Neuropsychological predictors of treatment outcome in obsessive compulsive disorder (OCD)

Contexte: En dépit de la preuve substantielle pour l'efficacité générale de la thérapie cognitivo-comportementale pour le trouble obsessionnel-compulsif (TOC), il existe une controverse à propos de l'amélioration de certains déficits neuropsychologiques dans ce trouble. Objectif: Le but de cette étude est d'évaluer: 1) la corrélation de la gravité du TOC et les résultats des tests neuropsychologiques et 2) l'amélioration clinique et neuropsychologique des patients souffrant de TOC qui ont terminé avec succès leur traitement. Méthode: Cette étude évalue les fonctions neurocognitives et l'état clinique de 27 participants du groupe TOC et 25 participants du groupe témoin. La fonction neurocognitive de chaque participant a été évaluée en utilisant le test de Rey-Osterreich Figure complexe (RCFT), le test de fluidité D-KEFS et l’essai Cardebat-D. Nous avons également, utilisé l'inventaire d'anxiété de Beck (IAB), l’Inventaire de dépression de Beck (IDB) et l'échelle d'obsession-compulsion de Yale-Brown (Y-BOCS) pour vérifier la présence de l'anxiété et de la dépression avec le TOC et la gravité des symptômes chez les patients souffrant de TOC. Résultats: Notre étude conclut qu’il y une différence significative de la fonction de la mémoire selon le score au sous test de copie entre les participants souffrant de TOC et le groupe témoin. De plus, nous avons constaté une différence considérable dans le score de rappel immédiat et différé du RCFT avant et après le traitement dans le groupe de TOC. Conclusion: En résumé, la présente étude a démontré que les patients atteints de TOC ont des troubles cognitifs spécifiques et que la thérapie cognitivo-comportementale serait un traitement qui pourrait améliorer, au moins, certaines dysfonctions neurocognitives.

Identification and characterization of new biomarkers in aggressive subtypes of breast cancer

En 2015, la récidive tumorale et les métastases du cancer du sein demeurent une cause importante de décès à travers le monde. Toutefois, ces cancers sont souvent hétérogènes car en dépit d’un phénotype similaire, l’évolution clinique et la réponse au traitement peuvent varier considérablement. Il y a donc un intérêt évident à identifier et à caractériser de nouveaux biomarqueurs pour permettre classer les tumeurs mammaires dans des sous-groupes plus homogènes. Notre hypothèse est que chaque cancer mammaire possède des caractéristiques distinctes au plan des altérations du génome et des profils d’expression géniques et que ces changements se traduisent cliniquement par une prédisposition à former des métastases ou à répondre ou non à la chimiothérapie et aux thérapies ciblées. Dans le cadre de nos travaux, nous nous sommes intéressés aux sous-types agressifs de tumeurs mammaires et notamment les cancers de type triple négatif. Nous avons aussi tenté d’identifier des marqueurs capables de distinguer l’une de l’autre les tumeurs de type luminal A et luminal B. Pour ce faire, nous avons d’abord utilisé une stratégie in silico à partir de données publiques (micro-puces d’ADN et séquençage de l’ARN). Nous avons ensuite construit sept micro-matrices tissulaires (TMA) provenant de tissus mammaires normaux et tumoraux fixés à la formaline et enrobés en paraffine. Ces outils nous ont permis d’évaluer par immunohistochimie les niveaux d’expression différentielle des marqueurs suivants : ANXA1, MMP-9, DP103 et MCM2. Ceux-ci ont été comparés aux marqueurs usuels du cancer du sein (ER, PR, HER2, CK5/6 et FOXA1) et corrélés aux données cliniques (survie globale et métastase). Nos résultats indiquent que ces nouveaux marqueurs jouent un rôle important dans l’évolution clinique défavorable des tumeurs de haut grade. Dans un premier article nous avons montré que l’expression d’ANXA1 est dérégulée dans les cancers de type triple-négatif et aussi, dans une certaine mesure, dans les tumeurs HER2+. Nous croyons qu’ANXA1 permet de mieux comprendre le processus d’hétérogénéité tumorale et facilite l’identification des tumeurs de haut grade. Nous proposons également qu’ d’ANXA1 stimule la transition épithélio-mésenchymateuse (EMT) et la formation des métastases. Dans un second temps, nous avons montré que les niveaux d’expression de MMP-9 reflètent la différenciation cellulaire et corrèlent avec les sous-types de cancers mammaires ayant un mauvais pronostic. Nous estimons que MMP-9 permet de mieux comprendre et d’identifier les tumeurs mammaires à haut risque. De fait, la surexpression de MMP-9 est associée à une augmentation des métastases, une récidive précoce et une diminution de la survie globale. Dans le cadre d’un troisième article, nous avons montré que la surexpression du marqueur de prolifération MCM2 s’observe dans les cancers triple-négatifs, HER2+ et Luminal B par comparaison aux cancers luminal A (p< 0.0001). Nos résultats suggèrent qu’en utilisant un seuil de 40% de noyaux marqués, nous pourrions distinguer l’une de l’autre les tumeurs de type luminal A et luminal B. Cela dit, avant de pouvoir envisager l’utilisation de ce marqueur en clinique, une étude de validation sur une nouvelle cohorte de patientes s’impose. En somme, les résultats de nos travaux suggèrent qu’ANXA1, MMP-9 et MCM2 sont des marqueurs intéressants pour mieux comprendre les mécanismes physiopathologiques impliqués dans la progression tumorale et le développement des métastases. À terme, ces nouveaux marqueurs pourraient être utilisés seuls ou en combinaison avec d’autres gènes candidats pour permettre le développement de trousses « multigènes » ou d’essais protéomiques multiplex pour prédire l’évolution clinique des cancers mammaires.

Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor Subtypes Gene Expression in Insulin Induced Hypoglycemic Rat Brain Regions: Functional Regulation through Phospholipase C and CREB Protein

In the present study, a detailed investigation on the alterations of muscarinic M1, M3, α7 nicotinic acetylcholine receptor (α7 nAchR), GABA receptors and its subtypes; GABAAα1 and GABAB in the brain regions of streptozotocin induced diabetic and insulin induced hypoglycemic rats were carried out. Gene expression of acetylcholine esterase (AChE), choline acetyltransferase (ChAT), GAD, GLUT3, Insulin receptor, superoxide dismutase (SOD), Bax protein, Phospholipase C and CREB in hypoglycemic and hyperglycemic rat brain were studied. Muscarinic M1, M3 receptors, AChE, ChAT, GABAAα1, GABAB, GAD, Insulin receptor, SOD, Bax protein and Phospholipase C expression in pancreas was also carried out. The molecular studies on the CNS and PNS damage will elucidate the therapeutic role in the corrective measures of the damage to the brain during hypoglycemia and hyperglycemia.

Dopamine Receptor Subtypes,IP3, cAMP and cGMP Functional Regulation in Parkinsonism Induced by Unilateral Infusion of Rotenone in Rats: Recovery with Bone Marrow Cells,Serotonin and GABA Supplementation

In the present study, the effects of 5-HT, GABA and Bone Marrow Cells infused intranigrally to substantia nigra individually and in combinations on unilateral rotenone infused Parkinsonism induced rats. Scatchard analysis of DA, DA D1 and D2 receptors in the corpus striatum, cerebral cortex, cerebellum, brain stem and hippocampus showed a significant increase in the Brain regions of rotenone infused rat compared to control. Real Time PCR amplification of DA D1, D2, Bax and ubiquitin carboxy-terminal hydrolase were up regulated in the brain regions of rotenone infused rats compared to control. Gene expression studies of -Synuclien, cGMP and Cyclic AMP response element-binding protein showed a significant down regulation in Rotenone infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies.Our study demonstrated that BMC administration alone cannot reverse the above said molecular changes occurring in PD rat. 5-HT and GABA acting through their specific receptors in combination with bone marrow cells play a crucial role in the functional recovery of PD rats. 5-HT, GABA and Bone marrow cells treated PD rats showed significant reversal to control in DA receptor binding and gene expression. 5-HT and GABA have co-mitogenic property. Proliferation and differentiation of cells re-establishing the connections in Parkinson's disease facilitates the functional recovery. Thus, it is evident that 5-HT and GABA along with BMC to rotenone infused rats renders protection against oxidative, related motor and cognitive deficits which makes them clinically significant for cellbased therapy. The BMC transformed to neurons when co-transplanted with 5-HT and GABA which was confirmed with PKH2GL and nestin. These newly formed neurons have functional significance in the therapeutic recovery of Parkinson’s disease.

Cholinergic receptor subtypes functional regulation in spinal cord injured monoplegic rats

The present study deals with the Cholinergic Receptor subtypes functional regulation in spinal cord injured monoplegic rats: Effect of 5-HT GABA and bone marrow cells.Spinal cord injury causes permanent and irrevocable motor deficits and neurodegeneration. Disruption of the spinal cord leads to diminished transmission of descending control from the brain to motor neurons and ascending sensory information. Behavioural studies showed deficits in motor control and coordination in SCI rats. Cholinergic system plays an important role in SCI, the evaluation of which provides valuable insight on the underlying mechanisms of motor deficit that occur during SCI. The cholinergic transmission was studied by assessing the muscarinic and nicotinic receptors; cholinergic enzymes- ChAT and AChE; second messenger enzyme PLC; transcription factor CREB and second messengers - IP3, cAMP and cGMP. We observed a decrease in the cholinergic transmission in the brain and spinal cord of SCI rats. The disrupted cholinergic system is the indicative of motor deficit and neuronal degeneration in the spinal cord and brain regions. SCI mediated oxidative stress and apoptosis leads to neuronal degeneration in SCI rats. The decreased expression of anti oxidant enzymes – SOD, GPx and neuronal cell survival factors - BDNF, GDNF, IGF-1, Akt and cyclin D2 along with increased expression of apoptotic factors – Bax, caspase-8, TNFa and NF-kB augmented the neuronal degeneration in SCI condition. BMC administration in combination with 5-HT and GABA in SCI rats showed a reversal in the impaired cholinergic neurotransmission and reduced the oxidative stress and apoptosis. It also enhanced the expression of cell survival factors in the spinal cord region. In SCI rats treated with 5-HT and GABA, the transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the spinal cord. Neurotrophic factors and anti-apoptotic elements in SCI rats treated with 5-HT and GABA along with BMC rendered neuroprotective effects accompanied by improvement in behavioural deficits. This resulted in a significant reversal of altered cholinergic neurotransmission in SCI. The restorative and neuro protective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of SCI.

Serotonin receptor subtypes functional regulation and oxidative stress mediated apoptosis in 6-hydroxydopamine lesioned Parkinsonian rats

Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the SNpc resulting in severe motor impairments. Serotonergic system plays an important regulatory role in the pathophysiology of PD in rats, the evaluation of which provides valuable insight on the underlying mechanisms of motor, cognitive and memory deficits in PD. We observed a decrease in 5-HT content in the brain regions of 6-OHDA infused rat compared to control. The decreased 5-HT content resulted in a decrease of total 5-HT, 5-HT2A receptors and 5-HTT function and an increase of 5-HT2C receptor function. 5-HT receptor subtypes - 5-HT2A and 5-HT2C receptors have differential regulatory role on the modulation of DA neurotransmission in different brain regions during PD. Our observation of impaired serotonergic neurotransmission in SNpc, corpus striatum, cerebral cortex, hippocampus, cerebellum and brain stem demonstrate that although PD primarily results from neurodegeneration in the SNpc, the associated neurochemical changes in other areas of the brain significantly contributes to the different motor and non motor symptoms of PD. The antioxidant enzymes – SOD, CAT and GPx showed significant down regulation which indicates increased oxidative damage resulting in neurodegeneration. We also observed an increase in the level of lipid peroxidation. Reduced expression of anti-apoptotic Akt and enhanced expression of NF-B resulting from oxidative stress caused an activation of caspase-8 thus leading the cells to neurodegeneration by apoptosis. BMC administration in combination with 5-HT and GABA to PD rats showed reversal of the impaired serotonergic neurotransmission and oxidative stress mediated apoptosis. The transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the SNpc along with an increase in DA content and an enhanced expression of TH. Neurotrophic factors – BDNF and GDNF rendered neuroprotective effects accompanied by improvement in behavioural deficits indicating a significant reversal of altered dopaminergic and serotonergic neurotransmission in PD. The restorative and neuroprotective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of PD.

Dopamine receptor subtypes functional regulation in insulin induced hypoglycemic neonatal rats: Effect of Glucose, Bacopa monnieri and Bacoside A resuscitation

In the present work we studied the potential of Bacopa monnieri and Bacoside A treatment to enhance the antioxidant system and support the neuronal survival in the hypoglycemic neonatal brain. For achieving the aim, DAD1 and DAD2 receptors functional regulation, gene expression of growth factors, neuronal survival and apoptotic factors during insulin induced hypoglycemic neonatal brain in rats were studied.

Adrenergic and muscarinic receptor subtypes functional regulation during diabetogenesis: Effect of curcumin and vitamin D3 pre-treatment

In the present study, the initial phase was directed to confirm the effects of curcumin and vitamin D3 in preventing or delaying diabetes onset by studying the blood glucose and insulin levels in the pre-treated and diabetic groups. Behavioural studies were conducted to evaluate the cognitive and motor function in experimental rats. The major focus of the study was to understand the cellular and neuronal mechanisms that ensure the prophylactic capability of curcumin and vitamin D3. To elucidate the mechanisms involved in conferring the antidiabetogenesis effect, we examined the DNA and protein profiles using radioactive incorporation studies for DNA synthesis, DNA methylation and protein synthesis. Furthermore the gene expression studies of Akt-1, Pax, Pdx-1, Neuro D1, insulin like growth factor-1 and NF-κB were done to monitor pancreatic beta cell proliferation and differentiation. The antioxidant and antiapoptotic actions of curcumin and vitamin D3 were examined by studying the expression of antioxidant enzymes - SOD and GPx, and apoptotic mediators like Bax, caspase 3, caspase 8 and TNF-α. In order to understand the signalling pathways involved in curcumin and vitamin D3 action, the second messengers, cAMP, cGMP and IP3 were studied along with the expression of vitamin D receptor in the pancreas. The neuronal regulation of pancreatic beta cell maintenance, proliferation and insulin release was studied by assessing the adrenergic and muscarinic receptor functional regulation in the pancreas, brain stem, hippocampus and hypothalamus. The receptor number and binding affinity of total muscarinic, muscarinic M1, muscarinic M3, total adrenergic, α adrenergic and β adrenergic receptor subtypes were studied in pancreas, brain stem and hippocampus of experimental rats. The mRNA expression of muscarinic and adrenergic receptor subtypes were determined using Real Time PCR. Immunohistochemistry studies using confocal microscope were carried out to confirm receptor density and gene expression results. Cell signalling alterations in the pancreas and brain regions associated with diabetogenesis and antidiabetogenesis were assessed by examining the gene expression profiles of vitamin D receptor, CREB, phospholipase C, insulin receptor and GLUT. This study will establish the anti-diabetogenesis activity of curcumin and vitamin D3 pre-treatment and will attempt to understand the cellular, molecular and neuronal control mechanism in the onset of diabetes.Administration of MLD-STZ to curcumin and vitamin D3 pre-treated rats induced only an incidental prediabetic condition. Curcumin and vitamin D3 pretreated groups injected with MLD-STZ exhibited improved circulating insulin levels and behavioural responses when compared to MLD-STZ induced diabetic group. Activation of beta cell compensatory response induces an increase in pancreatic insulin output and beta cell mass expansion in the pre-treated group. Cell signalling proteins that regulate pancreatic beta cell survival, insulin release, proliferation and differentiation showed a significant increase in curcumin and vitamin D3 pre-treated rats. Marked decline in α2 adrenergic receptor function in pancreas helps to relent sympathetic inhibition of insulin release. Neuronal stimulation of hyperglycemia induced beta cell compensatory response is mediated by escalated signalling through β adrenergic, muscarinic M1 and M3 receptors. Pre-treatment mediated functional regulation of adrenergic and cholinergic receptors, key cell signalling proteins and second messengers improves pancreatic glucose sensing, insulin gene expression, insulin secretion, cell survival and beta cell mass expansion in pancreas. Curcumin and vitamin D3 pre-treatment induced modulation of adrenergic and cholinergic signalling in brain stem, hippocampus and hypothalamus promotes insulin secretion, beta cell compensatory response, insulin sensitivity and energy balance to resist diabetogenesis. Pre-treatment improved second messenger levels and the gene expression of intracellular signalling molecules in brain stem, hippocampus and hypothalamus, to retain a functional neuronal response to hyperglycemia. Curcumin and vitamin D3 protect pancreas and brain regions from oxidative stress by their indigenous antioxidant properties and by their ability to stimulate cellular free radical defence system. The present study demonstrates the role of adrenergic and muscarinic receptor subtypes functional regulation in curcumin and vitamin D3 mediated anti-diabetogenesis. This will have immense clinical significance in developing effective strategies to delay or prevent the onset of diabetes.

Clinical features and treatment response in social phobia : Axis II comorbidity and social phobia subtypes

Resumen tomado de la publicaci??n

Cognitive-behavior therapy for compulsive checking in OCD

There is substantial evidence for the effectiveness of psychological treatments for OCD, and various approaches have been widely recommended. These approaches tend to be characterized by exposure and response prevention (ERP) and also tend to be applied equally to all forms of OCD. Patients/clients (and some therapists) often find ERP to be a difficult treatment, and both dropout and refusal rates are unacceptably high. Based on specific cognitive conceptualizations of different manifestations of OCD, new and refined cognitive treatment methods are now available. The present article describes a specific cognitively based approach to the treatment of compulsive checking.

Separating hoarding from OCD

There is confusion about the status of excessive hoarding. In particular, there is an unresolved question about whether or not it is a manifestation of obsessive-compulsive disorder (OCD). There are some definite similarities between 'compulsive' hoarding and OCD, but they are outweighed by the differences between them. It is proposed that the matter can be clarified by separating hoarding from OCD, and that this would advance clinical work and research. (c) 2009 Elsevier Ltd. All rights reserved.

Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential

The host adaptation of influenza virus is partly dependent on the sialic acid (SA) isoform bound by the viral hemagglutinin (HA). Avian influenza viruses preferentially bind the α-2,3 SA and human influenza viruses the α-2,6 isoform. Each isoform is predominantly associated with different surface epithelial cell types of the human upper airway. Using recombinant HAs and human tracheal airway epithelial cells in vitro and ex vivo, we show that many avian HA subtypes do not adhere to this canonical view of SA specificity. The propensity of avian viruses to adapt to human receptors may thus be more widespread than previously supposed.

Investigating subtypes of reward processing deficits as trait markers for depression

Background: Anhedonia, the loss of pleasure in usually enjoyable activities, is a central feature of major depressive disorder (MDD). The aim of the present study was to examine whether young people at a familial risk of depression display signs of anticipatory, motivational or consummatory anhedonia, which would indicate that these deficits may be trait markers for MDD. Methods: The study was completed by 22 participants with a family history of depression (FH+) and 21 controls (HC). Anticipatory anhedonia was assessed by asking participants to rate their anticipated liking of pleasant and unpleasant foods which they imagined tasting when cued with images of the foods. Motivational anhedonia was measured by requiring participants to perform key presses to obtain pleasant chocolate taste rewards or to avoid unpleasant apple tastes. Additionally, physical consummatory anhedonia was examined by instructing participants to rate the pleasantness of the acquired tastes. Moreover, social consummatory anhedonia was investigated by asking participants to make preference-based choices between neutral facial expressions, genuine smiles, and polite smiles. Results: It was found that the FH+ group’s anticipated liking of unpleasant foods was significantly lower than that of the control group. By contrast, no group differences in the pleasantness ratings of the actually experienced tastes or in the amount of performed key presses were observed. However, controls preferred genuine smiles over neutral expressions more often than they preferred polite smiles over neutral expressions, while this pattern was not seen in the FH+ group. Conclusion: These findings suggest that FH+ individuals demonstrate an altered anticipatory response to negative stimuli and show signs of social consummatory anhedonia, which may be trait markers for depression.