This study investigates the relationships and differences in PET-MRI brain imaging biomarkers of abnormal aging and behavioral measures in late life depression compared to healthy controls, and evaluates relationships and differences in the same imaging and behavioral measures following electroconvulsive therapy. The study tests the hypotheses that late-life depression will be associated with higher levels of accelerated aging and brain disease biomarkers, and that electroconvulsive therapy works by stimulating the reorganization of brain tissue.The data collected with contribute to improved knowledge about the neurobiology of late-life psychopathology and its treatment.

This clinical study is a combined single-center, cohort study with a (1) cross-sectional arm evaluating relationships and differences in PET-MR imaging and behavioral measures in 64 patients with late life depression (LLD) compared to 64 healthy controls, and (2) a longitudinal arm evaluating relationships and differences in imaging and behavioral measures in 20 patients receiving ECT as part of their normal clinical management. The study will utilise three PET tracers: (1) [11C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, to estimate synaptic density (2) [18F]MK-6240, which targets tau associated with neurofibrillary tangles, to assess the presence of tau pathology and (3) [18F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain, to assess the presence of cerebral amyloidosis. The main aim of the study is to clarify how hippocampal synaptic density, tau, amyloid and white matter lesions, relate to neuropsychological function, stress and ECT in late life depression.

Inclusion Criteria:

• Diagnosis of late-life depression according to DSM 5 (patients only)
• Age over 60 years old
• Judged to be in good physical health by the investigator on the basis of medical history

Exclusion Criteria:

• history or evidence of psychiatric disease, as assessed by clinical interview (healthy controls only).
• history of major other neurological disorder, or major internal pathology that may make him/her unfit for participation according to the interpretation by the investigator (including cardiac, lung, haematological, gastro-intestinal disorders or cancer);
• current user (including ''recreational use'') of any illicit drugs,including cannabis, or has a history of drug or alcohol abuse;
• had exposure to ionizing radiation (> 1 mSv) in other research studies within the last 12 months;
• has a contra-indication for MRI scanning;
• suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures; cannot lie still for 60 minutes inside the scanner;
• does not understand the study procedures
• unwilling or unable to perform all of the study procedures, or is considered unsuitable in any way by the principal investigator;
• underwent ECT within the last 3 months before enrollment (patients)

A consecutive series of hospital in-patients with late-life depression will be recruited from the Department of Old Age Psychiatry within the University Psychiatric Center, KU Leuven, Belgium. Healthy controls will be recruited from the community by researchers affiliated with the Department of Old Age Psychiatry Department & Translational Neuropsychiatry using traditional means e.g. flyer. All participants will provide written informed consent prior to enrollment in the study in accordance with the Declaration of Helsinki.

The nature of anonymized IPD data that may be made available will be determined on an ad hoc basis and in adherence with the terms of the informed consent provided by the participants and advice from the local ethics committees and university technology transfer office.