
  • Ly, M1
  • Karim, H T1
  • Banihashemi, L1
  • Tudorascu, D L3
  • Aizenstein, H J4
  • Andreescu, C5
  • 1 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • 2 Teachers College, Columbia University, New York City, NY, USA.
  • 3 Department of Internal Medicine, Graduate School of Public health, Pittsburgh, PA, USA; Department of Biostatistics, Graduate School of Public Health, Pittsburgh, PA, USA.
  • 4 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
  • 5 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: [email protected]
Published Article
Journal of affective disorders
Publication Date
Oct 01, 2019
DOI: 10.1016/j.jad.2019.07.022
PMID: 31357162


Late-life generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older adults. However, its neural markers have received relatively little attention. In this study, we explored the association between worry severity and limbic-prefrontal connectivity during emotional reactivity in late-life GAD. We recruited 16 anxious (GAD) and 20 non-anxious (HC) older adults to perform the faces/shapes emotional reactivity task during functional magnetic resonance imaging (fMRI). We investigated the functional connectivity of both the amygdala and the bed nucleus of stria terminalis (BNST) with the prefrontal cortex (PFC) using generalized psychophysiological interaction (gPPI) analysis. We tested for (1) group differences in connectivity, (2) association between worry severity and connectivity, and (3) interaction between group and worry severity and its association with connectivity. Amygdala-PFC and BNST-PFC functional connectivity were associated with worry severity in an inverse U-shape, and was independent of depression severity, global anxiety, neuroticism, and general cognitive function. Our limitations include slightly skewed PSWQ distributions, lack of non-anxious individuals with high worry, small sample size, and low depression comorbidity in a sample of late-life GAD that may not generalize to GAD in younger populations. This suggests that moderate worry is associated with maximum engagement of the limbic-PFC connectivity, while severe worry is associated with failure of the limbic-PFC emotional regulation circuit. This may explain the aberrant and exaggerated responses to negative stimuli observed in participants with pathological worry. Copyright © 2019. Published by Elsevier B.V.

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