The purpose of this study is to test whether treatment-resistant late life depression is associated with declines in memory and attention and brain structure and function.

The purpose of this study is to test whether treatment-resistant late life depression is associated with declines in memory and attention and brain structure and function. The study will also test if changes in brain structure and function are associated with decreases in memory. In this study, investigators will conduct a series of assessments/tests, mainly brain imaging and assessments of participant's memory and attention, to better understand how depression is linked to memory and thinking in older persons. Investigators hope that their study will help the scientific community to understand why some people with depressive symptoms that are resistant to treatment in late-life experience declines in their memory and attention and whether effective treatment of such depression reduces that risk. Finally, investigators hope that this study will eventually lead to the development of better treatment options.

Inclusion Criteria:

• Men and women aged 60 and older
• Current Major Depressive Disorder (MDD)
• Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length
• Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher

Exclusion Criteria:

• Dementia
• Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
• High risk for suicide and unable to be managed safely in the clinical trial
• Non-correctable, clinically significant sensory impairment interfering with participation
• Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management.
• Moderate to severe substance or alcohol use disorder
• Seizure disorder.
• Parkinson's Disease
• Individuals with any contraindications to MRI

This study will recruit 750 patient across all 5 sites who are 60 years or older with Major Depressive Disorder. All participants will be recruited from the OPTIMUM trial (clinicaltrials.gov identifier NCT02960763); all participants who consent and are eligible to participate in OPTIMUM will be invited to participate in this neuroimaging/neurocognitive study. Eligibility bellow will be determined and assessed as per the OPTIMUM clinical trial. In addition, they will have no contra-indications for MRI scanning.

A cleaned, complete, and de-identified copy of the final data set including administrative and technical metadata records will be made available on the National Institute of Mental Health (NIMH) Data Archive and registered at clinicaltrials.gov.

Data will become available after all analyses and initial publication is complete.

The data will be accessible through the NIMH Data Archive (Collection ID: 2851). Please contact the principal investigators if you have further queries about access criteria.