Clinical depression often includes a pessimistic view of things which have happened in the
past and an impairment in the ability to experience pleasure or looking forward to things. A
licensed drug called ketamine affects the levels of glutamate, a chemical messenger in the
brain, and has been used as a treatment particularly for depression which hasn't got better
with other types of medication. Glutamate plays a role in learning and memory so the
investigators are interested in understanding how ketamine can affect how people with
depression remember past negative and positive memories and how they experience reward.
The investigators are conducting a study in depressed participants who did not improve with
the standard antidepressant treatment to expand our understanding on how ketamine can
influence memory, the way people understand emotions and learn from rewards and punishments.
Study participants will undergo medical and psychiatric health screening, drug administration
(ketamine or saline), questionnaires and computer tasks before and after the administration
of the study drug, and an MRI scan after administration of the drug. MRI is a type of brain
scan that allows us to see how the brain responds during for example memories of things which
have happened in the past. This project will help us understand how NMDA antagonists may work
in depression.