Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training

Britta K Hölzel,J David Creswell,Dieter Vaitl,Tim Gard,Carl Schwartz,Kirk Warren Brown,Douglas N Greve,Sara W Lazar,Lisa Feldman Barrett,Elizabeth A Hoge

doi:10.1016/j.nicl.2013.03.011

Abstract

Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patients with a current DSM-IV GAD diagnosis were randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala–prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala–prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements.

Highlights

Generalized anxiety disorder (GAD) is characterized by pervasive and intrusive worry (American Psychiatric Association, 2000), and is associated with impairment in daily functioning
We explored whether 1) GAD patients would show altered amygdala responses to angry and neutral faces compared with healthy participants, 2) GAD patients receiving the Mindfulness Based Stress Reduction (MBSR) intervention would show greater attenuation in amygdala response compared to the control intervention, 3) GAD patients receiving MBSR would show a greater increase of prefrontal activation, as well as stronger increases in amygdala–prefrontal functional connectivity, compared to the control intervention, and 4) changes in brain activation and functional connectivity would be related to reduced anxiety symptoms
The group comparison of amygdala activation between GAD patients and healthy participants at baseline revealed no significant difference in response to angry faces

Summary

Introduction

Generalized anxiety disorder (GAD) is characterized by pervasive and intrusive worry (American Psychiatric Association, 2000), and is associated with impairment in daily functioning. Mindfulness-based interventions, which focus on the cultivation of attention to present moment experiences with an attitude of openness and non-judgmental (Bishop et al, 2004; Kabat-Zinn, 1990), directly address such deficits. They have been shown to effectively ameliorate anxiety symptoms (Hofmann et al, 2010), and have been successfully applied in the treatment of GAD (Hoge et al, in press; Roemer et al, 2008). The neural mechanisms underlying the effects of mindfulness-based interventions on GAD have not been studied

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Conclusion