Massage for GAD: Neuroimaging and clinical correlates of response

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GAD is a disorder of increased emotional reactivity, with its cardinal symptom, persistent worry, comprising an avoidance mechanism that decreases emotional reactivity to contrasting negative emotions. Evidence-based research has shown that both cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitor antidepressants are efficacious treatments for GAD; however, there is a need for additional acceptable, and widely available treatment approaches for patients suffering from GAD. Massage is a multi-billion dollar industry and in 2016-2017, over 47.1 million adult Americans received at least one massage. Massage is commonly used to increase the overall sense of wellbeing and decrease anxiety and our group has investigated the impact of Swedish massage therapy (SMT) on psychiatric symptoms and physiology. In a 6- week study of twice-weekly SMT vs a light touch (LT) control for GAD, SMT caused statistically significant decreases in anxiety and depression - demonstrating that SMT is biologically active and can impact symptoms of anxiety. Although imaging results in GAD remain inconsistent reduced functional connectivity (FC) within the corticolimbic circuit (amygdala, anterior cingulate cortex (ACC), prefrontal cortex (PFC)) is one of the most consistent findings. At this time there are no brain imaging studies investigating the impact of any type of whole body massage on brain function. The overall goal of this proposal is to identify the neural networks impacted by whole body massage in subjects with GAD. This study is a two-arm, randomized, masked study investigating the effects of SMT vs. LT control on brain activity in subjects with GAD. Medically healthy subjects ≥18 years of age with GAD will undergo fMRI followed by 2/week SMT (n=20) or LT (n=20) for 6 weeks, followed by a second fMRI. Resting state functional connectivity (rsFC) and FC during the fearful/angry faces task will be assessed. Aim 1 is to identify brain networks activated by SMT vs. LT using resting state fMRI and FC during the fearful faces task in subjects with GAD. The primary hypothesis is that relative to the LT control, SMT will result in greater pre-to- post-treatment increase in rsFC between areas known to be altered with anxiety disorders. Second, relative to LT control, subjects undergoing SMT will exhibit less activation in response to the fearful/angry faces task, as well as a greater pre-to-post-treatment decrease in brain activation. Lastly, it is hypothesized that pre-to-post-treatment increases in rsFC will inversely correlate with decreases in changes HAM-A scores, whereas pre-to-post-treatment decreases in brain activation in response to the fearful/angry faces task will be positively correlated with decreases in HAM-A scores within both treatment groups. Completion of this study will provide the first fMRI data evaluating the effects of SMT in comparison to an active control condition, on specific areas of brain connectivity and activity in subjects with GAD.