Nucleus accumbens volume as a predictor of anxiety symptom improvement following CBT and SSRI treatment in two independent samples


Structural variations of neural regions implicated in fear responses have been well documented in the pathophysiology of anxiety and may play an important role in treatment response. We examined whether gray matter volume of three neural regions supporting fear and avoidance responses [bilateral amygdala, nucleus accumbens (NAcc), and ventromedial prefrontal cortex (PFC)] predicted cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitor (SSRI) treatment outcome in two independent samples of patients with anxiety disorders. Study 1 consisted of 81 adults with anxiety disorders and Study 2 included 55 children and adolescents with anxiety disorders. In both studies, patients completed baseline structural MRI scans and received either CBT or SSRI treatment. Clinician-rated interviews of anxiety symptoms were assessed at baseline and posttreatment. Among the adult sample, greater pre-treatment bilateral NAcc volume was associated with a greater reduction in clinician-rated anxiety symptoms pre-to-post CBT and SSRI treatment. Greater left NAcc volume also predicted greater decreases in clinician-rated anxiety symptoms pre-to-post CBT and SSRI treatment among youth with current anxiety. Across studies, results were similar across treatments, and findings were maintained when adjusting for patient’s age, sex, and total intracranial brain volume. We found no evidence for baseline amygdala or ventromedial PFC volume serving as treatment predictors across the two samples. Together, these findings provide promising support for the role of NAcc volume as an objective marker of anxiety treatment improvement that spans across development. Future studies should clarify the specific mechanisms through which NAcc volume exerts its therapeutic effects.

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Fig. 1: NAcc volume and adult anxiety treatment response.
Fig. 2: NAcc volume and youth anxiety treatment response.


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We would like to thank James Swain, M.D., Ph.D., Gregory Hanna, M.D., Elizabeth Koschmann, Ph.D., David Simpson, Ph.D., L.C.S.W., Sucheta Connolly, M.D., and Jennifer Francis, Ph.D. for their help in providing therapeutic services for the current study.

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Burkhouse, K.L., Jagan Jimmy, Defelice, N. et al. Nucleus accumbens volume as a predictor of anxiety symptom improvement following CBT and SSRI treatment in two independent samples. Neuropsychopharmacol. 45, 561–569 (2020).

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