Age

40–60

Sex

ALL

Healthy volunteers

Not accepted

1. Age 40-60 years, inclusive.
2. Diagnosis of MDD as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)6 determined through a structured clinical interview.
3. Current major depressive episode of at least 3 months in length.
4. Depression of at least mild severity defined by a total score of ≥7 on the Montgomery Asberg Depression Rating Scale (MADRS)7.
5. Ability to understand and comply with the requirements of the study, as judged by the investigator(s).

1. Presence of comorbid post-traumatic stress disorder, obsessive-compulsive disorder, eating disorder(s), schizophrenia, or other psychiatric disorders.
2. History of a manic, hypomanic, or mixed depressive episode.
3. Treatment with electroconvulsive therapy, intravenous and/or intranasal ketamine in the 6-weeks prior to study enrolment.
4. History of substance-use disorder in the past 12 months.
5. Presence of current alcohol-use disorder
6. A positive urine toxicology screen for non-prescribed substance use.
7. A positive pregnancy test at screening.
8. A history of major medical or neurological illness.
9. A history of traumatic brain injury, stroke, seizures, or previous brain surgery.
10. Contraindications to magnetic resonance imaging (MRI) scanning.

Neuroimaging Markers of Midlife Depression and Cognitive Behavioural Therapy (CBT)