Association of Neural Reward Circuitry Function With Response to Psychotherapy in Youths With Anxiety Disorders

Abstract

Objective: Identifying neural correlates of response to psychological treatment may inform targets for interventions designed to treat psychiatric disorders. This study examined the extent to which baseline functioning in reward circuitry is associated with response to psychotherapy in youths with anxiety disorders.

Methods: A randomized clinical trial of cognitive-behavioral therapy compared with supportive therapy was conducted in youths with anxiety disorders. Before treatment, 72 youths (9-14 years old) with anxiety disorders and 37 group-matched healthy comparison youths completed a monetary reward functional MRI task. Treatment response was defined categorically as at least a 35% reduction in diagnostician-rated anxiety severity from pre- to posttreatment assessment. Pretreatment neural activation in the striatum and medial prefrontal cortex (mPFC) during monetary wins relative to losses was examined in relation to treatment response.

Results: Responders, nonresponders, and healthy youths differed significantly in mPFC activation to rewards versus losses at baseline. Youths with anxiety exhibited higher mPFC activity relative to healthy youths, although this may have been driven by differences in depressive symptoms. Planned comparisons between treatment responders (N=48) and nonresponders (N=24) also revealed greater pretreatment neural activation in a cluster encompassing the subgenual anterior cingulate cortex and nucleus accumbens among responders.

Conclusions: Striatal activation to reward receipt may not differentiate youths with anxiety from healthy youths. However, higher striatal responsivity to rewards may allow youths with anxiety to improve during treatment, potentially through greater engagement in therapy. Function in reward circuitry may guide development of treatments for youths with anxiety.

Trial registration: ClinicalTrials.gov NCT00774150.

Keywords: Anxiety Disorders; Child/Adolescent Psychiatry; Neuroimaging; Psychotherapy.

Figures

Figure 1

Results from a one-way ANOVA comparing treatment responders, non-responders, and healthy youth. Youth with anxiety exhibited greater pre-treatment mPFC activation to monetary wins vs. losses relative to healthy comparison youth (p<.005 voxel-wise threshold group differences in extracted parameter estimates are plotted for illustration purposes.>

Figure 2

(A) Left: Treatment responders exhibited greater pre-treatment sgACC/NAcc activation to monetary wins vs. losses compared to non-responders (p<.005 voxel-wise threshold). Group differences in extracted parameter estimates (means) are plotted for illustration. (B) Right: Adding healthy youth to analyses revealed that treatment responders and healthy youth as a group show greater baseline activation in a spatially similar sgACC/NAcc region to monetary wins vs. losses compared to non-responders (p<.005 voxel-wise threshold). Group differences in extracted parameter estimates (means) are plotted below; healthy youth and responders were included as one group in analyses but are plotted separately for illustration.