Dépression (psychiatrie) | EPFL Graph Search

La dépression, également appelée dépression caractérisée, dépression clinique ou dépression majeure, est un trouble psychiatrique caractérisé par des épisodes de baisse d'humeur accompagnée de plusieurs autres symptômes tels qu'une faible estime de soi, des difficultés à se concentrer ou à mémoriser, d’une perte ou prise de poids plus ou moins importante, de troubles du sommeil, ainsi que d'une perte de plaisir ou d'intérêt (anhédonie) dans des activités habituellement ressenties comme agréables par la personne. Cet ensemble de symptômes (syndrome individualisé et anciennement classifié dans le groupe des troubles de l'humeur par le manuel diagnostique de l'association américaine de psychiatrie) figure depuis la sortie du DSM-5 en mai 2013 dans la catégorie appelée « troubles dépressifs ». Le terme de peut cependant être ambigu ; il est en effet parfois utilisé dans le langage courant comme abus de langage pour décrire d'autres troubles de l'humeur ou d'autres types de baisse d'hum

Using medical images acquired during routine clinical care for research purposes: a comprehensive medical informatics approach applied to the study of brain development from birth through 2 years of age as indexed by diffusion MRI

Vincent Alexis Roch

Biologic variability and dramatic changes of brain development in children aged 0 to 2 years make it challenging to accurately detect subtle abnormalities in single Magnetic Resonance Imaging (MRI) scans. Diffusion MRI (dMRI) indices such as Apparent Diffusion Coefficient (ADC) are reliable measures of water content in the brain and thus an excellent surrogate marker for brain development. Developing robust age-specific diffusion biomarkers for quantitative measurement of normative brain evolution would enhance our ability to detect subtle alterations due to tissue injuries or neuropathological disorders. Obtaining significant numbers of normative MRI scans for this age group means redirecting clinical data from hospital databases for research purposes. Therefore, this pilot project demonstrates the feasibility of identifying, retrieving and analyzing pediatric clinical dMRI data to investigate normal brain development from birth to 2 years. Research Patient Data Registry (RPDR) at Massachusetts General Hospital (MGH) was used to collect patient medical information and identify healthy children according to radiology reports. Corresponding MRI data were retrieved from MGH Picture Archiving and Communication System (PACS) using the prototype of Medical Imaging Informatics Bench to Bedside (mi2b2) software. A specific pipeline was created to handle the volume of studies and extract technical scan information used to identify comparable diffusion series; 193 studies were used for analysis. Two markers, whole brain average of ADC and Fractional Anisotropy (FA) values (WBAADC and WBAFA), were computed for each patient, their age-evolution across patients was investigated with different models. WBAADC and WBAFA seem to exhibit biexponential decay and increase respectively and might be gender-specific. These results have clinical implications for potentially determining the health status of an unknown individual, and research utility for continued development of these tools.

2011

The HDAC inhibitor SAHA improves depressive-like behavior of CRTC1-deficient mice: Possible relevance for treatment-resistant depression

Jean-René Cardinaux, Pierre Magistretti

Major depression is a highly complex disabling psychiatric disorder affecting millions of people worldwide. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these medications. A better understanding of the neurobiology of depression and the mechanisms underlying antidepressant response is thus critically needed. We previously reported that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) exhibit a depressive-like phenotype and a blunted antidepressant response to the selective serotonin reuptake inhibitor fluoxetine. In this study, we similarly show that Crtc1(-/-) mice are resistant to the antidepressant effect of chronic desipramine in a behavioral despair paradigm. Supporting the blunted response to this tricyclic antidepressant, we found that desipramine does not significantly increase the expression of Bdnf and Nr4a1-3 in the hippocampus and prefrontal cortex of Crtc1(-/-) mice. Epigenetic regulation of neuroplasticity gene expression has been associated with depression and antidepressant response, and histone deacetylase (HDAC) inhibitors have been shown to have antidepressant-like properties. Here, we show that unlike conventional antidepressants, chronic systemic administration of the HDAC inhibitor SAHA partially rescues the depressive-like behavior of Crtc1(-/-) mice. This behavioral effect is accompanied by an increased expression of Bdnf, but not Nr4a1-3, in the prefrontal cortex of these mice, suggesting that this epigenetic intervention restores the expression of a subset of genes by acting downstream of CRTC1. These findings suggest that CRTC1 alterations may be associated with treatment-resistant depression, and support the interesting possibility that targeting HDACs may be a useful therapeutic strategy in antidepressant development. (C) 2016 Elsevier Ltd. All rights reserved.

Elsevier2016

Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression

Jean-René Cardinaux, Pierre Magistretti

Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1(-/-) mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1(-/-) mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1(-/-) prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin-and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1(-/-) mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D-aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1(-/-) mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression.

Nature Publishing Group2016

Vincent Alexis Roch

2011

The HDAC inhibitor SAHA improves depressive-like behavior of CRTC1-deficient mice: Possible relevance for treatment-resistant depression

Jean-René Cardinaux, Pierre Magistretti

Elsevier2016

Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression

Jean-René Cardinaux, Pierre Magistretti

Nature Publishing Group2016