Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder

•Higher CRP predicts greater SAD symptom improvement during VR exposure therapy.•CRP, SAD symptoms, and subjective distress all decline during VR exposure therapy.•However, declines in CRP and SAD symptoms are not associated within-persons. Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. CRP decreased over the course of treatment, b = −0.03 (SE = 0.01), p =.02 95 %CI [−0.06, −0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = −0.45 (SE = 0.15), p =.004 95 %CI [−0.74, −0.15], and avoidance, b = −0.62 (SE = 0.19), p =.002 95 %CI [−1.01, −0.23], and in-session subjective distress from pre-treatment to post-treatment, b = −0.42 (SE = 0.21), p =.05 95 %CI [−0.83, −0.001]. However, declines in CRP were not correlated with declines in fear, r = −0.07, p =.61, or avoidance, r = −0.10, p =.49, within-persons. Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.