Investigation of the relation between substance use and cognitive performance and its mediating effect on psychopathology symptoms

Le projet de thèse porte sur la consommation de substances psychoactives chez les adolescents et le lien séquentiel entre la consommation de drogues, la performance cognitive, et la santé mentale des jeunes. Les objectifs de la thèse sont : 1) de tester la relation entre la prise de cannabis, ou d’alcool, et la performance cognitive, et d’en observer la séquence, 2) de vérifier si la relation entre la consommation et la performance cognitive permet, en partie, de comprendre l’apparition de symptômes de psychopathologie chez les jeunes, et 3) de définir les pratiques les mieux fondées empiriquement pour prévenir la consommation de substances chez les adolescents. Le premier chapitre de la thèse évalue la relation et la séquence entre les habitudes de consommation d’environ 4000 jeunes de la région métropolitaine de Montréal (Qc, Canada) et la trajectoire de leur développement cognitif sur une période de quatre ans. Dans un deuxième chapitre, la thèse évalue comment la relation entre la consommation et la performance cognitive de ces mêmes jeunes peut expliquer, sur une période de cinq ans, une partie de la relation observée entre la consommation et l’apparition de symptômes de psychopathologie. Dans un dernier chapitre, la thèse fait la revue des données portant sur trois types d’interventions préventives afin d’identifier comment la recherche empirique peut bonifier les efforts de prévention de la toxicomanie chez les adolescents. Les données ont été extraites d’une cohorte d’adolescents issus de la population générale, suivis longitudinalement, dans le cadre de l’étude Co-Venture (n = 3826, âgés de 12 ans à l’admission dans l’étude, suivis annuellement pendant 5 ans). Les résultats ont démontré que, bien que certains facteurs semblent prédisposer un sous-groupe de jeunes à une consommation hâtive ainsi que des difficultés neuropsychologiques, la consommation de drogues, notamment de cannabis, semble liée, de façon à la fois ponctuelle et durable, à un délai du développement cognitif, plus particulièrement des fonctions exécutives. Cette association avec le cannabis semble, en faible partie, jouer un rôle médiateur dans la relation qui unit cette consommation et l’émergence de symptômes de psychopathologie chez les adolescents. Toutefois, des facteurs prédisposants semblent contribuer à l’association entre ces trois variables. Bien que la recherche identifie que plusieurs programmes de prévention peuvent être efficaces, la majorité d’entre eux présentent des effets modestes et ponctuels. Les programmes les plus probants semblent s’inscrire dans le registre des approches de prévention ciblées. Pour bonifier nos méthodes de prévention de la toxicomanie chez les adolescents, nous pourrions tenir compte de certains facteurs prédisposants et les utiliser comme cible d’intervention; par exemple, le fonctionnement cognitif basal pourrait constituer une piste intéressante. De plus, le tempérament ou la personnalité semblent mieux établis pour prévenir la consommation de façon durable et pour aborder les enjeux cognitifs et psychologiques associés à la consommation abusive de substances. Mots-clés : Alcool, cannabis, adolescence, fonctions cognitives, symptômes de psychopathologie, devis longitudinaux, médiation, préventionThis thesis project addresses adolescents’ substance misuse and the sequential link between drug use, cognitive performance, and mental health outcomes in youth. The objectives of this thesis are: 1) to test the relation and sequence between cannabis or alcohol use and cognitive outcomes, 2) to verify if the relation between substance use and cognitive outcomes could help understand, in part, why young substance users report psychopathology symptoms, and 3) to review evidence-based interventions to prevent adolescent substance misuse and to assess what contribution could stem from the collected empirical data. The first chapter of this thesis assesses the relation and sequence between substance use behaviour of nearly 4000 youth from the Montreal metropolitan area (QC, Canada) and their cognitive development over four years. In a second chapter, this thesis analyzes how the association between substance use and cognitive outcomes could partially explain, over five years, the link observed between substance use and the appearance of psychopathology symptoms. In a final chapter, this thesis reviews data surrounding three types of preventative interventions to identify how empirical research could improve addiction prevention strategies. The data was extracted from a group of adolescents issued from the general population followed longitudinally in the scope of the Co-Venture study (n = 3826, from 12 years of age upon admission to the study, followed up annually for a period of five years). The results demonstrated that, although certain factors seem to predispose a sub-group of young people to early consumption and neuropsychological difficulties, drug consumption, especially cannabis consumption, seem to reliably predict a delay in the development of cognitive faculties, particularly the executive functions of the brain. This association with cannabis appears, to a small extent, to partially mediate the link already observed between said consumption and the emergence of psychopathology symptoms in adolescents. Still, predisposing factors seem to contribute to the association between these three variables. Although research would appear to show that several prevention strategies could be effective, most of them present modest and punctual results. The best-substantiated programs appeared to be those that adhered to a targeted prevention approach. To improve our methods of substance use prevention, one could take predisposing factors into account and use them to inform specialized intervention. Baseline cognitive functioning could constitute a particularly promising avenue. All the same, certain predisposing factors such as temperament or personality seem better equipped to prevent early-onset substance misuse and to address the psychological and cognitive issues associated with adolescent substance intake. To improve addiction prevention methods in adolescents, one could factor into account predisposing factors and use them to inform specialized intervention; for example, baseline cognitive functioning could constitute a promising avenue. In addition, temperament or personality traits seem better established to prevent early-onset substance use and to address the psychological and cognitive issues associated with adolescents’ substance misuse. Key words: Alcohol, cannabis, adolescence, cognitive functions, psychopathology symptoms, longitudinal data, mediation, preventio

Occlusion of LTP-Like Plasticity in Human Primary Motor Cortex by Action Observation

Passive observation of motor actions induces cortical activity in the primary motor cortex (M1) of the onlooker, which could potentially contribute to motor learning. While recent studies report modulation of motor performance following action observation, the neurophysiological mechanism supporting these behavioral changes remains to be specifically defined. Here, we assessed whether the observation of a repetitive thumb movement – similarly to active motor practice – would inhibit subsequent long-term potentiation-like (LTP) plasticity induced by paired-associative stimulation (PAS). Before undergoing PAS, participants were asked to either 1) perform abductions of the right thumb as fast as possible; 2) passively observe someone else perform thumb abductions; or 3) passively observe a moving dot mimicking thumb movements. Motor evoked potentials (MEP) were used to assess cortical excitability before and after motor practice (or observation) and at two time points following PAS. Results show that, similarly to participants in the motor practice group, individuals observing repeated motor actions showed marked inhibition of PAS-induced LTP, while the “moving dot” group displayed the expected increase in MEP amplitude, despite differences in baseline excitability. Interestingly, LTP occlusion in the action-observation group was present even if no increase in cortical excitability or movement speed was observed following observation. These results suggest that mere observation of repeated hand actions is sufficient to induce LTP, despite the absence of motor learning

Quorum Sensing Signaling Molecules Produced by Reference and Emerging Soft-Rot Bacteria (Dickeya and Pectobacterium spp.)

International audienceBACKGROUND: Several small diffusible molecules are involved in bacterial quorum sensing and virulence. The production of autoinducers-1 and -2, quinolone, indole and γ-amino butyrate signaling molecules was investigated in a set of soft-rot bacteria belonging to six Dickeya or Pectobacterium species including recent or emerging potato isolates. METHODOLOGY/PRINCIPAL FINDINGS: Using bacterial biosensors, immunoassay, and chromatographic analysis, we showed that soft-rot bacteria have the common ability to produce transiently during their exponential phase of growth the N-3-oxo-hexanoyl- or the N-3-oxo-octanoyl-l-homoserine lactones and a molecule of the autoinducer-2 family. Dickeya spp. produced in addition the indole-3-acetic acid in tryptophan-rich conditions. All these signaling molecules have been identified for the first time in the novel Dickeya solani species. In contrast, quinolone and γ-amino butyrate signals were not identified and the corresponding synthases are not present in the available genomes of soft-rot bacteria. To determine if the variations of signal production according to growth phase could result from expression modifications of the corresponding synthase gene, the respective mRNA levels were estimated by reverse transcriptase-PCR. While the N-acyl-homoserine lactone production is systematically correlated to the synthase expression, that of the autoinducer-2 follows the expression of an enzyme upstream in the activated methyl cycle and providing its precursor, rather than the expression of its own synthase. CONCLUSIONS/SIGNIFICANCE: Despite sharing the S-adenosylmethionine precursor, no strong link was detected between the production kinetics or metabolic pathways of autoinducers-1 and -2. In contrast, the signaling pathway of autoinducer-2 seems to be switched off by the indole-3-acetic acid pathway under tryptophan control. It therefore appears that the two genera of soft-rot bacteria have similarities but also differences in the mechanisms of communication via the diffusible molecules. Our results designate autoinducer-1 lactones as the main targets for a global biocontrol of soft-rot bacteria communications, including those of emerging isolates

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Les conduites alimentaires hivernales dans le rayon de Roquefort modifient la composition chimique du lait de brebis

National audienc

Brebis laitière : Une alimentation adaptée

4 illus. Numéro spécial laitNational audienc

Soil charcoal to assess the impacts of past human disturbances on tropical forests

The canopy of many central African forests is dominated by light-demanding tree species that do not regenerate well under themselves. The prevalence of these species might result from ancient slash-and-burn agricultural activities that created large openings, while a decline of these activities since the colonial period could explain their deficit of regeneration. To verify this hypothesis, we compared soil charcoal abundance, used as a proxy for past slash-and-burn agriculture, and tree species composition assessed on 208 rainforest 0.2 ha plots located in three areas from Southern Cameroon. Species were classified in regeneration guilds (pioneer, non-pioneer light-demanding, shade-bearer) and characterized by their woodspecific gravity, assumed to reflect light requirement. We tested the correlation between soil charcoal abundance and: (i) the relative abundance of each guild, (ii) each species and family abundance and (iii) mean wood-specific gravity. Charcoal was found in 83% of the plots, indicating frequent past forest fires. Radiocarbon dating revealed two periods of fires: ‘‘recent’’ charcoal were on average 300 years old (up to 860 BP, n = 16) and occurred in the uppermost 20 cm soil layer, while ‘‘ancient’’ charcoal were on average 1900 years old (range: 1500 to 2800 BP, n = 43, excluding one sample dated 9400 BP), and found in all soil layers. While we expected a positive correlation between the relative abundance of light demanding species and charcoal abundance in the upper soil layer, overall there was no evidence that the current heterogeneity in tree species composition can be explained by charcoal abundance in any soil layer. The absence of signal supporting our hypothesis might result from (i) a relatively uniform impact of past slash-and-burn activities, (ii) pedoturbation processes bringing ancient charcoal to the upper soil layer, blurring the signal of centuries-old Human disturbances, or (iii) the prevalence of other environmental factors on species composition