Cellular Composition and Contribution of Tertiary Lymphoid Structures to Tumor Immune Infiltration and Modulation by Radiation Therapy

Immune-based anti-cancer strategies combined with radiation therapy (RT) are actively being investigated but many questions remain, such as the ideal treatment scheme and whether a potent immune response can be generated both locally and systemically. In this context, tumor-associated tertiary lymphoid structures (TLS) have become a subject of research. While TLS are present in several types of cancer with strong similarities, they are especially relevant in medullary breast carcinoma (MBC). This suggests that MBC patients are ideally suited for investigating this question and may benefit from adapted therapeutic options. As RT is a corner-stone of MBC treatment, investigating interactions between RT and TLS composition is also clinically relevant. We thus first characterized the lymphoid structures associated with MBC in a patient case report and demonstrated that they closely resemble the TLS observed in a genetical mouse model. In this model, we quantitatively and qualitatively investigated the cellular composition of the tumor-associated TLS. Finally, we investigated TLS regulation after hypo-fractionated RT and showed that RT induced their acute and transient depletion, followed by a restoration phase. This study is the first work to bring a comprehensive and timely characterization of tumor-associated TLS in basal conditions and after RT. It highlights cellular targets (i.e., Tregs) that could be selectively modulated in subsequent studies to optimize anti-tumor immune response. The study of TLS modulation is worth further investigation in the context of RT and personalized medicine

Hypovitaminosis D is associated with depression and anxiety in schizophrenia: results from the national FACE-SZ cohort. Running title: hypovitaminosis D, depression and anxiety in schizophrenia

International audienceBackground. Guidelines have been edited for the treatment of schizophrenia (SZ) and bipola

Structural and functional neural basis of cognitive impairment and quality of life in schizophrenia : a multimodal neuroimaging study

L’objectif principal de ce travail est de caractériser par une approche multimodale d’imagerie les bases neurales structurales et fonctionnelles qui sous-tendent les troubles cognitifs et la QV dans la schizophrénie. L’objectif secondaire est de tester la valeur prédictive des troubles cognitifs et de la QV pour l’évolution et le fonctionnement dans la schizophrénie.Nous avons d’abord exploré les profils d’activation cérébrale au cours d’une tâche de mémoire de travail entre des patients qui ont une courte durée d’évolution de la maladie et ceux qui ont une longue durée d’évolution de la maladie. Nous avons retrouvé une hyper activation de certaines régions cérébrales chez les patients avec un longue durée d’évolution de la maladie comparativement aux patients avec une courte durée d’évolution. Nous avons ensuite étudié les bases neurales structurales de la QV. Nous avons mis en évidence qu’une QV altérée était associée à des changements plus importants de la microstructure cérébrale dans des régions altérées par le processus pathologique de la schizophrénie. Nous avons enfin étudié les réseaux cérébraux fonctionnels qui sous-tendent la QV. Nous rapportons que des régions cérébrales impliquées dans la prise de décision, dans le traitement des émotions et dans les cognitions sociales sont liées aux dimensions de la QV.D’une part nos travaux suggèrent qu’une réorganisation fonctionnelle dans le réseau cérébral de la mémoire de travail joue un rôle compensateur lors de l’évolution de la schizophrénie. D’autre part, nos résultats laissent supposer que la QV serait l’expression précoce des anomalies cérébrales induites par les processus pathologiques de la schizophrénie.We conducted a multimodal neuroimaging approach combining the study of working memory activation with fMRI, the study of microstructural abnormalities associated with impaired QoL using MTI and the study of the functional brain substrate of QoL using SPECT. We aimed to characterize structural and functional neural basis of cognitive impairment and QoL in schizophrenia. We secondarily aimed to test the predictive value of cognitive impairment and QOL for the evolution and functioning in schizophrenia.First, we explored brain activation during a working memory task between patients with short disease duration and patients with long disease duration. We found a functional reorganization in patients with long schizophrenia duration having brain hyperactivations relative to short schizophrenia duration patients. Secondly, we investigated and compared microstructural abnormalities in patients with preserved Qol and impaired QoL. We showed that patients with impaired QoL had more microstructural changes in brain regions affected by the disease process of schizophrenia.Finally, we studied the neural substrate of QoL in schizophrenia. We reported that brain regions involved in cognitions, emotional information processing and social cognition underlie the different QoL dimensions in schizophrenia. On the one hand, our findings suggest that a functional reorganization in the working memory neural network plays a compensatory role in the schizophrenia course. On the other hand, our results suggest that QoL could be the early expression of brain abnormalities induced by the disease process of schizophrenia

L' apport de la neuroimagerie dans la schizophrénie

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Perceptually or conceptually driven recognition: On the specificities of the memory deficit in schizophrenia

International audienceThis study explored the effects of exemplar changes on visual object recognition in patients with schizophrenia and paired control subjects. The experimental design was derived from the process-dissociation procedure (PDP: Jacoby, 1991). The objects presented at test could be the same exemplar as at study (physically identical picture), a different exemplar of the same object category, or a new, non-studied object. In the inclusion task, participants had to generalize their recognition to the conceptual level by accepting both different and identical exemplars as old. In the exclusion task, on the other hand, they had to accept only the same exemplars of the studied objects as old. Overall, performance was better on the inclusion task than on the exclusion task; schizophrenia patients performed worse than controls on the inclusion task but not the exclusion task, misrecognizing different exemplars more often than healthy controls. The present findings reveal that both recollection and familiarity are impaired in patients with schizophrenia, who present a relational, conceptually driven memory deficit. This deficit does not allow them to recognize an object as a member of a specific category independently of perceptual variations. This retrieval mode influences their subjective awareness of items' familiarity, and should be considered as a target for remediation. (C) 2014 Elsevier Ireland Ltd. All rights reserved

Prosodic and lexical entrainment in adults with and without schizophrenia

International audienceEntrainment refers to the tendency people have to speak more similarly during a conversation. Although entrainment has been observed frequently, the underlying mechanisms of the phenomenon are debated. A specific point of disagreement is the role of social or higher-order cognitive factors in entrainment. The present study aimed to explore prosodic and lexical entrainment in small groups of individuals with schizophrenia, a disorder that has been associated with theory of mind impairments and social difficulties, and a control group without schizophrenia. All participants completed a referential communication task with an experimenter. To determine prosodic entrainment, the measures proposed by Levitan and Hirshberg [1] were used. Results seem to suggest that the effect of task role on prosodic entrainment was larger than any possible effects of group, suggesting that social factors affect prosodic entrainment behaviour more than individual differences in cognition or other factors. Conversely, lexical entrainment was not affected by task role or group. Importantly, no clear patterns in entrainment on different dimensions, levels, or features could be observed, highlighting the complex and multifaceted nature of entrainment

Est-ce que des patients atteints de schizophrénie s'adaptent à leur interlocuteur durant une conversation?

International audienceAlors que de nombreuses recherches ont clairement mis en évidence des troubles de la théorie de l’esprit (ToM) dans la schizophrénie (Brüne, 2005) très peu d’études ont évalué ces difficultés en situation d’interaction (McCabe et al., 2004 ; Champagne-Lavau et al., 2009 ; Michelas et al., 2014). Pourtant, si l’attribution d’états mentaux aux autres (ToM) est le plus souvent implicite, rapide et spontanée dans nos interactions quotidiennes, les tâches classiques utilisées pour évaluer cette capacité dans la schizophrénie mettent surtout en jeu des processus lents et coûteux cognitivement.L’objectif de la présente étude était de mieux caractériser les capacités des patients atteints de schizophrénie à attribuer des connaissances et croyances à autrui en les impliquant dans une situation de conversation

Functional brain substrate of quality of life in patients with ă schizophrenia: A brain SPECT multidimensional analysis

International audienceThe aim of this study was to investigate the functional brain substrate ă of quality of life (QoL) in patients with schizophrenia. Participants ă comprised 130 right-handed patients with schizophrenia who underwent ă whole-brain single photon emission computed tomography (SPECT) with ă Tc-99m-labeled ethylcysteinate dimer (Tc-99m-ECD) for exploring ă correlations of regional cerebral blood flow (rCBF) with the eight ă dimensions score of the Schizophrenia Quality of Life questionnaire ă (S-QoL 18). A significant positive correlation was found between the ă global index of the S-QoL 18 and rCBF in the right superior temporal ă sulcus and between psychological well-being dimension and rCBF in ă Brodmann area (BA)6, BA8, BA9, and BA10 and between self-esteem ă dimension and rCBF in striatum and between family relationship dimension ă and rCBF in BA1, BA2, BA3, BA4, BA8, BA22, BA40, BA42 and BA44 and ă between relationship with friends dimension and rCBF in BA44 and between ă physical well-being dimension and rCBF in parahippocampal gyrus, and ă finally between autonomy dimension and rCBF in cuneus and precuneus. A ă significant negative correlation was found between resilience dimension ă and rCBF in precuneus and between sentimental life dimension and rCBF in ă BA10. Our findings provide neural correlates of QoL. Brain regions ă involved in cognitions, emotional information processing and social ă cognition underlie the different QoL dimensions. (C) 2016 Published by ă Elsevier Ireland Ltd

Attribution of mental states during conversation in schizophrenia: Features of poor mentalisers

International audienceA deficit in social cognition including theory of mind (ToM) is one of the most disabling clinical characteristics of schizophrenia. Very few studies have investigated these impairments in schizophrenia during natural communication situations (McCabe et al. 2004, Champagne-Lavau et al. 2009). Recent findings have shown that people with schizophrenia (SZ) may be more or less impaired in their ToM skills (Pickup and Frith, 2001; Champagne-Lavau et al., 2009; Brüne and Schaub, 2012). Indeed, 50% to 80% of SZ patients may show difficulties to attribute mental states (Brüne & Schaub, 2012). Using a classical ToM task (i.e. MSAT), Brüne & Schaub (2012) showed that, by comparison to SZ patients with fair ToM abilities, SZ patients with poor ToM abilities were characterized by social behavioral abnormalities, disorganization and excitement symptoms, with absence of executive dysfunction. However, observing a social interaction is not equivalent to participating in a social interaction in terms of the cognitive processes involved in the attribution of mental states to other. Thus, the aim of the present study was to examine characteristics of relatively impaired SZ patients (SZ-I) and relatively unimpaired SZ patients (SZ-U) on a ToM task assessing attribution of knowledge during a situation of conversation

Toward a transdiagnostic tool to evaluate depressive symptoms across mental disorders: Validation of the Calgary depression rating scale in patients with major depressive disorder

International audienc