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.

Anterior cingulate activation to implicit threat before and after treatment for pediatric anxiety disorders.

BACKGROUND: Research suggests that individuals with anxiety have difficulty ignoring threat distractors when completing tasks with competing stimuli. Studies examining the neural correlates of these emotional processing difficulties in youth anxiety highlight reduced recruitment of regions associated with goal-directed attention, such as the anterior cingulate cortex (ACC). In the current study, we examined neural activation during an emotional conflict task in youth with anxiety disorders before and after treatment. METHODS: Twenty-five youth (ages 9-19 years) with generalized, separation, and/or social anxiety disorder and 25 healthy controls underwent 2 functional magnetic resonance imaging scans approximately 13 weeks apart. At each scan, participants completed a task in which they matched shapes in the context of emotional distractors (happy and threatening faces). Between scans, anxious youth were treated with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT). RESULTS: Prior to treatment, anxious youth exhibited reduced activation of the medial prefrontal cortex, encompassing the rostral ACC, when matching shapes in the context of threat distractors relative to healthy controls. Activation in this region increased in anxious youth after treatment, but remained unchanged in the healthy control group. Increases in rostral ACC activation were related to greater reductions in social anxiety and avoidance symptoms following treatment. CONCLUSIONS: Effective treatments for pediatric anxiety may enhance rostral ACC response during attempts to filter out threat-relevant stimuli. Enhanced recruitment of this region may constitute one manner in which CBT and SSRI treatment reduce youth anxiety symptoms, particularly social anxiety and avoidance.