Self Neuro-modulation Therapy for Major Depressive Disorder (MDD) With Anhedonia

The study is comprised of the Screening Visit, Baseline Assessment, Pre-training Visit, 20 NF Training Visits (two training visits per week over 10 weeks), two Booster NF Training Visits (Week 16, and Week 20, and the 3-Month Follow-up Assessment Visit (Week 24).

Participants will receive 20 NF sessions.

The study will test the following hypothesis:

• H0: M(Anhedonic)RS-EFP = M(Anhedonic)Sham-EFP
• H1: M(Anhedonic)RS-EFP ≠ M(Anhedonic)Sham-EFP

Where:

M(Anhedonic)RS-EFP and M(Anhedonic)Sham-EFP are the mean changes from baseline HDRS-17 score in the Active and Sham arms of the Anhedonic MDD participants.

*HDRS-21 is administered for cluster analysis

Inclusion criteria

• Primary Diagnosis of MDD with Anhedonia, established according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text Revision (DSM5TR) - HDRS-17 score of ≥20, SHAPS-C score of ≥25.
• Fluency in written and spoken English.
• Able intellectually to understand the instructions
• Ability to give signed, informed consent either written or electronic (via REDCap eConsent).
• Normal or corrected-to-normal vision and hearing.
• Ability to adhere to the study schedule.
• Completed at least one antidepressant treatment course at an adequate dose and duration in the current episode per the ATRQ.

Exclusion criteria

• Contraindications to MRI (e.g., metal in the body, claustrophobia).
• Any suicidal behavior in the past 1 year (i.e., actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior) assessed using Columbia -Suicide Severity Rating Scale (C-SSRS) prior to screening and during the screening period.
• Diagnosis for current moderate or severe substance or alcohol use disorder (SUD/AUD) within the past month (as defined in DSM-5-substance use disorder).
• Any unstable medical condition, as per the clinical judgement of the investigator.
• Any change in, or initiation of, fluoxetine within the past 8 weeks or of other SSRIs/SNRIs antidepressants, bupropion, stimulants, or other psychiatric medications within the past 4 weeks.
• Recent initiation (within the past 2 months) of psychotherapy; continuation of established maintenance supportive therapy will be permitted.
• Enrollment in another therapeutic clinical study at screening or within 2 months prior to screening or intended enrollment within the duration of this study.