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

Condition(s) studied

Investigational drug(s) / intervention(s)

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 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,

Study 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.

Eligibility

Primary outcome measure(s)

• 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.

Trial sites (1)

More University Hospital, Strasbourg, France trials in France