Late Life Depression
Conditions
Keywords
Late life depression neuroimaging,, connectivity,, apathy,, dopaminergic system
Brief summary
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
OTHERFunctional 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 involve a quantitative multiparametric acquisition with 8 modalities (R1, R2, Radial and Axial Diffusion in Diffusion Tensor, dispersion, orientation and density index of neurites by NODDI, the Macromolecular Proton Fraction, measurement of magnetic susceptibility and R2\*) to characterize tissue properties. Functional imaging (in resting state, during film viewing and performance of cognitive tasks in ASL, BOLD and multiband) will allow analysis of the primary endpoint - functional connectivity,
Sponsors
University Hospital, Strasbourg, France
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| VTA - mesolimbic system functional connectivity | Day 1 | Functional connectivity, observed at the subpopulation level, between the ventral tegmental area (VTA) and regions of the mesolimbic system (i.e.: ventral striatum and pallidum, amygdala, and subgenual anterior cingulate \[with separate analysis of Brodmann area 25\] and ventromedial prefrontal cortex), obtained by ROI to ROI analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perfusion of the mesolimbic system | Day 1 | Mean cerebral perfusion rates measured by arterial spin labeling (ASL) in regions of interest (i.e.: ventral tegmental area, ventral striatum and pallidum, amygdala, and subgenual anterior cingulate \[with separate analysis of Brodmann area 25\] and ventromedial prefrontal cortex). |
Countries
France
Contacts
CONTACTLudovic DORMEGNY-JEANJEAN Doctor
PRINCIPAL_INVESTIGATORLudovic DORMEGNY-JEANJEAN Doctor
Department of Physiology and Funtional Explorations at Strasbourg University Hospitals
Outcome results
None listed