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.

This study is a randomized study. 80 subjects with MDD will be randomly assigned (1:1) to immediately receive 8 weeks of CCBT or delayed treatment, consisting of up to 4 weeks of waitlist, followed by 8 weeks of CCBT. 50 healthy controls of similar age/sex will be recruited to serve as a comparison group for baseline magnetic resonance imaging (MRI) scanning.

The study will enroll subjects for approximately 4 years (~2 subjects per month for 48 months). The length of subject participation will vary based on what group the participants are randomized to. Healthy controls will participate for approximately 8 weeks. Subjects with MDD who were randomized to Early CCBT will participate for approximately 8 weeks; subjects with MDD who were randomized to Late CCBT will participate for approximately 12 weeks. Variability in the study duration for each group depends on each subjects' personal availability for visits and the availability of the magnetic resonance scanner.

Potential participants will complete a phone screen to determine eligibility. If the individual is eligible, the individual will be scheduled for an in-person screening visit. Information collected during the phone screening will not be used in the data analysis; phone screening information will be collected and retained in REDCap. Remote contact options are available as needed/possible.

Screening Visit - all participants will have the study described to them in detail, including the risks and study procedures as outlined in the informed consent form and will sign the informed consent form (ICF) and HIPAA authorization, prior to any study procedures being completed. Participants will be screened for symptoms of psychological disorders and severity of major depressive symptoms by a trained research team member.

If determined eligible, HEALTHY CONTROLS will be scheduled for return to complete an fMRI scan and baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The HIPAA-compliant phone app Beiwe and actigraph setup will take place during the baseline visit. Participants will complete mood monitoring questions on the phone app and also have their activity levels monitored by the phone app and the actigraph for the duration of the study.

If determined eligible at screening, MDD (EXPERIMENTAL GROUP) participants will be randomized (1:1) as follows: One half of the depressed participants will be randomized to receive 8 weeks of CCBT immediately after completing pretreatment assessments and the remainder will be randomized to a waitlist of up to 4 weeks followed by 8 weeks of CCBT.

MDD, EARLY CCBT GROUP Early CCBT participants will be scheduled for return to complete an fMRI scan at the baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The phone apps Beiwe and Ethica and actigraph setup will take place during the baseline visit. Participants will complete mood monitoring questions on the phone apps and also have their activity levels monitored by the phone app and the actigraph for the duration of the study. Participants will complete Good Days Ahead (GDA) computer training throughout the 8 weeks of CCBT, and having 6 encounters with a licensed psychologist/psychiatrist. Additionally, outcome measures will be assessed by an independent clinical evaluator (without knowledge of treatment assignment) every other week. As soon as can be arranged after Week 9 of CCBT treatment (last CCBT Clinical Contact), participants will return to complete an fMRI scan and end of study visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.

MDD, LATE CCBT GROUP Late CCBT participants will be scheduled for return to complete an fMRI scan and baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The phone apps Beiwe and Ethica and actigraph setup will take place during the baseline visit. During the 2-4 week waitlist phase, participants will complete mood monitoring questions on the phone apps and also have their activity levels monitored by the phone app and the actigraph.

At the conclusion of the waitlist of up to 4 weeks, participants will complete a second fMRI scan and complete self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.

Participants will then enter the CCBT phase and will complete Good Days Ahead (GDA) computer training throughout the 8 weeks of CCBT. They will have 6 encounters with a licensed psychologist/psychiatrist at multiple time points during this period. Additionally, outcome measures will be assessed by an independent clinical evaluator (without knowledge of treatment assignment) every other week during this study phase. At Week 9 of CCBT treatment (last CCBT Clinical Contact), participants will complete a 1-hour fMRI scan and self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.

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 130 subjects for this clinical trial.

Inclusion Criteria:

1. Adults 18 - 60 years old, gender inclusive
2. Willing to not take psychotropic medications for the duration of the study
3. Fluent in English (both verbally and written)
4. Able and willing to provide consent
5. Has reliable access to a private computer or electronic tablet
6. Owns a smart phone (iPhone or Android) with ability to download apps

Experimental group 1) Diagnosis of MDD, experiencing current episode as determined by SCID-5 2) Current major depressive episode of moderate severity, as determined by MADRS score of 20 or higher

Control group 1) No history of MDD in lifetime 2) No indication of current, significant depressive symptoms, as determined by MADRS score of 8 or lower

Exclusion Criteria:

1. Diagnosis of severe or poorly controlled concurrent medical disorders that may cause depression or require medication that could cause depressive symptoms
2. Unwilling to provide informed consent
3. Diagnosis of concurrent DSM-5 (SCID) psychiatric disorders: any psychotic or organic mental disorder, bipolar disorder, active alcohol or drug dependence, primary anxiety disorder or primary eating disorders (primary refers to the diagnosis associated with the most functional impairment)
4. Diagnosed (DSM-5 criteria) by the clinical coordinator with attention deficit hyperactivity disorder, learning disorder, borderline personality disorder, antisocial personality disorder, or paranoid personality disorder
5. Cannot complete questionnaires written in English
6. Have not completed at least a 10th grade education or a general education degree (GED)
7. Represent an active suicide risk
8. Centrally acting antiadrenergic agents
9. Have MRI contraindications (e.g., foreign metallic implants, pacemaker, severe claustrophobia)
10. Currently demonstrating a response to antidepressant/psychotropic medication (besides SSRIs, which are acceptable if use has been stable over at least a 2 month period)

Experimental group 1) Score less than 20 on the MADRS at either initial interview or 18 at second interview 2) Have previously failed to respond to a trial of at least 8 weeks of CBT conducted by a certified therapist) 3) Are currently demonstration a response to antidepressant/psychotropic medication besides SSRIs, which are acceptable if use has been stable over at least a 2 month period (individuals taking a psychotropic medication may stop taking it for the purpose of the study ONLY if they are not receiving clinical benefits from taking it and after meeting with one of the study doctors to discuss the risks/benefits of discontinuing the medication and other treatment options)

Control group 1) Must have no lifetime history of a major depressive episode 2) Must score below 8 on the MADRS

3-6 months depending on how long and which group the participant was enrolled in.

An experienced clinical evaluator with established reliability will assess patients pre-treatment and biweekly during CCBT treatment (Weeks 1, 2, 4, 6, 8, 9 of CCBT). All evaluations will be conducted without knowledge of treatment assignment. The evaluator will assess symptom severity according to the MADRS and Hamilton Rating Scale for Depression (HAM-D). Evaluators will have offices remote to the day-to-day operations of the treatment study and will not participate in weekly study management meetings in order to help preserve the blind.