Chronic Anergic Depression IDentification - Magnetic Resonance Imaging Exploration in the Elderly of Traits Related to Onset

Official title

Identification of Trait Markers Differentiating Late-onset Depression from Early-onset Depression in Chronic Anergic Depression in the Elderly

Overview

Depression in the elderly, or "late life depression" (LLD), is often considered to be homogeneous, legitimizing standardized treatment. Yet the literature suggests that there are different forms of LLD, with different pathophysiology, course and treatment. Our experience has led us to identify an "anergic" form, marked by adynamia and anhedonia (anergic depression, AnD). Highly represented among LLDs, it readily resists the usual antidepressants, so that its course is often chronic. Thanks to the "Chronic Anergic Depression Open Trial", the investigators were able to show that AnD responds to dopaminergic (DA) molecules. Therefore the invastigators hypothesized a pathophysiology linked to dysfunction of the mesolimbic DA system. However, not all patients would present the same form: two subgroups could be isolated, each contributing equally. The first corresponds to patients for whom the episode is a recurrence, the so-called "early onset depression" (EOD). The first episode occurs at 34 ±16 years of age and is frequently associated with a personality disorder (73%). The index episode usually lasts 6 ±3 years and is typically associated with anxiety (96%). The second group corresponds to the onset of primary depression after the age of 60, known as "late onset depression" (LOD). The index episode occurs at around 71 ±6 years of age, in people with no premorbid personality disorders. The episode is shorter (3 ±1 years) and anxiety is frequent (75%) but less marked. These patients showed a high propensity for a course compatible with synucleinopathies, but often less rapid than that of the classic forms of these diseases. The investigators hypothesize that within AnD, EOD and LOD present different pathophysiologies, and that this difference is observable on functional magnetic resonance imaging (MRI): LOD patients should present a greater reduction in functional connectivity in the mesolimbic system. The investigators make the subsidiary hypothesis that LODs also show a structural alteration observable with other types of MRI measurements, i.e. multiparametric imaging.

Interventions

• Other Functional MRI with EEG per MRI
  2 MRI examinations will be carried out on a Siemens Vida® MRI ( Siemens®, Erlangen, Germany) 3 Tesla. During this study, no MRI examination requires the injection of a contrast agent. Different sequences, according to several acquisition modalities, will be performed during each MRI. The structural sequences (T1 and T2, MPRAGE) will highlight any lesions in the form of atrophies and/or vascular lesions in the participants, also subject to inter-individual differences. The examination will also

Primary outcome measures

• VTA - mesolimbic system functional connectivity [Time frame: Day 1]

Secondary outcome measures (2)

• Perfusion of the mesolimbic system [Time frame: Day 1]
• Perfusion of the mesolimbic system [Time frame: Day 13]

Eligibility criteria

Inclusion criteria

• Patient aged 60 (inclusive) to 90 years (exclusive)
• Patient presenting with active or remitted anergic depression according to the operational criteria of the "Chronic Anergic Depression Open Trial" (1) confirmed by two psychiatrists involved in the study:

• Early Onset Depression (EOD) group: with at least one history of depression before age 60
• Late Onset Depression (LOD) group: no history of depression before age 60
• Patient able to understand the objectives/risks of the research and give informed consent
• Patient affiliated to a health insurance social protection scheme, beneficiary or dependent

Exclusion criteria

• Contraindication to an MRI scan (including claustrophobia)\*
• Psychiatric or organic comorbidity that may interfere with the interpretation of results (e.g. neurovascular disease, psychotic disorder, proven neurodegenerative disease)
• Concomitant treatment that may interfere with the interpretation of results (e.g. interferons, corticosteroids)
• Patient in exclusion period (from a previous or current study)
• Current protective measure (curatorship, guardianship)
• Patient under legal protection \* presence of non-removable ferromagnetic foreign body, prosthesis, pacemaker, defibrillator, neurostimulation device, medications delivered by an implanted pump, vascular clip or stent, heart valve or ventricular shunt, implanted device incompatible with 3 Tesla MRI exam, claustrophobia, epilepsy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06663891 · 9203 · 2024-A02236-41

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗