Mental and Cognitive Health Effects of Ketamine on Lateral Habenula Activity in Treatment Resistant Depression

Clinical depression often involves by 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 we are interested in understanding how ketamine can affect how we remember our past negative and positive memories processes. We are conducting a series of studies in both depressed participants and healthy volunteers to improve our understanding on how ketamine can influence memory and the way people learn from rewards and punishments. Study participants will undergo medical and psychiatric health screening, drug administration (ketamine or saline), questionnaires and computer tasks, and MRI scans before and after the administration of the study 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 ketamine may work in depression.