There is an urgent need for novel and effective interventions for treatment-resistant depression (TRD). In previous studies, ketamine has been shown to rapidly reduce depressive symptoms; however, the exact mechanisms of action of ketamine remain unknown. There are some preliminary findings to suggest that ketamine may exert its antidepressant effects through promotion of neurogenesis in the dentate gyrus. The aim of this study is to help delineate the neurocognitive effects of ketamine exposure using a behavioral task (specifically, a pattern separation task) and a battery of other well-established cognitive measures.

This is an assessment-only study, as we will be recruiting subjects to complete an assessment battery at two time points, before and after receiving ongoing ketamine administrations for at least four weeks.

Inclusion Criteria:

1. be 18-80 years old
2. be able to read, understand, and provide written informed consent in English,
3. meet criteria for a current moderate/severe (> 14 on QIDS-SR) depressive episode (unipolar or bipolar mood disorder),
4. have a history of > 3 failed antidepressant trials, and be
5. be seeking ketamine ongoing treatment through the ketamine clinic at Massachusetts General Hospital and be deemed appropriate for the clinic.

Exclusion Criteria:

1. Subjects who will not provide consent to neuropsychological testing
2. Subjects who are not deemed appropriate for the ketamine clinic will not be enrolled

Eligibility for participants includes those ages 18-80 years old who meet criteria for a moderate/severe (as indicated by a score of > 14 on the QIDS-SR) depressive episode (unipolar or bipolar mood disorder), have a history of at least three failed antidepressant trails, and are seeking non-research ketamine treatment through the ketamine clinic at Massachusetts General Hospital (and are deemed appropriate for treatment at the clinic. Participants must also be able to read, understand, and provide written informed consent in English.