In the brain, certain nerve cells communicate using a chemical called acetylcholine. Acetylcholine is thought to be important for several functions including mood, memory and wakefulness. The purpose of this study is to explore the role of these nerve cells in depression. Also, we would like to understand how nicotine, the study drug, works in depression and how it affects these nerve cells. To do this, brain imaging will be used before and after this treatment.

Inclusion Criteria:

For Non-Depressed Participants:

• Age range 18 to 65 years old.
• Capacity to consent (able to read, understand, and sign informed consent).

For Participants with MDD

• Age range 18 to 65 years old.
• Capacity to consent (able to read, understand, and sign informed consent).
• Major Depressive Disorder (MDD) as primary diagnosis and currently in a major depressive episode
• Score of at least 29 on the Montgomery-Asberg Depression Rating Scale (MADRS).

Exclusion Criteria:

For Non-Depressed Participants:

• Nicotine use, including tobacco, e-cigarettes, nicotine patch, nicotine gum, within the past year [except for occasional users, who cannot use nicotine products in the week before the scan].
• Need for use of medication during the study that will affect cholinergic levels.
• Problematic drug/alcohol use that is judged sufficient to interfere with study procedures during the treatment period or impact participant safety.
• Significant active physical illness or neurological deficit that may affect brain function or imaging.
• Significant eye conditions such as keratoconus and/or need for rigid contact lenses.
• Current or lifetime history of a major psychiatric diagnosis.
• Any MRI contraindications, including recent tattoos, metal implants, pacemaker, metal prostheses, orthodontic appliances, or presence of shrapnel that are contraindicated for MRI.
• Any PET contraindications, including if study imaging will result in the participant receiving greater exposure than the research limit, or if participant is pregnant, currently breastfeeding, or planning to conceive during the course of study participation.
• Blood donation within 8 weeks of the [18F]VAT scan.

For Participants with MDD

• Nicotine use, including tobacco, e-cigarettes, nicotine patch, nicotine gum, within the past year [except for occasional users, who cannot use nicotine products in the week before the scan].
• Currently on effective antidepressant medications or need for use of medications that target the cholinergic system.
• Problematic drug/alcohol use that is judged sufficient to interfere with study procedures during the treatment period or impact participant safety.
• Significant active physical illness or neurological deficit that may affect the brain function or imaging.
• Significant eye conditions such as keratoconus and/or need for rigid contact lenses.
• Current or lifetime major psychiatric diagnosis other than MDD.
• Life-time history of psychosis or current psychosis.
• Significant risk for suicide.
• Any MRI contraindications, including recent tattoos, metal implants, pacemaker, metal prostheses, orthodontic appliances, or presence of shrapnel that are contraindicated for MRI.
• Any PET contraindications, including if study imaging will result in the participant receiving greater exposure than the research limit, or if participant is pregnant, currently breastfeeding, or planning to conceive during the course of study participation.
• Blood donation within 8 weeks of the [18F]VAT scan.