Vascular depression. An age-related mood disorder

Neuropathological and radiological evidences implicating cerebrovascular disease in the pathogenesis of certain types of geriatric depression have led to the relatively recent description of vascular depression, an age-related mood disorder. Its clinical and radiological presentation, the frequent coexistence of cognitive disorders including impairment in executive function and resistance to antidepressant therapy distinguish it from other types of depression. This article presents an overview of the existing literature on the epidemiology, pathophysiology, clinical features and therapeutic particularities of vascular depression. (C) 2010 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.

The 'help' question doesn't help when screening for major depression : external validation of the three-question screening test for primary care patients managed for physical complaints

La dépression majeure est fréquente chez les patients qui consultent un cabinet de médecine générale. Elle reste toutefois difficile à diagnostiquer car elle est souvent masquée par une ou plusieurs plaintes physiques qui sont l'unique motif de consultation. Pour aider le médecin généraliste à démasquer ce trouble, un test de dépistage composé de deux questions a été développé et validé. Ce test indique une probabilité accrue de dépression si le patient répond positivement à au moins une des deux questions suivantes : « Est-ce que, durant le mois qui a précédé, vous vous êtes senti(e) triste, déprimé(e), désespéré(e) ? » et « Durant le mois qui a précédé, avez-vous ressenti un manque d'intérêt et de plaisir dans la plupart des activités que d'habitude vous appréciez ? ». Une troisième question, ajoutée aux deux questions ci-dessus, a été proposée récemment afin d'améliorer les performances de ce test de dépistage. Cette troisième question rend le test négatif si le patient répond négativement à la question suivante : « Souhaitez-vous de l'aide pour cela ? ». Une étude avait indiqué que l'ajout de la question supplémentaire améliorait la spécificité du test sans réduire sa sensibilité. Objectifs Il s'agissait de décrire la performance de deux tests de dépistage de la dépression majeure, composés, respectivement, de deux et de trois questions, dans une population de patients consultant dans un cabinet de médecine générale pour une plainte physique, et de les valider. Méthode Les réponses aux questions des tests de dépistage de la dépression dans la population de la cohorte SODA (Somatisation, Depression, Anxiety) ont été utilisées. Il s'agissait de patients de plus de 18 ans, sélectionnés aléatoirement, consultant pour au moins une plainte physique auprès de 24 médecins généralistes de Suisse Romande, réexaminés une année après l'inclusion dans la cohorte. Le questionnaire validé « Full Patient Health Questionnaire » a été utilisé, le même jour, pour diagnostiquer une dépression majeure. Ce résultat a été utilisé pour évaluer les performances des deux tests de dépistage en calculant la sensibilité et la spécificité, notamment. Résultats Les données de 724 / 937 patients inclus ont pu être utilisées. Un diagnostic de dépression majeure a été posé chez 9.5% des patients (n = 69). La sensibilité et la spécificité des deux questions de dépistage étaient de 91.3% (IC95% : 81.4-96.4%) et 65.0% (IC95% : 61.2-68.6%), respectivement. En ajoutant la troisième question, la sensibilité des deux questions de dépistage a diminué à 59.4% (IC95% : 47.0-70.9%) et la spécificité a augmenté à 88.2% (IC95% : 85.4-90.5%). Conclusions L'utilisation des deux questions pour le dépistage de la dépression majeure est associée à une haute sensibilité et à une basse spécificité chez des patients se présentant en cabinet de médecine générale pour une plainte physique. En ajoutant la troisième question, la spécificité augmente, mais la sensibilité diminue. Ainsi, en ajoutant la troisième question, quatre patients dépressifs majeurs sur dix ne sont pas détectés, alors que seulement un patient sur dix n'est pas détecté avec les deux questions de dépistage. Notre étude montre que le test composé de deux questions reste une méthode de choix pour le dépistage de la dépression majeure et que l'ajout de la troisième question n'est pas recommandée. Celle-ci reste toutefois pertinente dans l'incitation au dialogue sur le sujet de la dépression entre le médecin et son patient.

Variation in the intensity of inbreeding depression among successive life-cycle stages and generations in gynodioecious Silene vulgaris (Caryophyllaceae).

Inbreeding depression is one of the hypotheses explaining the maintenance of females within gynodioecious plant populations. However, the measurement of fitness components in selfed and outcrossed progeny depends on life-cycle stage and the history of inbreeding. Comparative data indicate that strong inbreeding depression is more likely to occur at later life-cycle stages. We used hermaphrodite individuals of Silene vulgaris originating from three populations located in different valleys in the Swiss Alps to investigate the effect of two generations of self- and cross-fertilization on fitness components among successive stages of the life cycle in a glasshouse experiment. We detected significant inbreeding depression for most life-cycle stages including: the number of viable and aborted seeds per fruit, probability of germination, above ground biomass, probability of flowering, number of flowers per plant, flower size and pollen viability. Overall, the intensity of inbreeding depression increased among successive stages of the life cycle and cumulative inbreeding depression was significantly stronger in the first generation (delta approximately 0.5) compared with the second generation (delta approximately 0.35). We found no evidence for synergistic epistasis in our experiment. Our finding of more intense inbreeding depression during later stages of the life cycle may help to explain the maintenance of females in gynodioecious populations of S. vulgaris because purging of genetic load is less likely to occur.

Neuropathological substrates and structural changes in late-life depression: the impact of vascular burden.

A first episode of depression after 65 years of age has long been associated with both severe macrovascular and small microvascular pathology. Among the three more frequent forms of depression in old age, post-stroke depression has been associated with an abrupt damage of cortical circuits involved in monoamine production and mood regulation. Late-onset depression (LOD) in the absence of stroke has been related to lacunes and white matter lesions that invade both the neocortex and subcortical nuclei. Recurrent late-life depression is thought to induce neuronal loss in the hippocampal formation and white matter lesions that affect limbic pathways. Despite an impressive number of magnetic resonance imaging (MRI) studies in this field, the presence of a causal relationship between structural changes in the human brain and LOD is still controversial. The present article provides a critical overview of the contribution of neuropathology in post-stroke, late-onset, and late-life recurrent depression. Recent autopsy findings challenge the role of stroke location in the occurrence of post-stroke depression by pointing to the deleterious effect of subcortical lacunes. Despite the lines of evidences supporting the association between MRI-assessed white matter changes and mood dysregulation, lacunes, periventricular and deep white matter demyelination are all unrelated to the occurrence of LOD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of aging-related neurodegenerative changes in the human brain. However, they also provide data in favor of the neurotoxic theory of depression by showing that neuronal loss occurs in the hippocampus of chronically depressed patients. These three paradigms are discussed in the light of the complex relationships between psychosocial determinants and biological vulnerability in affective disorders.

Significant correction of disease after postnatal administration of recombinant ectodysplasin A in canine X-linked ectodermal dysplasia.

Patients with defective ectodysplasin A (EDA) are affected by X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition characterized by sparse hair, inability to sweat, decreased lacrimation, frequent pulmonary infections, and missing and malformed teeth. The canine model of XLHED was used to study the developmental impact of EDA on secondary dentition, since dogs have an entirely brachyodont, diphyodont dentition similar to that in humans, as opposed to mice, which have only permanent teeth (monophyodont dentition), some of which are very different (aradicular hypsodont) than brachyodont human teeth. Also, clinical signs in humans and dogs with XLHED are virtually identical, whereas several are missing in the murine equivalent. In our model, the genetically missing EDA was compensated for by postnatal intravenous administration of soluble recombinant EDA. Untreated XLHED dogs have an incomplete set of conically shaped teeth similar to those seen in human patients with XLHED. After treatment with EDA, significant normalization of adult teeth was achieved in four of five XLHED dogs. Moreover, treatment restored normal lacrimation and resistance to eye and airway infections and improved sweating ability. These results not only provide proof of concept for a potential treatment of this orphan disease but also demonstrate an essential role of EDA in the development of secondary dentition.

Maintenance of hepatic nuclear factor 6 in postnatal islets impairs terminal differentiation and function of beta-cells.

The Onecut homeodomain transcription factor hepatic nuclear factor 6 (Hnf6) is necessary for proper development of islet beta-cells. Hnf6 is initially expressed throughout the pancreatic epithelium but is downregulated in endocrine cells at late gestation and is not expressed in postnatal islets. Transgenic mice in which Hnf6 expression is maintained in postnatal islets (pdx1(PB)Hnf6) show overt diabetes and impaired glucose-stimulated insulin secretion (GSIS) at weaning. We now define the mechanism whereby maintenance of Hnf6 expression postnatally leads to beta-cell dysfunction. We provide evidence that continued expression of Hnf6 impairs GSIS by altering insulin granule biosynthesis, resulting in a reduced response to secretagogues. Sustained expression of Hnf6 also results in downregulation of the beta-cell-specific transcription factor MafA and a decrease in total pancreatic insulin. These results suggest that downregulation of Hnf6 expression in beta-cells during development is essential to achieve a mature, glucose-responsive beta-cell.

Abnormal sensitivity to negative feedback in late-life depression.

AIMS: The purpose of the present study was to probe sensitivity to potentially misleading negative feedback on cognitive tasks as a possible mechanism of cognitive impairment in elderly patients with mild depression. METHODS: A total of 22 mildly depressed elderly subjects were compared to 22 healthy controls, using a computerized Tower-of-London task. RESULTS: Failure and magnitude of failure were significantly worse after negative but not positive feedback. Depression predicted failure after negative feedback but not the magnitude of failure. Neither failure nor magnitude of failure increased as a consequence of repeated negative feedback. CONCLUSIONS: Altered sensitivity to negative feedback occurs in mild late-life unipolar depression and may represent a subtle context-specific phenomenon.

Periprocedural Hemodynamic Depression Is Associated With a Higher Number of New Ischemic Brain Lesions After Stenting in the International Carotid Stenting Study-MRI Substudy.

BACKGROUND AND PURPOSE: Carotid artery stenting (CAS) is associated with a higher risk of both hemodynamic depression and new ischemic brain lesions on diffusion-weighted imaging than carotid endarterectomy (CEA). We assessed whether the occurrence of hemodynamic depression is associated with these lesions in patients with symptomatic carotid stenosis treated by CAS or CEA in the randomized International Carotid Stenting Study (ICSS)-MRI substudy. METHODS: The number and total volume of new ischemic lesions on diffusion-weighted imaging 1 to 3 days after CAS or CEA was measured in the ICSS-MRI substudy. Hemodynamic depression was defined as periprocedural bradycardia, asystole, or hypotension requiring treatment. The number of new ischemic lesions was the primary outcome measure. We calculated risk ratios and 95% confidence intervals per treatment with Poisson regression comparing the number of lesions in patients with or without hemodynamic depression. RESULTS: A total of 229 patients were included (122 allocated CAS; 107 CEA). After CAS, patients with hemodynamic depression had a mean of 13 new diffusion-weighted imaging lesions, compared with a mean of 4 in those without hemodynamic depression (risk ratio, 3.36; 95% confidence interval, 1.73-6.50). The number of lesions after CEA was too small for reliable analysis. Lesion volumes did not differ between patients with or without hemodynamic depression. CONCLUSIONS: In patients treated by CAS, periprocedural hemodynamic depression is associated with an excess of new ischemic lesions on diffusion-weighted imaging. The findings support the hypothesis that hypoperfusion increases the susceptibility of the brain to embolism. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25337470.

Cell Adhesion Peptide RGDSP and Laminin Support Proliferation and Migration of Postnatal Retinal Stem Cells in a 3D Hydrogel Culture System

Purpose: Retinal stem cells (RSCs) can be isolated from radial glia population of the newborn mouse retina (Angénieux et al., 2006). These RSCs have great capacity to renew and generate neurons including cells differentiated towards the photoreceptor lineage (Mehri-Soussi et al., 2006). However, our published results showed poor integration and survival rate after cell grafting into the retina. The uncontrollable environment of retina seems to be the problem. To bypass this, we are trying to generate hemi-retinal tissue in vitro that can be used for transplantation. Methods: Expanded RSCs were seeded in a mixture of poly-ethylene-glycol (PEG)-polymer-based hydrogels crosslinked by peptides that also serve as substrates for matrix metalloproteinases. Different doses of crosslinker peptides were tested. Several growth factors were studied to stimulate cell proliferation and differentiation. Results: Cells were trapped in hydrogels and cultured in the presence of FGF2 and EGF. Spherical cell clusters indicating proliferation appeared within several days, but there was no cell migration within the gel. We then added cell adhesion molecules integrin ligand RGDSP, or laminin, or a combination of both, into the gel. Cells grown with laminin showed the best proliferation. Cells grown with RGDSP proliferated a few times and then started to spread out. Cells grown with the combination of RGDSP and laminin showed better proliferation than with RGDSP alone and larger spread-outs than with laminin alone. After stimulations with first FGF2 and EGF, and then only FGF2, some cells showed neuronal morphology after 2 weeks. The neuronal population was assessed by the presence of neuronal marker b-tubulin-III. Glial cells were also present. Further characterizations are undergoing. Conclusions: RSC can grow and migrate in 3D hydrogel with the addition of FGF2, EGF, RGDSP and laminin. Further developments are necessary to form a homogenous tissue containing retinal cells.

Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2.

Glut-2 is a low-affinity transporter present in the plasma membrane of pancreatic beta-cells, hepatocytes and intestine and kidney absorptive epithelial cells of mice. In beta-cells, Glut-2 has been proposed to be active in the control of glucose-stimulated insulin secretion (GSIS; ref. 2), and its expression is strongly reduced in glucose-unresponsive islets from different animal models of diabetes. However, recent investigations have yielded conflicting data on the possible role of Glut-2 in GSIS. Whereas some reports have supported a specific role for Glut-2 (refs 5,6), others have suggested that GSIS could proceed normally even in the presence of low or almost undetectable levels of this transporter. Here we show that homozygous, but not heterozygous, mice deficient in Glut-2 are hyperglycaemic and relatively hypo-insulinaemic and have elevated plasma levels of glucagon, free fatty acids and beta-hydroxybutyrate. In vivo, their glucose tolerance is abnormal. In vitro, beta-cells display loss of control of insulin gene expression by glucose and impaired GSIS with a loss of first phase but preserved second phase of secretion, while the secretory response to non-glucidic nutrients or to D-glyceraldehyde is normal. This is accompanied by alterations in the postnatal development of pancreatic islets, evidenced by an inversion of the alpha- to beta-cell ratio. Glut-2 is thus required to maintain normal glucose homeostasis and normal function and development of the endocrine pancreas. Its absence leads to symptoms characteristic of non-insulin-dependent diabetes mellitus.

Assessing depression outcome in patients with moderate dementia: sensitivity of the HoNOS65+ scale.

To date, there is no widely accepted clinical scale to monitor the evolution of depressive symptoms in demented patients. We assessed the sensitivity to treatment of a validated French version of the Health of the Nation Outcome Scale (HoNOS) 65+ compared to five routinely used scales. Thirty elderly inpatients with ICD-10 diagnosis of dementia and depression were evaluated at admission and discharge using paired t-test. Using the Brief Psychiatric Rating Scale (BPRS) "depressive mood" item as gold standard, a receiver operating characteristic curve (ROC) analysis assessed the validity of HoNOS65+F "depressive symptoms" item score changes. Unlike Geriatric Depression Scale, Mini Mental State Examination and Activities of Daily Living scores, BPRS scores decreased and Global Assessment Functioning Scale score increased significantly from admission to discharge. Amongst HoNOS65+F items, "behavioural disturbance", "depressive symptoms", "activities of daily life" and "drug management" items showed highly significant changes between the first and last day of hospitalization. The ROC analysis revealed that changes in the HoNOS65+F "depressive symptoms" item correctly classified 93% of the cases with good sensitivity (0.95) and specificity (0.88) values. These data suggest that the HoNOS65+F "depressive symptoms" item may provide a valid assessment of the evolution of depressive symptoms in demented patients.

Validation of the post-delivery perceived stress inventory

This article presents the post-delivery perceived stress inventory (PDPSI) and its psychometric properties. This inventory is unique in that it links the measurement of perceived stress to events experienced during and after delivery. A total of 235 French-speaking, primiparous mothers completed the PDPSI two days after their delivery. To evaluate the predictive validity of the PDPSI on anxiety and depression, participants also completed the EPDS and the STAI two days and six weeks postpartum. The exploratory analysis revealed a 16-item structure divided into five factors: F1: relationship with the child; F2: delivery; F3: fatigue after delivery; F4: breastfeeding; and F5: relationship with the caregivers. The PDPSI demonstrated good internal consistency. Moreover, confirmatory factor analysis produced excellent indices, indicating that the complexity of the PDPSI was taken into account and its fit to the sample. The discriminant analysis showed that the PDPSI was not sensitive to specific changes in the sample making the inventory generalizable to other populations. Predictive validity showed that the scale significantly predicted depression and anxiety in the early postpartum period as well as anxiety six weeks postpartum. Overall, the PDPSI showed excellent psychometric qualities, making it a useful tool for future research-evaluating interventions related to perceived stress during the postpartum period.

Guidelines for the management of depression and anxiety disorders in primary care.

High risk groups for depression and anxiety disorders include those with co-occuring alcohol or other drug misuse.This resource was contributed by The National Documentation Centre on Drug Use.