This study will explore the mechanisms of change that are activated when individuals receive a treatment that targets their weakness and the mechanisms activated when the treatment capitalize on their strength. Patients will be assigned to one of two types of psychotherapies in treating people with a major depression disorder, expressive-supportive vs. emotion-focused treatment. Their ability to benefit from treatment based on their pre-treatment levels of insight and emotional processing will be examined. This is a four-month protocol, with a 2 year follow up period.

One hundred and twenty-four patients suffering from major depressive disorder will be randomized to participate in 16 sessions of either supportive-expressive therapy or emotion-focused therapy. The two treatments are theorized to differ in their main mechanism of change: supportive-expressive therapy places emphasis on insight as its main mechanism of change, and emotion-focused therapy places emphasis on emotional processing as its main mechanism of change. Both can serve as strength- or weakness-focused treatments, based on the patient's baseline levels of insight and emotional processing. Importantly, this study will employ multiple complementary methods, which will include session-by-session self-report questionnaires from both patient and therapist, as well as interdisciplinary measures based on hormonal and acoustic measures, cognitive tasks, clinician interviews, and behavioral coding systems to complement the self-report measures. In addition, prior the beginning of treatment patients will complete diaries via mobile survey application. The findings will contribute to the research on personalized mechanisms of change and can help clinicians focus on more efficient treatment delivery, adapted to given subpopulations of patients, according to their strengths and weaknesses. If a mechanism most likely to stimulate change for a subpopulation is identified, a corresponding treatment can be chosen that is most likely to activate that particular mechanism and by that improve the rate of patients' respondent to treatment.

Inclusion Criteria:

• Meeting major depressive disorder diagnostic criteria using the structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders-5 and scoring more than 14 on the 17-item Hamilton rating scale for depression at two evaluations (one week apart) (Hamilton, 1967).
• If on medication, patients' dosage must be stable for at least three months prior to entering the study, and they must be willing to maintain stable dosage for the duration of treatment
• Age between 18 and 65
• Hebrew language fluency
• Provision of written informed consent.

Exclusion Criteria:

• Current risk of suicide or self-harm
• current substance abuse disorders
• current or past schizophrenia or psychosis, bipolar disorder, or severe eating disorder requiring medical monitoring
• history of organic mental disease
• currently in psychotherapy

Data will not be shared due to ethical reasons.

Double Blind (participants, outcome assessor)