To the Editor: We are pleased for this opportunity to respond to Dr. Muller. First, we want to clarify any perception that we identified causative relationships between brain changes and antidepressant response; we did not. We described an association between specific brain change patterns and a change in mood state in depressed patients that is common to treatment with either placebo or active medication. It is unfortunate that our concluding hypothesis, not only based on the findings of the study but considered in the context of other published studies examining pharmacological, cognitive, and somatic treatments, should lead to a critique that negates the value of imaging altogether in the study of major depression. Dr. Muller’s comments suggest an underlying bias not consistent with the wealth of available scientific evidence.