Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disorder and Prediction of Treatment Response
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OBJECTIVE: The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. METHOD: Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. RESULTS: Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. CONCLUSIONS: These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.
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- Authors
- Nitschke, J. B., Sarinopoulos, I., Oathes, D. J., Johnstone, T., Whalen, P. J., Davidson, R. J., & Kalin, N. H.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- American Journal of Psychiatry
- Published
- 2009-03
- Volume
- 166
- Issue
- 3
- Pages
- 302-310
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC2804441
- OpenAlex
- W2124084348
- Cited by
- 375
- References
- 39
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 13 · 2023: 10 · 2022: 15 · 2021: 12 · 2020: 25 · 2019: 17 · 2018: 20 · 2017: 26 · 2016: 30 · 2015: 31 · 2014: 24 · 2013: 28 · 2012: 38
- FWCI
- 44.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CentAUR (University of Reading) (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH074847, P50MH069315, K08MH063984, R01-MH74847, K08-MH63984)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD03352., P30HD003352)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- generalized anxiety disorder, amygdala, anterior cingulate cortex, worry, treatment response prediction, venlafaxine, aversive stimuli, warning signs, neuroimaging biomarkers
- MeSH terms
- Adult, Amygdala, Anxiety Disorders, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Predictive Value of Tests, Surveys and Questionnaires, Severity of Illness Index, Diagnostic and Statistical Manual of Mental Disorders, Young Adult
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