Journal
NEUROPSYCHOPHARMACOLOGY
Volume 47, Issue 5, Pages 1081-1087Publisher
SPRINGERNATURE
DOI: 10.1038/s41386-021-01186-0
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Funding
- National Institute of Mental Health [K23 MH106037]
- National Institute of Child Health and Development [R01 HD098757]
- National Institute of Environmental Health Sciences [R01 ES027224]
- Chinese National Natural Science Foundation [81820108018, 81621003, 8202780056, 82027808]
- Chinese Government Scholarship
- Yung Family Foundation
- Functional and Molecular Imaging Key Laboratory of Sichuan Province (FMIKLSP), China
- AbbVie
- Neuronetics
- Lundbeck
- Otsuka
- National Institutes of Health
- PCORI
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The study found that escitalopram can improve emotional processing speed in adolescents with generalized anxiety disorder, with a positive impact on the connectivity of the amygdala to bilateral ventromedial prefrontal cortex and right angular gyrus. Baseline amygdala-vmPFC connectivity and escitalopram-induced increased amygdala-angular gyrus connectivity at week 2 can predict the magnitude of subsequent improvement in anxiety symptoms.
Anxiety disorders are the most common mental disorders in adolescents. However, only 50% of pediatric patients with anxiety disorders respond to the first-line pharmacologic treatments-selective serotonin reuptake inhibitors (SSRIs). Thus, identifying the neurofunctional targets of SSRIs and finding pretreatment or early-treatment neurofunctional markers of SSRI treatment response in this population is clinically important. We acquired pretreatment and early-treatment (2 weeks into treatment) functional magnetic resonance imaging during a continuous processing task with emotional and neutral distractors in adolescents with generalized anxiety disorder (GAD, N = 36) randomized to 8 weeks of double-blind escitalopram or placebo. Generalized psychophysiological interaction analysis was conducted to examine the functional connectivity of the amygdala while patients viewed emotional pictures. Full-factorial analysis was used to investigate the treatment effect of escitalopram on amygdala connectivity. Correlation analyses were performed to explore whether pretreatment and early (week 2) treatment-related connectivity were associated with treatment response (improvement in anxiety) at week 8. Compared to placebo, escitalopram enhanced emotional processing speed and enhanced negative right amygdala-bilateral ventromedial prefrontal cortex (vmPFC) and positive left amygdala-right angular gyrus connectivity during emotion processing. Baseline amygdala-vmPFC connectivity and escitalopram-induced increased amygdala-angular gyrus connectivity at week 2 predicted the magnitude of subsequent improvement in anxiety symptoms. These findings suggest that amygdala connectivity to hubs of the default mode network represents a target of acute SSRI treatment. Furthermore, pretreatment and early-treatment amygdala connectivity could serve as biomarkers of SSRI treatment response in adolescents with GAD. The trial registration for the study is ClinicalTrials.gov Identifier: NCT02818751.
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