The diagnosis of major depression relies on patient reports, and two patients with the same
diagnosis might share only one symptom. Thus, a single mechanism is unlikely to underlie a
broad descriptive diagnosis such as major depression. Our approach is anchored by a neural
circuit taxonomy that proposes distinct biotypes of depression derived from functional
magnetic resonance imaging (fMRI) (Williams et al., 2016). In this study, we aim to target a
putative type of major depression that arises from dysfunction in cognitive control neural
circuitry with a drug called guanfacine.