Antidepressant short-term and long-term brain effects during self-referential processing in major depression

International audienceAcute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short-and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-2 five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short-and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression

Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice

International audienceChronic stress is known to induce not only anxiety and depressive-like phenotypes in mice but also cognitive impairments, for which the action of classical antidepressant compounds remains unsatisfactory. In this context, we investigated the effects of chronic social defeat stress (CSDS) on anxiety-, social-and cognitive-related behaviors, as well as hippocampal Bdnf, synaptic plasticity markers (PSD-95, Synaptophysin, Spinophilin, Synapsin I and MAP-2), and epigenetic modifying enzymes (MYST2, HDAC2, HDAC6, MLL3, KDM5B, DNMT3B, GADD45B) gene expression in C57BL/6J mice. CSDS for 10 days provoked long-lasting anxious-like phenotype in the open field and episodic memory deficits in the novel object recognition test. While total Bdnf mRNA level was unchanged, Bdnf exon IV, MAP-2, HDAC2, HDAC6 and MLL3 gene expression was significantly decreased in the CSDS mouse hippocampus. In CSDS mice treated 3 weeks with 50 mg/kg/d agomelatine, an antidepressant with melatonergic receptor agonist and 5-HT 2C receptor antagonist properties, the anxious-like phenotype was not reversed, but the treatment successfully prevented the cognitive impairments and hippocampal gene expression modifications. Altogether, these data evidenced that, in mice, agomelatine was effective in alleviating stress-induced altered cognitive functions, possibly through a mechanism involving BDNF signaling, synaptic plasticity and epigenetic remodeling

Resistant depression : potentiation strategies

International audienceLithium is among the most classically recommended add-on therapeutic ă strategy for the management of depressive patients showing unsuccessful ă response to standard antidepressant medications. ă The effectiveness of the add-on strategy with lithium requires achieving ă plasma levels above 0.5 mEq/L. ă Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate ă derivatives or lamotrigine have not demonstrated conclusive therapeutic ă effects for the management of depressive patients showing unsuccessful ă response to standard antidepressant medications. ă Thyroid hormones are considered among the currently recommended add-on ă therapeutic strategy for the management of depressive patients showing ă unsuccessful response to standard antidepressant medications. ă The effectiveness of the add-on strategy with thyroid hormones requires ă achieving plasma concentration of TSH close to the lower limits at the ă normal range (0.4 mUI/L) or even below it. Second-generation ă antipsychotics such as aripiprazole or quetiapine have consistently ă demonstrated significant therapeutic effects for the management of ă depressive patients showing unsuccessful response to standard ă antidepressant medications. ă Second-generation antipsychotics however require the careful monitoring ă of both cardiovascular and metabolic adverse effects

Dépression résistante : les stratégies de changement et d’association de médicaments antidépresseurs

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Quelle définition pour la dépression résistante ?

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Dépression résistante : les autres stratégies thérapeutiques

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