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The purpose of this study is to determine the clinical efficacy of augmenting cognitive-behavioral therapy with real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala's response to positive autobiographical memories.

Previous research has shown that real-time fMRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala's response to positive autobiographical memory recall holds therapeutic potential for treating patients with major depressive disorder (MDD), as clinically significant decreases in clinician administered and self-report measures of depression severity were observed following two rtfMRI amygdala neurofeedback sessions. Furthermore, rtfMRI amygdala neurofeedback changed emotional processing towards a positive bias. As this rtfMRI-nf procedure utilizes principles of cognitive-behavioral therapy (CBT), including restructuring thoughts and emotional processing towards the positive, the current study seeks to examine the effects of augmenting CBT with amygdala rtfMRI-nf. Specifically, the investigators plan to test the hypothesis that pretreatment with two amygdala rtfMRI-nf sessions prior to the the start of CBT will result in a higher percentage of patients who exhibit 'sudden gains' (a between session drop of at least 25% on the Beck Depression Inventory associated with better treatment response) compared to those who receive rtfMRI-nf from a parietal control region putatively not involved in emotional processing. Over the course of three years, 60 participants diagnosed with MDD and planning to start CBT will be recruited through the clinical services of the Western Psychiatric Institute and Clinic (WPIC) and through licensed CBT therapists in the Pittsburgh metropolitan area. Participants will undergo two rtfMRI-nf sessions within the two weeks prior to starting therapy. Half of the participants will receive amygdala neurofeedback and half will receive control neurofeedback. At weeks 1-3 and 9 & 10 following the start of therapy, the participant will complete the BDI-II and the NIH Patient Reported Outcomes Measurement Information System (PROMIS) Depression measure. The number of patients who meet criteria for sudden gains and the average session at which this occurred will be compared between CBT + amygdala rtfMRI-nf and CBT + control rtfMRI-nf groups. Success will suggest a new method for improving outcomes to CBT in depressed patients.

Inclusion Criteria:

• right-handed adults
• ages 18 - 55
• primary diagnosis of MDD for recurrent MDD who are currently depressed
• able to give written informed consent prior to participation
• unmedicated OR are stable on an unsuccessful antidepressant regime (at least 4 weeks to ensure symptoms are stable). Effective medications will not be discontinued for the purposes of the study.

Exclusion Criteria:

• clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder
• alcohol and/or substance dependence (other than nicotine) within 12 months prior to screening
• history of traumatic brain injury
• unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g., shrapnel inside body)
• currently pregnant or breast feeding
• unable to complete questionnaires written in English
• current (within 3 weeks of testing) use of any antipsychotics, anticonvulsants, stimulants, benzodiazepines, beta-blockers, or other medications (except antidepressants) likely to influence cerebral blood flow. Effective medications will not be discontinued for the purposes of the study. I
• diagnosis of psychotic or organic mental disorder, bipolar I or II disorder.
• eye problems or difficulties in corrected vision.

10 weeks