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

Abstract

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.

Figures

Fig. 1

CONSORT flow diagram. Flow diagram showing the progress of participants throughout the trial. SSRIselective serotonin reuptake inhibitors, CBTcognitive behavioral therapy

Fig. 2

Change in brain activation during emotion perception, experience, and regulation pre-to-post treatment. Brain images depict anatomical amygdala, insula, and prefrontal cortex masks used for region-of-interest (ROI) analyses. Line graphs illustrate participant-level changes in activation (gray), as well as mean activation (±standard deviation) pre-treatment and post-treatment for selective serotonin reuptake inhibitors (SSRI; blue) and cognitive behavioral therapy (CBT; red) treatment arms. Notes: dmPFC dorsomedial prefrontal cortex, dlPFC dorsolateral prefrontal cortex, vlPFC ventrolateral prefrontal cortex. Emotion experience and emotion regulation were evoked by the emotional regulation task (ERT). Emotion perception was evoked by the emotional face assessment task (EFAT). *Significant change over time, p < 0.05

Fig. 3

Relation between symptom improvement and brain activation. a Greater anxiety improvement, as measured by the Hamilton Rating Scale for Anxiety (HAMA) total score, was significantly correlated with greater decreases pre-treatment to post-treatment in insula (left) and amygdala (right) activation during emotion perception. b.i Greater depression symptom improvement, as measured by the Hamilton Rating Scale for Depression (HAMD) total score, was associated with greater pre-treatment anterior insula (left) and amygdala (middle) activation during emotion perception. b.ii Greater anxiety symptom improvement, as measured by the HAMA total, was also associated with greater pre-treatment insula (left) and amygdala (right) activation during emotion perception. Shaded region represents bootstrapped 95% confidence intervals