The primary aim of the study is to determine whether adjunctive intranasal insulin will exert an antidepressant effect when compared to placebo in adults with major depressive disorder (MDD), insufficiently responsive conventional antidepressants. There are three secondary aims of the study (1) to determine whether adjunctive intranasal insulin will alter emotional processing (i.e., cognitive-affective interface); (2) to determine whether early changes in emotional processing (i.e., after a single dose at 40IU intranasal insulin) predicts symptomatic improvement at study endpoint; and (3) to determine the effect of intranasal insulin on neurocognitive performance (e.g., learning and memory). This initiative represents a proof-of-concept study that insulin is important to depressive symptoms, neurocognitive functioning, and emotional processing deficits in MDD, representing a novel and safe therapeutic avenue.