Abstract EN:

Hese deficits coexist in the acute phase of a depressive episode and interfere with decision-making and goal-directed behaviors, and the associated feeling of effort. They appear to persist in periods of clinical remission, decreasing the quality of the therapeutic and functional response and lately worsening the prognosis of the disorder. The aim of this work is to identify objectively measurable neurocognitive markers in clinical practice, and to study their association with the prognosis of a depressive episode, in order to better predict remission and potentially to optimize therapeutic prescribing strategies for patients accordingly. The impairment of neurocognitive processes related to reward constitutes a first vulnerability marker for major depressive disorder (MDD): in a study assessing the production of motor effort in order to obtain a reward, depressed patients had a deficit in production of effort, unlike healthy subjects. Such deficit in incentive motivation - a process underpinned by the activation of ventral cortico-striatal circuits in healthy subjects - may constitute a specific dimension of MDD. It participates in the decision-making and action processes impairments and is associated with – and possibly a consequence of- more specifically cognitive deficits. In a study assessing several cognitive functions in a large cohort of depressed patients, the persistence of psychomotor retardation after 6 to 8 weeks of treatment - in patients considered as being in clinical remission - was positively and independently correlated with the number of past depressive episodes, thus constituting a marker of "cumulative" marker of past depressive episodes. Finally, in a literature review on the progressive evolution of cognitive deficits in MDD, we discussed the existence of a “neurotoxic” effect of the lifetime accumulation of depressive episodes on neurocognitive deficits and its consequences on disease prognosis (increased risk of incomplete functional/clinical remission, relapses, evolution towards dementia). One of the main interest in identifying clinical and cognitive markers of vulnerability is to highlight their capacity to predict the course of a depressive episode-or disorder. In a study based on a cohort of more than 500 depressed patients, a measurement of attention (d2 attention test) was able to significantly and independently predict the subsequent course towards complete remission (clinical and functional) and to constitute a trait -marker of depression, easy to use in clinical practice. Other cognitive markers (such as executive functions) have shown high predictive values for therapeutic response, comparable to those provided by imaging or electrophysiology markers, according to the results of a recent meta-analysis, that emphasizes the interest of using them in patient’s follow-up. Finally, in order to better assess the prognosis of depressive disorder, we have shown that Seasonal Affective Disorder (SAD) diagnosis criteria - which nevertheless represents a specific depressive disorder with well-known physiopathology substrates (construction validity) - had a low predictive validity, prompting to consider this disorder as a temporary expression of a mood disorder, rather than a specific disorder. The identification of clinical tools measuring motivational and cognitive deficits in clinical routine and predicting the course of a depressive episode or disorder represents a major challenge in the improvement of personalized therapeutic management and the long-term prognosis in depressed patients.