Emotion-based brain mechanisms and predictors for SSRI and CBT treatment of anxiety and depression: a randomized trial

Stephanie M. Gorka*, Christina B. Young, Heide Klumpp, Amy E. Kennedy, Jennifer Francis, Olusola Ajilore, Scott A. Langenecker, Stewart A Shankman, Michelle G. Craske, Murray B. Stein, K. Luan Phan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Mechanisms and predictors for the successful treatment of anxiety and depression have been elusive, limiting the effectiveness of existing treatments and curtailing the development of new interventions. In this study, we evaluated the utility of three widely used neural probes of emotion (experience, regulation, and perception) in their ability to predict symptom improvement and correlate with symptom change following two first-line treatments—selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT). Fifty-five treatment-seeking adults with anxiety and/or depression were randomized to 12 weeks of SSRI or CBT treatment (ClinicalTrials.gov identifier: NCT01903447). Functional magnetic resonance imaging (fMRI) was used to examine frontolimbic brain function during emotion experience, regulation, and perception, as probed by the Emotion Regulation Task (ERT; emotion experience and regulation) and emotional face assessment task (EFAT; emotion perception). Brain function was then related to anxiety and depression symptom change. Results showed that both SSRI and CBT treatments similarly attenuated insula and amygdala activity during emotion perception, and greater treatment-related decrease in insula and amygdala activity was correlated with greater reduction in anxiety symptoms. Both treatments also reduced amygdala activity during emotion experience but brain change did not correlate with symptom change. Lastly, greater pre-treatment insula and amygdala activity during emotion perception predicted greater anxiety and depression symptom improvement. Thus, limbic activity during emotion perception is reduced by both SSRI and CBT treatments, and predicts anxiety and depression symptom improvement. Critically, neural reactivity during emotion perception may be a non-treatment-specific mechanism for symptom improvement.

Original languageEnglish (US)
Pages (from-to)1639-1648
Number of pages10
Issue number9
StatePublished - Aug 1 2019

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology


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