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High rostral anterior cingulate cortex (rACC) activity has been shown to predict antidepressant treatment response; however, it is unclear whether this is a fixed versus variable marker of responsiveness. The authors measured rACC theta current density in 22 subjects 5 weeks before and again immediately before 5 weeks of blinded treatment with sertraline. Mixed-effects regression analysis found that the relationship between response and rACC activity depended significantly on the timing of the rACC assessment; rACC activity measured immediately before treatment was a significantly better predictor of response. rACC activity may constitute a variable “state” indicator of responsiveness to antidepressants.