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.
Patient aged 60 (inclusive) to 90 years (exclusive)
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
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)
Parallel
Functional MRI with EEG per MRI
Other intervention2 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,
VTA - mesolimbic system functional connectivity
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.
Perfusion of the mesolimbic system
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).
Perfusion of the mesolimbic system
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).
Quantitative parameters measured in multiparametric MRI in the ventral tegmental area
R1
Quantitative parameters measured in multiparametric MRI in the ventral tegmental area
R1
Θ / β powers ratio
Frequency and maximum intensity of fluctuations in the ratio between the powers in θ and β bands. This analysis aims to allow the localization of the regions associated with fluctuations in vigilance during acquisition. This localization will be allowed by a methodology and analysis parameters already published by our team. The MRI localization maps obtained at the subpopulation level will be compared.
Θ / β powers ratio
Frequency and maximum intensity of fluctuations in the ratio between the powers in θ and β bands. This analysis aims to allow the localization of the regions associated with fluctuations in vigilance during acquisition. This localization will be allowed by a methodology and analysis parameters already published by our team. The MRI localization maps obtained at the subpopulation level will be compared.
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