Novel Neural Circuit Biomarkers of Major Depression

The purpose of the study is to learn more about computer-assisted cognitive behavioral therapy or "CCBT" and to examine connections in the brains of patients with depression. CCBT is approved by the FDA as a form of treatment for depression. It is done partly on the computer and partly with a therapist. This study will enroll participants with depression and participants without depression. The investigators will recruit a total of 100 participants: 80 with Major Depressive Disorder (MDD) and 50 matched comparison participants. Healthy control subjects will participate for approximately 8 weeks. All MDD participants will receive CCBT. Half of the MDD participants will all receive computer-augmented skills training with the Good Days Ahead (GDA) protocol immediately (Early CCBT). Early CCBT subjects will participate for approximately 8 weeks. The other half of the MDD participants initially will be randomized to a waitlist of up to 4 weeks and subsequently will receive CCBT treatment (Late CCBT). Late CCBT subjects will participate for approximately 12 weeks. All participants are asked to complete a screening, which includes a series of clinical interviews and self-report questionnaires about the individual's thoughts, moods, and behaviors. All participants are asked to wear an actigraph, which is a watch-like device that measures activity levels. Additionally, participants are asked to completed short questions and have their activity levels monitored through phone app(s). All participants (Healthy Control and MDD participants) will receive functional magnetic resonance imaging (fMRI) scanning at baseline. Early CCBT participants will receive fMRI scanning after 8 weeks of CCBT, and Late CCBT participants will receive fMRI scanning at the conclusion of the waitlist and after the 8-week course of CCBT. Brain activity will be compared between MDD and controls at baseline and between Early CCBT vs Late CCBT. The 2nd and 3rd brain scans of Late CCBT participants at the end of the waitlist and 8-week course of CCBT, respectively, will allow within-subject comparison of CCBT vs Waitlist treatment effects. This clinical trial has two IRB protocol numbers: 826910 and 832295. The data collected through both protocol numbers will be analyzed together to accomplish the target of 100 subjects for this clinical trial.