The aim of this study is to assess the impact of ketamine on aesthetic perception and processing. This study assesses the role of these effects in facilitating ketamine's antidepressant properties, with a focus on anhedonia. To address this aim, 25 patients with major depressive disorder and 35 healthy controls will be assessed twice with magnetic resonance imaging, once after administration of intravenous ketamine (subanesthetic dose) and once after administration of placebo.This study has a single-center, placebo-controlled, cross-over study design. During MRI, structural, resting state, and functional imaging will be performed. Functional imaging will comprise aesthetic processing, reward, and sexual arousal paradigms. In addition, various neuropsychological scales assessing depressive symptoms, anhedonia, and aesthetic processing will be performed. Eligibility for participation will be assessed during a screening visit, a follow up visit will end study participation.

Inclusion Criteria:

• General health based on medical history and physical examination
• Psychiatric health based on structured clinical interview for DSM-5 (SCID) for healthy controls
• Major depressive episode (first or recurrent) based on structured clinical interview for DSM-5 and ICD-10 for patients
• Age 18 to 55 years
• Right-handedness (due to potential lateralization effects of lefthanded subjects)
• Willingness and competence to sign the informed consent form

Exclusion Criteria:

• Current or history of neurological disease
• Current medical illness requiring treatment
• Psychiatric diagnosis for healthy individuals
• Psychiatric comorbidity with the exception of anxiety disorders for depressed individuals
• Pregnancy or current breastfeeding
• Current or former substance abuse
• Previous ketamine use in lifetime
• Any contraindication for MRI (e.g., MR incompatible implants, etc.) including dental implants causing signal artifacts
• Failure to comply with the study protocol or to follow the instruction of the investigating team