COMT and post-traumatic stress disorder: For a clinical trial such as is being modeled here, where the primary disease state (PTSD) has itself been suggested to be associated with COMT function (41, 42) and the primary hypothesis being tested is whether biomarkers of catecholamine signaling at baseline are predictive of treatment response, this suggests that the potential for interactive effects between biologic variation in placebo response, disease state, and relevant biomarkers may not be simply theoretical.