The ages of anxiety—differences across the lifespan in the default mode network functional connectivity in generalized anxiety disorder

Andreescu, Carmen; Sheu, Lei K.; Tudorascu, Dana; Walker, Sarah; Aizenstein, Howard

doi:10.1002/gps.4051

Cited by 70Functional Brain Connectivity StudiesAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesMental Health Research Topics

The ages of anxiety—differences across the lifespan in the default mode network functional connectivity in generalized anxiety disorder

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Andreescu, Carmen, Sheu, Lei K., Tudorascu, Dana, Walker, Sarah, Aizenstein, Howard·2014·International Journal of Geriatric Psychiatry

DOI 10.1002/gps.4051PMC PMC4028428

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Abstract

OBJECTIVES: Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders, but its neural basis is relatively understudied. This study aims to characterize the functional connectivity in the default mode network (DMN) in GAD across the lifespan. DESIGN AND SETTINGS: Functional and structural magnetic resonance imaging data were collected with subjects at rest. We analyzed the resting state functional connectivity patterns in the DMN for 27 GAD participants and 39 non-anxious comparison participants. Using a two-way analysis of variance, we explored the interaction between age and GAD status on functional connectivity. In GAD participants, we analyzed the correlation of functional connectivity indices with the duration of illness and worry severity. RESULTS: The age-by-anxiety interaction showed a greater anxiety effect on the functional connectivity between the posterior cingulate seed and the medial prefrontal cortex for the older group relative to the younger participants. Longer duration of illness was positively correlated with greater functional connectivity between the posterior cingulate cortex and the insula. Worry severity was inversely correlated with the functional connectivity between the posterior cingulate cortex seed and the medial prefrontal cortex. CONCLUSION: The presence of GAD, longer duration of illness, and more severe worry exacerbate the effects of age on the functional connectivity in the DMN. These results support the need for tailored research and interventions in late-life anxiety.

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fMRI studies of worry have shown increased connectivity between default mode network structures (dorsomedial PFC).
“as well as increased connectivity between default mode network structures (dorsomedial PFC; Andreescu et al., 2014).”
From Neural correlates of emotion acceptance<i>vs</i>worry or suppression in generalized anxiety disorder (2017) · cites this paper as Andreescu et al., 2014
The Results (Voxelwise Regression Analysis; page unavailable) report a significant negative correlation between worry severity and medial prefrontal connectivity, rather than the increased connectivity attributed to this paper. The Discussion likewise describes a negative association between worry severity and ventromedial PFC connectivity; it does not report increased dorsomedial PFC connectivity with worry. (LLM, conf=0.85)
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Andreescu et al. (2014) found that broad scale hyperconnectivity of the insulae was associated with greater GAD severity.
“Similarly, Andreescu et al. (2014) found that broad scale hyperconnectivity of the insulae was associated with greater GAD severity.”
From Distinct functional connectivities predict clinical response with emotion regulation therapy (2017) · cites this paper as Andreescu et al. (2014)
The Results (Voxelwise Regression Analysis) link greater bilateral insula connectivity to longer illness duration, not greater GAD severity. The GADSS severity association was in the frontal lobe and did not survive multiple-comparison correction. The paper therefore does not support the claimed broad-scale insula hyperconnectivity–severity association. (LLM, conf=0.87)
Experimental — accuracy not yet measured
With respect to GAD and MDD, resting state fMRI studies clearly implicate disruption in DN regions.
“With respect to GAD and MDD, resting state fMRI studies clearly implicate disruption in DN regions (e.g., Hamilton et al., 2011, 2013; Chen and Etkin, 2013; Andreescu et al., 2014; Wang et al., 2016).”
From Distinct functional connectivities predict clinical response with emotion regulation therapy (2017) · cites this paper as Andreescu et al., 2014

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The Default Mode Network In Late-Life Anxious Depression
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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, M., Mennin, D. S., Ly, M. J., Karim, H. T., Banihashemi, L., Tudorascu, D., Aizenstein, H. J., & Andreescu, C. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.07.022 · Cited by 16 · see citing works
Dissociable salience and default mode network modulation in generalized anxiety disorder: a connectome-wide association study
Li, R., Shen, F., Sun, X., Zou, T., Li, L., Wang, X., Deng, C., Duan, X., He, Z., Yang, M., et al. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhac509 · Cited by 30 · see citing works
Dysfunction of default mode network characterizes generalized anxiety disorder relative to social anxiety disorder and post-traumatic stress disorder
Yuan, M., Liu, B., Yang, B., Dang, W., Xie, H., Lui, S., Qiu, C., Zhu, H., & Zhang, W. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.04.099 · Cited by 38 · see citing works

Authors: Andreescu, C., Sheu, L. K., Tudorascu, D., Walker, S., & Aizenstein, H.
Affiliations: University of Pittsburgh (US)
Corresponding author: Andreescu, Carmen
ORCID: Andreescu, Carmen
Tudorascu, Dana
Walker, Sarah
Aizenstein, Howard
Venue: International Journal of Geriatric Psychiatry
Publisher: Wiley
Published: 2013-11-20
Volume: 29
Issue: 7
Pages: 704-712
ISSN: 0885-6230 (ISSN-L)
1099-1166
DOI: 10.1002/gps.4051
PMC: PMC4028428
OpenAlex: W1487460843
Cited by: 70
References: 46
Citations by year: 2026: 1 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 11 · 2018: 5 · 2017: 6 · 2016: 1 · 2015: 7 · 2014: 3
FWCI: 2.01
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: International Journal of Geriatric Psychiatry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Siemens Medical Solutions USA
National Institutes of Health (UL1TR000005)
National Institute of Mental Health (MH-071944, R01MH076079, P30MH071944, MH086686, K23MH086686)
National Center for Research Resources (UL1RR024153)
National Center for Advancing Translational Sciences
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
Keywords: generalized anxiety disorder, default mode network, resting-state functional connectivity, lifespan differences, age effects, posterior cingulate cortex, medial prefrontal cortex, insula, disease duration, late-life anxiety, neuroimaging
MeSH terms: Adult, Age Factors, Analysis of Variance, Anxiety Disorders, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Case-Control Studies, Prefrontal Cortex

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The ages of anxiety—differences across the lifespan in the default mode network functional connectivity in generalized anxiety disorder

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