Search

Major depressive disorder is a complex multifactorial condition with a so far poorly characterized underlying pathophysiology. Consequently, the available treatments are far from satisfactory as it is estimated that up to 30% of patients are resistant to conventional treatment. Recent comprehensive evidence has been accumulated which suggests that inflammation may be implied in the etiology of this disease. Here we investigated ketamine as an innovative treatment strategy due to its immune-modulating capacities. In a murine model of LPS-induced depressive-like behavior we demonstrated that a single dose of ketamine restores the LPS-induced depressive-like alterations. These behavioral effects are associated with i/ a reversal of anxiety and reduced self-care, ii/ a decrease in parenchymal cytokine production, iii/ a modulation of the microglial reactivity and iv/ a decrease in microglial quinolinic acid production that is correlated with plasmatic peripheral production. In a translational approach, we show that kynurenic acid to quinolinic acid ratio is a predictor of ketamine response in treatment-resistant depressed patients and that the reduction in quinolinic acid after a ketamine infusion is a predictor of the reduction in MADRS score. Our results suggest that microglia is a key therapeutic target and that quinolinic acid is a biomarker of ketamine response in major depressive disorder., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: Vascular endothelial growth factor (VEGF) is a key player in the pathogenesis of neovascular age-related macular degeneration (nAMD) and is also involved in the final common pathway of antidepressant medication. This study investigated the relationship between the need for anti-VEGF retreatment in patients with nAMD and antidepressant medication, and the potential impact of ocular structural factors., Methods: Data from two identical prospective 2-year treatment protocols using ranibizumab or aflibercept in a variable-dosing regimen ('Observe-and-Plan') were analysed. Retreatment requirement was compared with antidepressant medication intake (primary outcome) and a variety of ocular factors from baseline and from month 3 response (secondary outcomes), using univariate and multivariate analyses., Results: Of the 206 included patients (227 eyes), 19 were on antidepressant medication. Their nAMD eyes significantly more often had pigment epithelium detachment (PED, p=0.04). Multivariate analysis revealed a significant association between anti-VEGF retreatment requirement and antidepressant medication use (p=0.027), as well as thicker central retinal thickness at month 3 (p<0.0001) and month 3 PED height (p=0.001)., Conclusion: This study provides evidence that treatment with antidepressant medication increases the anti-VEGF retreatment requirement in patients with nAMD, possibly through the interplay of antidepressant medication, depression status and VEGF levels., Competing Interests: Competing interests: IM has served as a consultant and/or speaker for Novartis, Bayer and Allergan, and has received writing support for an independent article from Novartis. OM has acted as consultant for Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche and Servier. RG has received compensation as a member of the scientific advisory board of Janssen, Lundbeck, Roche and Takeda. He has served as consultant and/or speaker for AstraZeneca, Pierre Fabre, Lilly, Otsuka, Sanofi and Servier and received compensation, and he has received research support from Servier., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n = 57; mean age = 45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3(rd) edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n = 22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition.

We report a case of Hashimoto encephalopathy initially presented as a drug-resistant depression with predominant apathy and asthenia, successfully treated with cyclophosphamide. We suspected that the psychiatric symptoms were due to a deficit in neurotransmitter synthesis related to immune activation. We hypothesized that the immunomodulatory treatment helped to restore the neurotransmitter synthesis and thus decreased the patient’s depressive symptoms. In this case report we propose an innovative model in which immunity might disturbs neurotransmitters synthesis leading to depressive symptoms. [ABSTRACT FROM AUTHOR]