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Open Access Open Badges Short paper

Generalized anxiety modulates frontal and limbic activation in major depression

Michael W Schlund123, Guillermo Verduzco1, Michael F Cataldo12 and Rudolf Hoehn-Saric1*

Author Affiliations

1 Department of Psychiatry, Johns Hopkins School of Medicine, 600 N. Wolfe St., Meyer 4-109, Baltimore MD 21287

2 Kennedy Krieger Institute, 707 N. Broadway, Baltimore MD 21205

3 Department of Behavior Analysis, University of North Texas, PO Box 310919, Denton TX 76203

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Behavioral and Brain Functions 2012, 8:8  doi:10.1186/1744-9081-8-8

Published: 9 February 2012



Anxiety is relatively common in depression and capable of modifying the severity and course of depression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited.


We used functional magnetic resonance imaging and two emotional information processing tasks to examine frontal and limbic activation in ten patients with major depression and comorbid with preceding generalized anxiety (MDD/GAD) and ten non-depressed controls.


Consistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and middle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in MDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the effects varied with the type of emotional information presented.


Our findings highlight frontal and limbic hypoactivation in patients with depression and comorbid anxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional context. One implication of this finding is that divergent findings reported in the imaging literature on depression could reflect modulation of activation by anxiety level in response to different types of emotional information.