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

Am J Psychiatry. 2021 Apr 1;178(4):343-351. doi: 10.1176/appi.ajp.2020.20010094. Epub 2021 Jan 21.


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: NCT00774150.

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

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anxiety Disorders / diagnostic imaging
  • Anxiety Disorders / physiopathology
  • Anxiety Disorders / psychology
  • Anxiety Disorders / therapy*
  • Brain / diagnostic imaging*
  • Brain / physiopathology
  • Child
  • Cognitive Behavioral Therapy / methods*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / physiopathology
  • Depression / psychology
  • Female
  • Functional Neuroimaging
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Nucleus Accumbens / diagnostic imaging
  • Nucleus Accumbens / physiopathology
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / physiopathology
  • Psychotherapy / methods
  • Randomized Controlled Trials as Topic
  • Reward*
  • Treatment Outcome

Associated data