Predictors of mental well-being over the first lockdown period due to the COVID-19 pandemic in France. A repeated cross-sectional study

IntroductionNumerous studies have investigated the positive and negative effects of potential predictors of well-being during lockdowns due to COVID-19. Yet, little is known on whether these effects significantly changed with time spent in lockdown. In the current study, we described the association of mental well-being with a large number of background characteristics (e.g., socio-demographic or health-related factors), COVID-related factors, and coping strategies, over the duration of the first lockdown due to COVID-19 in France.MethodsA nationwide online survey was conducted over 7 of the 8 weeks of the 1st lockdown in France, i.e., from 25 March 2020 to 10 May 2020. The level of mental well-being was reported using the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). We also measured various background characteristics (e.g., age, sex, education, health issues), COVID-related factors (e.g., health and economic risks, agreement with lockdown), and coping strategies. Our analytical strategy enabled us to disentangle effects aggregated over the study period from those that linearly vary with time spent in lockdown.ResultsOur final dataset included 18,957 participants. The level of mental well-being dropped gradually from the third to the eighth week of lockdown [49.7 (sd 7.9) to 45.5 (sd 10.6)]. Time in lockdown was associated with a decrease in well-being (for each additional 10 days of lockdown: B = −0.30, 95%CI: −0.62, −0.15). Factors that showed significantly negative and positive effects on well-being as time in lockdown progressed were (for each additional 10 days of lockdown): having current psychiatric problems (B = −0.37; 95%CI: −0.63, −0.04), worries about having access to personal protective equipment (B = −0.09; 95%CI: −0.18, −0.01), coping by having positive beliefs about the future of the pandemics (B = 0.29; 95%CI: 0.04, 0.62), being supported by neighbors (B = 0.24; 95%CI: 0.04, 0.44), and being involved in collective actions (B = 0.23; 95%CI: 0.04, 0.46).DiscussionParticipants from our sample saw a drop in their mental well-being throughout the first period of COVID-19 lockdown. Policymakers should be mindful of factors contributing to greater deterioration of mental well-being over time, such as having current psychiatric issues. Promoting collective actions and local support from neighbors may alleviate the deterioration of mental well-being over time

mRNA-based approach to monitor recombinant gamma-interferon restoration of LPS-induced endotoxin tolerance

Introduction: It is now well accepted that sepsis is associated with the development of a pronounced immunosuppressive state, characterized by severe immune alterations (e.g. reduced proliferative capacity, endotoxin tolerance, apoptosis) participating in increased mortality and susceptibility to nosocomial infections. Efforts are currently aimed at restoring a functional immune response in septic patients. Successful therapydepends on the identification of appropriate immunostimulatory drugs and on the development of suitable biomarkers that could be used to stratify patients and to follow response to treatment.Methods: In this study, we evaluated the ex vivo effect of recombinant interferon gamma (rIFN-g) in restoring monocyte functionality (endotoxin-induced Tumor Necrosis Factor-a production) in a two-hit model of endotoxin tolerance (ET) with peripheral blood mononuclear cells from healthy volunteers and in whole blood of septic shockpatients. Importantly, we used quantitative-reverse transcription polymerase-chain reaction to monitor the effect of rIFN-g on the expression of seven genes known to participate in ET (TNF-a, IL-10, HLA-DRA, CIITA, IRAK-M, ABIN-3 and LY64).Results: Expression analysis of those genes confirmed the presence of an immunosuppression state and the ex vivo restoration of immune functions by rIFN-g. We show for the first time that rIFN-g is able to bypass, at the mRNA level, the effect of negative regulators of the LPS signalling pathway such as IRAK-M, ABIN-3 and LY64.Conclusions: Overall, mRNA expressions of a panel of genes could represent promising candidates for the ex vivo evaluation of rIFN-g effect on monocyte functionality. This ex vivo translational research study demonstrates the potential of a mRNA-based approach to successfully monitor drug efficacy

Architecture du contrôle cognitif au sein du cortex cérébral dans la schizophrénie

The goal of this thesis is to investigate the functional organization of cognitive control within the LPFC in schizophrenia. We used a model postulating that cognitive control is functionally organized within the lateral prefrontal cortex (LPFC) as a cascade of representations ranging from premotor to anterior LPFC regions according to stimuli, the present perceptual context, and the temporal episode in which stimuli occur. Using functional magnetic resonance imaging, we investigated the functional architecture of cognitive control within the LPFC in 15 schizophrenic patients and 14 matched healthy controls. In a first study, we found that immediate contextual signals insufficiently bias the caudal LPFC activity required to select the appropriate behavioral representation. This specific deficit could thus alter the internal consistency of schizophrenic patients’ behavior. To compensate for this weakening of contextual influence, schizophrenic patients may inefficiently use temporal episodic information through higher activation in rostral LPFC regions. In a second study, we showed that schizophrenic patients inappropriately process episodic information flow along a rostro-caudal axis within the LPFC. This top-down episodic control dysfunction could lead to a disruption of episodic memory that could account for the patients’ difficulties in organizing their behavior across time. All the results argue in favor of both dysfunctional specialization and integration within the LPFC in schizophrenia.Le but de cette thèse est d’investiguer l’organisation fonctionnelle du contrôle cognitif au sein du cortex préfrontal latéral dans la schizophrénie. Chez le sujet sain, Koechlin et coll. (Science, 2003) ont montré que le cortex préfrontal latéral était structuré en une cascade de processus de contrôle allant des régions antérieures aux régions postérieures, intégrant respectivement les informations épisodiques (événements antérieurs) et contextuelles (le contexte immédiat de l’action) au choix de l’action en réponse à un stimulus externe. En utilisant le paradigme expérimental de Koechlin et coll. en IRM fonctionnelle, nous avons investigué l’architecture fonctionnelle du contrôle cognitif au sein du cortex latéral préfrontal chez 15 patients schizophrènes et 14 sujets contrôles appariés. Dans une première étude, nous avons trouvé que les patients schizophrènes présentaient un déficit sélectif du contrôle contextuel associé à une hypoactivation des régions postérieures préfrontales, expliquant la désorganisation du discours et du comportement observés chez ces patients. Par ailleurs, les patients schizophrènes hyperactivaient leurs régions rostrales du cortex préfrontal latéral pendant le contrôle des informations de nature épisodique, ce que nous avons interprété comme une tentative de compensation infructueuse des dysfonctions du contrôle contextuel. Dans une seconde étude, nous avons montré que les patients schizophrènes présentaient également une perturbation du traitement top-down des informations de nature épisodique, liée à une dysconnectivité des régions rostrales vers les régions caudales du cortex préfrontal latéral

Architecture of cognitive control within the cerebral cortex in schizophrenia

Le but de cette thèse est d’investiguer l’organisation fonctionnelle du contrôle cognitif au sein du cortex préfrontal latéral dans la schizophrénie. Chez le sujet sain, Koechlin et coll. (Science, 2003) ont montré que le cortex préfrontal latéral était structuré en une cascade de processus de contrôle allant des régions antérieures aux régions postérieures, intégrant respectivement les informations épisodiques (événements antérieurs) et contextuelles (le contexte immédiat de l’action) au choix de l’action en réponse à un stimulus externe. En utilisant le paradigme expérimental de Koechlin et coll. en IRM fonctionnelle, nous avons investigué l’architecture fonctionnelle du contrôle cognitif au sein du cortex latéral préfrontal chez 15 patients schizophrènes et 14 sujets contrôles appariés. Dans une première étude, nous avons trouvé que les patients schizophrènes présentaient un déficit sélectif du contrôle contextuel associé à une hypoactivation des régions postérieures préfrontales, expliquant la désorganisation du discours et du comportement observés chez ces patients. Par ailleurs, les patients schizophrènes hyperactivaient leurs régions rostrales du cortex préfrontal latéral pendant le contrôle des informations de nature épisodique, ce que nous avons interprété comme une tentative de compensation infructueuse des dysfonctions du contrôle contextuel. Dans une seconde étude, nous avons montré que les patients schizophrènes présentaient également une perturbation du traitement top-down des informations de nature épisodique, liée à une dysconnectivité des régions rostrales vers les régions caudales du cortex préfrontal latéral.The goal of this thesis is to investigate the functional organization of cognitive control within the LPFC in schizophrenia. We used a model postulating that cognitive control is functionally organized within the lateral prefrontal cortex (LPFC) as a cascade of representations ranging from premotor to anterior LPFC regions according to stimuli, the present perceptual context, and the temporal episode in which stimuli occur. Using functional magnetic resonance imaging, we investigated the functional architecture of cognitive control within the LPFC in 15 schizophrenic patients and 14 matched healthy controls. In a first study, we found that immediate contextual signals insufficiently bias the caudal LPFC activity required to select the appropriate behavioral representation. This specific deficit could thus alter the internal consistency of schizophrenic patients’ behavior. To compensate for this weakening of contextual influence, schizophrenic patients may inefficiently use temporal episodic information through higher activation in rostral LPFC regions. In a second study, we showed that schizophrenic patients inappropriately process episodic information flow along a rostro-caudal axis within the LPFC. This top-down episodic control dysfunction could lead to a disruption of episodic memory that could account for the patients’ difficulties in organizing their behavior across time. All the results argue in favor of both dysfunctional specialization and integration within the LPFC in schizophrenia

Approche neuroéconomique de la prise de risque à l'adolescence

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Country-level association of socio-cultural factors with the burden of four common mental disorders. An ecological analysis using the Global Burden of Disease database

Developed countries have been related to a higher prevalence of mental disorders. This led us to hypothesize that cultural values typical of developed countries could be associated with mental disorders. Here, we sought to determine the association of indulgence (seeking momentary pleasure and freely expressing oneself) and individualism (being able to deviate from in-group norms) with the burden of four mental disorders: depressive, bipolar, anxiety, and eating disorders. We controlled for socio-economic factors (socio-demographic development, income inequality, and unemployment rate), negative life experiences, quality of health care systems, and quality of measurements. We also included world regions fixed effects to account for unobserved geo-spatial factors clustered at the regional level. Our sample included ninety-seven countries. Fully adjusted models revealed that indulgence was associated with an increase in the burden of all four disorders (p \u3c 0.05). A 30 points increase in the indulgence dimension (from Italy = 47 to the UK = 77) was associated with an increase in DALYs by 8.4% (depressive disorders) to 21.0% (eating disorders). Other factors did not demonstrate any such systematic association. Developed nations may be exposed to mental disorders due to socio-cultural factors: seeking pleasure and freedom might be deleterious to population-level mental health

Association of globalization with the burden of opioid use disorders 2019. A country-level analysis using targeted maximum likelihood estimation

Abstract Background The “opioid crisis” has been responsible for hundreds of thousands deaths in the US, and is at risk of dissemination worldwide. Within-country studies have demonstrated that the rise of opioid use disorders (OUD) is linked to increased access to opioid prescriptions and to so-called “diseases of despair”. Both have been related to the emergence of globalization policies since the 1980s. First, globalized countries have seen a reorganization of healthcare practices towards quick and easy answers to complex needs, including increased opioid prescriptions. Second, despair has gained those suffering from the mutations of socio-economic systems and working conditions that have accompanied globalization policies (e.g. delocalization, deindustrialization, and the decline of social services). Here, using data with high quality ratings from the Global Burden of Disease database, we evaluated the country-based association between four levels of globalization and the burden of OUD 2019. Results The sample included 87 countries. Taking into account potential country-level confounders, we found that countries with the highest level of globalization were associated with a 31% increase in the burden of OUD 2019 compared to those with the lowest level of globalization (mean log difference: 0.31; 95%CI, 0.04–0.57; p = 0.02). Additional analyses showed a significant effect for low back pain (mean log difference: 0.07; 95%CI, 0.02–0.12; p = 0.007). In contrast, despite sharing some of the risk factors of OUD, other mental and substance use disorders did not show any significant relationship with globalization. Finally, socio-cultural de jure globalization, which compiles indicators related to gender equality, human capital and civil rights, was specifically associated with the burden of OUD (mean log difference: 0.49; 95%CI: 0.23,0.75; p < 0.001). Conclusions These findings suggest that OUD may have inherent underpinnings linked to globalization, and more particularly socio-cultural aspects of globalization. Key factors may be increased rights to access prescriptions, as well as increased feelings of despair related to the erosion of local cultures and widening educational gaps

Imbalance in the sensitivity to different types of rewards in pathological gambling

International audienc

Organization of cognitive control within the lateral prefrontal cortex in schizophrenia.

International audienceCONTEXT: Cognitive control is highly affected in schizophrenia, but its overall functional architecture remains poorly understood. A recent study demonstrated that, in healthy subjects, cognitive control is functionally organized within the lateral prefrontal cortex (LPFC) as a cascade of representations ranging from premotor to anterior LPFC regions according to stimuli, the present perceptual context, and the temporal episode in which stimuli occur. OBJECTIVE: To determine the functional hierarchical organization of cognitive control within the LPFC in patients with schizophrenia. DESIGN: Case-control study. SETTING: Hospital-based research units. PARTICIPANTS: Fifteen schizophrenic patients and 14 controls. MAIN OUTCOME MEASURES: Behavioral performance and regional brain activity as measured by functional magnetic resonance imaging during a task, varying the amount of information conveyed by episodic and contextual signals. RESULTS: In patients and healthy controls, activity in caudal LPFC regions varied as episodic and contextual signals, whereas rostral LPFC regions only exhibited an episodic effect. However, patients made more errors than controls when information conveyed by contextual and episodic signals increased. These impairments were related to hypoactivation in caudal LPFC regions and hyperactivation in rostral LPFC regions, respectively. Activation in caudal LPFC regions negatively correlated with the disorganization syndrome score of patients. CONCLUSIONS: In schizophrenic patients, the architecture of cognitive control follows the cascading organization from rostral LPFC regions to caudal LPFC and premotor regions depending on the temporal framing of action and events. We found, however, that immediate contextual signals insufficiently bias the caudal LPFC activity required to select the appropriate behavioral representation. This specific deficit could thus alter the internal consistency of schizophrenic patients' behavior. To compensate for this weakening of contextual influence, schizophrenic patients may inefficiently use temporal episodic information through higher activation in rostral LPFC regions

The Sequential Binge, a New Therapeutic Approach for Binge Eating: A Pilot Study.

A sizeable proportion of patients experiencing binge eating do not respond to cognitive behavioral therapy (CBT). We present the sequential binge (SB), a new behavioral intervention that complements CBT, and preliminary results of its effects. SB breaks up the binge into repeated identical sequences of eating separated by incremental pauses. This pattern of ingestion aims at facilitating boredom toward the ingested foods and at turning cognitive control away from binge food restriction. SB is hypothesized to reduce food intake during the binge and the number of daily binges.Prospective pilot study. Fifteen binging patients with previous unsuccessful intensive CBT were given SB as an adjunct to their treatment and were followed up for 16 weeks from admission. All patients were reassessed 47 weeks on average after discharge.SB was associated with a 44% relative reduction in the planned food intake (p<0.001), a longer consecutive binge refractory period compared to regular binges (median: 48 hours versus 4 hours, p = 0.002) and an average relative reduction by 26% of binge number the day after each SB (p = 0.004). 47% of patients reached binge abstinence for four consecutive weeks 16 weeks after the first SB.This case series shows promising evidence for the use of SB in patients with refractory binge eating. Further evaluation in a prospective randomized controlled trial would be justified