A preliminary investigation of neural correlates of treatment in adolescents with generalized anxiety disorder
Open accessAbstract
Objective: Generalized anxiety disorder (GAD) is a prevalent and debilitating psychiatric condition of adolescence. Two effective forms of treatment are cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). This pilot study examined changes in brain function following each type of treatment in GAD. Method: Subjects were 14 youths with GAD (7 had CBT, 7 received fluoxetine) and 10 age- and gender-matched healthy peers. Functional magnetic resonance imaging (fMRI) scans were acquired before and after treatment for patients and over two comparable time points for controls. During fMRI acquisition, a probe detection task with emotional (angry, happy) and neutral faces allowed for assessment of neural response to threat. Following previous research, region of interest analyses were performed in the right ventrolateral prefrontal cortex (VLPFC). Results: fMRI results showed increased right VLPFC activation, relative to controls, in the medication ( t (15) = 3.01, p < 0.01) and CBT ( t (15) = 3.22, p < 0.01) groups following treatment. Conclusions: This study shows significant increase in right VLPFC activation in response to angry faces following treatment with CBT or fluoxetine for GAD. This is consistent with previous research indicating that the VLPFC may facilitate effective responding to underlying neural correlates of anxiety in other brain regions, such as the amygdala.
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Psychotropic medications such as SSRIs have been shown to enhance prefrontal down-regulation of the amygdala in healthy controls and depressed patients.
“As psychotropic medications, such as selective serotonin reuptake inhibitors, have been shown to enhance prefrontal down-regulation of the amygdala in healthy controls (Sladky, Spies, et al., 2015) and in depressed patients (Heller et al., 2013; Maslowsky et al., 2010), medication effects are an important consideration for future research on emotion regulation.”
From Changes in functional connectivity with cognitive behavioral therapy for social anxiety disorder predict outcomes at follow-up (2020) · cites this paper as Maslowsky et al., 2010
The fMRI Results (p. 10) report increased ventrolateral prefrontal activation after fluoxetine treatment relative to controls. But the treated participants were adolescents with generalized anxiety disorder, not depressed patients, and the study does not demonstrate prefrontal down-regulation of the amygdala. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn adolescents with generalized anxiety disorder, pretreatment amygdala activation is associated with less clinical improvement, and successful treatment with CBT or fluoxetine is associated with increased right ventrolateral prefrontal activation to angry faces.
“Pretreatment amygdala activation was associated with less clinical improvement after treatment.”
From Neural Substrates of Childhood Anxiety Disorders (2012) · cites this paper as [126]
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- Authors
- Maslowsky, J., Mogg, K., Bradley, B. P., McClure-Tone, E., Ernst, M., Pine, D. S., & Monk, C. S.
- Affiliations
- University of Michigan (US)
- University of Southampton (GB)
- Georgia State University
- National Institute of Mental Health
- National Institutes of Health (US)
- Corresponding author
- Maslowsky, Julie
- Venue
- Journal of Child and Adolescent Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2010-04
- Volume
- 20
- Issue
- 2
- Pages
- 105-111
- ISSN
- 1044-5463 (ISSN-L)
- 1557-8992
- PMC
- PMC2865364
- OpenAlex
- W2012675869
- Cited by
- 125
- References
- 45
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 10 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 10 · 2015: 8 · 2014: 8 · 2013: 11 · 2012: 11
- FWCI
- 13.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Child and Adolescent Psychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (K22MH068017)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- generalized anxiety disorder, adolescents, cognitive behavioral therapy, fluoxetine, selective serotonin reuptake inhibitors, ventrolateral prefrontal cortex, threat response, emotional face processing, amygdala
- MeSH terms
- Adolescent, Anxiety Disorders, Emotions, Facial Expression, Female, Fluoxetine, Humans, Male, Neural Pathways, Pilot Projects, Psychomotor Performance, Visual Perception, Cognitive Behavioral Therapy, Selective Serotonin Reuptake Inhibitors, Prefrontal Cortex
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