Cognitive behavioural therapy for obesity and binge eating associated to antipsychotic drugs

Background and Aims: Overweight, obesity and binge eating disorder are commonly reported in persons with severe mental disorders. Particularly, antipsychotic drugs (AP) induce weight gain in up to half of the patients. The aim of the present study is to confirm a previous study results on a larger sample of patients, to assess the impact of the interventions on other relevant dimensions of eating and weight related cognitions as well as to assess potential clinical indicators of outcomes such as AP drug, concomitant treatment with lithium or carbamazepine, psychiatric diagnostic, binge eating and severity of cognitive distortions. Method: A controlled study (12-week CBT vs. B N E) was carried out on 99 patients treated with an AP and who have gained weight following this treatment. Binge eating symptomatology, eating and weight-related cognitions, as well as weight and body mass index were assessed before treatment, at 12 weeks and at 24 weeks. Results: The findings confirms usefulness and effectiveness of the proposed CBT program on the treatment of binge symptomatology, cognitive distortions and obesity in patients treated with AP. Reduction of binge symptoms and maladapted cognitions appeared early, whereas the effect on weight appeared later during the follow up observation. No differences on outcomes were found across pharmacotherapy characteristics, diagnostic categories, binge eating nor severity of cognitive distortions. Conclusion: The proposed CBT treatment is useful for patients suffering from weight gain associated with AP treatments indeed when a concomitant treatment with lithium or valproate was given.

The influence of tobacco consumption on the relationship between schizotypy and hemispheric asymmetry.

Tobacco use is positively associated with severity of symptoms along the schizophrenia spectrum. Accordingly it could be argued that neuropsychological performance, formerly thought to be modulated by schizotypy, is actually modulated by drug use or an interaction of drug use and schizotypy. We tested whether habitual cigarette smokers as compared to non-smokers would show a neuropsychological profile similar to that observed along the schizophrenia spectrum and, if so, whether smoking status or nicotine dependence would be more significant modulators of behavior than schizotypy. Because hemispheric dominance has been found to be attenuated along the schizophrenia spectrum, 40 right-handed male students (20 non-smokers) performed lateralized left- (lexical decisions) and right- (facial decision task) hemisphere dominant tasks. All individuals completed self-report measures of schizotypy and nicotine dependence. Schizotypy predicted laterality in addition to smoking status: While positive schizotypy (Unusual Experiences) was unrelated to hemispheric performance, Cognitive Disorganization predicted reduced left hemisphere dominant language functions. These latter findings suggest that Cognitive Disorganization should be regarded separately as a potentially important mediator of thought disorganization and language processing. Additionally, increasing nicotine dependence among smokers predicted a right hemisphere shift of function in both tasks that supports the role of the right hemisphere in compulsive/impulsive behavior.

The relationship between cognitive errors and interpersonal patterns in depressed women.

Individuals with depression process information in an overly negative or biased way (e.g., Henriques & Leitenberg, 2002) and demonstrate significant interpersonal dysfunction (e.g., Zlotnick, Kohn, Keitner, & Della Grotta, 2000). This study examined the relationship between cognitive errors (CEs) and interpersonal interactions in early psychotherapy sessions of 25 female patients with major depression. Transcripts were rated for CEs using the Cognitive Error Rating Scale (Drapeau, Perry, & Dunkley, 2008). Interpersonal patterns were assessed using the Structural Analysis of Social Behavior (Benjamin, 1974). Significant associations were found between CEs and markers of interpersonal functioning in selected contexts. The implications of these findings in bridging the gap between research and practice, enhancing treatment outcome, and improving therapist training are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

A. Costanza, K. Weber, S. Gandy, C. Bouras, P. R. Hof, P. Giannakopoulos and A. Canuto (2011) Neuropathology and Applied Neurobiology37, 570-584 Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.

Novel action of a wake-promoting neuropeptide in hippocampus : inhibition of nmda receptor function at excitatory synapses through orexin-a

One of the most intriguing functions of the brain is the ability to learn and memorize. The mechanism through which memory and learning are expressed requires the activation of NMDA receptors (NMDARs). These molecular entities are placed at the postsynaptic density of excitatory synapses and their function is tightly controlled by the actions of several modulators at the extracellular, intracellular and pore sites. A large part of the intracellular modulation comes from the action of G-protein coupled receptors (GPCRs). Through intracellular cascades typically involving kinases and phosphatases, GPCRs potentiate or inhibit NMDARs, controlling the conductive state but also the trafficking within the synapse. The GPCRs are involved in the modulation of a variety of brain functions. Many of them control cognition, memory and learning performance, therefore, their effects on NMDARs are extensively studied. The orexinergic system signals through GPCRs and it is well known for the regulation of waking, feeding, reward and autonomic functions. Moreover, it is involved in potentiating hippocampus-related cognitive tasks. Orexin receptors and fibers are present within the hippocampus, but whether these directly modulate hippocampal cells and synapses has not yet been determined. During my thesis, I studied orexinergic actions on excitatory synaptic transmission via whole-cell patch-clamp recordings in rat acute hippocampal slices. I observed that exogenously applied orexin-A (ox-A) exerted a strong inhibitory action on NMDAR-mediated synaptic potentials at mossy fiber (MF)-CA3 synapses, by postsynaptically activating orexin-2 receptors, a minor inhibition at Schaffer collateral-CAl synapses and did not affect other synapses with the CA3 area. Moreover, I demonstrated that the susceptibility of NMDARs to ox- A depends on the tone of endogenous orexin known to fluctuate during the day-night cycle. In fact, in slices prepared during the active period of the rats, when endogenous orexin levels are high, NMDAR-currents were not affected by exogenously applied ox-A. The inhibitory effect of ox-A was, however, reverted when interfering with the orexinergic system through intraperitoneal injections of almorexant, a dual orexin receptor antagonist, during the active phase prior to slice preparation. This thesis work suggests that the orexinergic system regulates NMDAR-dependent information flow through select hippocampal pathways depending on the time-of-day. The specific orexinergic modulation of NMDARs at MFs dampens the excitability of the hippocampal circuit and could impede the mechanisms related to memory formation, possibly also following extended periods of waking. -- La capacité d'apprentissage et de mémorisation est une des fonctions les plus intrigantes de notre cerveau. Il a été montré qu'elles requièrent l'activation des récepteurs NMDA (NMDARs). Ces entités moléculaires sont présentes au niveau de la densité post-synaptique des synapses excitatrices et leur fonction est étroitement contrôlée par l'action de nombreux modulateurs au niveau extracellulaire, intracellulaire et membranaire de ces récepteurs. Une grande partie de la modulation intracellulaire s'effectue via l'action de récepteurs couplés aux protéines G (GPCRs). Grace à leurs cascades intracellulaires typiquement impliquant des kinases et des phosphatases, les GPCRs favorisent l'activation ou l'inhibition des NMDARs, contrôlant ainsi leur perméabilité mais aussi leur mouvement à la synapse. Les GPCRs sont impliquées dans de nombreuses fonctions cérébrales telles que la cognition, la mémoire ainsi que la capacité d'apprentissage c'est pour cela que leurs effets sur les NMDARs sont très étudiés. Le système orexinergique fait intervenir ces GPCRs et est connu par son rôle dans la régulation de fonctions physiologiques telles que l'éveil, la prise alimentaire, la récompense ainsi que d'autres fonctions du système nerveux autonome. De plus, ce système est impliqué dans la régulation de tâches cognitives liées à l'hippocampe. Bien que les fibres et les récepteurs à l'orexine soient présents dans l'hippocampe, leur mécanisme d'action sur les cellules et les synapses de l'hippocampe n'a pas encore été élucidé. Durant ma thèse, je me suis intéressée aux effets de l'orexine sur la transmission synaptique excitatrice en utilisant la méthode d'enregistrement en patch-clamp en configuration cellule entière sur des tranches aiguës d'hippocampes de rats. J'ai observé que l'application exogène d'orexine A d'une part inhibe fortement les courants synaptiques dépendants de l'activation des NMDARs au niveau de la synapse entre les fibres moussues et CA3 via l'activation post-synaptique des orexine récepteurs 2 mais d'autre part n'inhibe que de façon mineure la synapse entre les collatérales de Schaffer et CAI et n'affecte pas les autres synapses impliquant CA3. J'ai également démontré que la sensibilité des NMDARs à l'orexine A dépend de sa concentration endogène qui fluctue durant le cycle éveil-sommeil. En effet, lorsque les coupes d'hippocampes sont préparées durant la période active de l'animal correspondant à un niveau endogène d'orexine élevé, l'application exogène d'orexine A n'a aucun effet sur les courants dépendants de l'activation des NMDARs. Cependant, l'injection dans le péritoine, durant la phase active de l'animal, d'un antagoniste des orexine récepteurs, l'almorexant, va supprimer l'effet inhibiteur de l'orexine A. Les résultats de ma thèse suggèrent donc que le système orexinergique module les informations véhiculées par les NMDARs via des voies de signalisation sélectives de l'hippocampe en fonction du moment de la journée. La modulation orexinergique des NMDARs au niveau des fibres moussues diminue ainsi l'excitabilité du circuit hippocampal et pourrait entraver les mécanismes liés à la formation de la mémoire, potentiellement après de longues périodes d'éveil.

Adapter and enzymatic functions of proteases in T-cell activation.

Proteases control many vital aspects of humoral and cellular immune responses, including the maturation of cytokines and the killing of target cells. Recently, it has become evident that triggering of the T-cell receptor controls T-cell proliferation through proteases such as mucosa-associated lymphoid tissue 1 (MALT1) and Caspase-8 that act both as adapters and enzymes. Here, we discuss the role of these and other proteases that are relevant to the control of the T-cell response and represent interesting targets of therapeutic immunomodulation.

On the relationship between performance-approach goals and cognitive performance : when the desire to outperform others becomes interfering

Cette thèse explore dans quelle mesure la poursuite d'un but de performance-approche (i.e., le désir de surpasser autrui et de démontrer ses compétences) favorise, ou au contraire endommage, la réussite et l'apprentissage-une question toujours largement débattue dans la littérature. Quatre études menées en laboratoire ont confirmé cette hypothèse et démontré que la poursuite du but de performance-approche amène les individus à diviser leur attention entre d'une part la réalisation de la tâche évaluée, et d'autre part la gestion de préoccupations liées à l'atteinte du but-ceci empêchant une concentration efficace sur les processus de résolution de la tâche. Dans une deuxième ligne de recherche, nous avons ensuite démontré que cette distraction est exacerbée chez les individus les plus performants et ayant le plus l'habitude de réussir, ceci dérivant d'une pression supplémentaire liée au souhait de maintenir le statut positif de « bon élève ». Enfin, notre troisième ligne de recherche a cherché à réconcilier ces résultats-pointant l'aspect distractif du but de performance-approche-avec le profil se dégageant des études longitudinales rapportées dans la littérature-associant ce but avec la réussite académique. Ainsi, nous avons mené une étude longitudinale testant si l'adoption du but de performance-approche en classe pourrait augmenter la mise en oeuvre de stratégies d'étude tactiquement dirigées vers la performance-favorisant une réussite optimale aux tests. Nos résultats ont apporté des éléments en faveur de cette hypothèse, mais uniquement chez les élèves de bas niveau. Ainsi, l'ensemble de nos résultats permet de mettre en lumière les processus cognitifs à l'oeuvre lors de la poursuite du but de performance-approche, ainsi que d'alimenter le débat concernant leur aspect bénéfique ou nuisible en contexte éducatif. -- In this dissertation, we propose to investigate whether the pursuit of performance-approach goals (i.e., the desire to outperform others and appear talented) facilitates or rather endangers achievement and learning-an issue that is still widely discussed in the achievement goal literature. Four experiments carried out in a laboratory setting have provided evidence that performance- approach goals create a divided-attention situation that leads cognitive resources to be divided between task processing and the activation of goal-attainment concerns-which jeopardizes full cognitive immersion in the task. Then, in a second research line, we found evidence that high- achievers (i.e., those individuals who are the most used to succeed) experience, under evaluative contexts, heightened pressure to excel at the task, deriving from concerns associated with the preservation of their "high-achiever" status. Finally, a third research line was designed to try to reconcile results stemming from our laboratory studies with the overall profile emerging from longitudinal research-which have consistently found performance-approach goals to be a positive predictor of students' test scores. We thus set up a longitudinal study so as to test whether students' adoption of performance-approach goals in a long-term classroom setting enhances the implementation of strategic study behaviors tactically directed toward goal-attainment, hence favoring test performance. Our findings brought support for this hypothesis, but only for low-achieving students. Taken together, our findings shed new light on the cognitive processes at play during the pursuit of performance-approach goals, and are likely to fuel the debate regarding whether performance-approach goals should be encouraged or not in educational settings.

Effects of cognitive abilities on metapopulation connectivity

Connectivity among demes in a metapopulation depends on both the landscape's and the focal organism's properties (including its mobility and cognitive abilities). Using individual-based simulations, we contrast the consequences of three different cognitive strategies on several measures of metapopulation connectivity. Model animals search suitable habitat patches while dispersing through a model landscape made of cells varying in size, shape, attractiveness and friction. In the blind strategy, the next cell is chosen randomly among the adjacent ones. In the near-sighted strategy, the choice depends on the relative attractiveness of these adjacent cells. In the far-sighted strategy, animals may additionally target suitable patches that appear within their perceptual range. Simulations show that the blind strategy provides the best overall connectivity, and results in balanced dispersal. The near-sighted strategy traps animals into corridors that reduce the number of potential targets, thereby fragmenting metapopulations in several local clusters of demes, and inducing sink-source dynamics. This sort of local trapping is somewhat prevented in the far-sighted strategy. The colonization success of strategies depends highly on initial energy reserves: blind does best when energy is high, near-sighted wins at intermediate levels, and far-sighted outcompetes its rivals at low energy reserves. We also expect strong effects in terms of metapopulation genetics: the blind strategy generates a migrant-pool mode of dispersal that should erase local structures. By contrast, near- and far-sighted strategies generate a propagule-pool mode of dispersal and source-sink behavior that should boost structures (high genetic variance among- and low variance within local clusters of demes), particularly if metapopulation dynamics is also affected by extinction-colonization processes. Our results thus point to important effects of the cognitive ability of dispersers on the connectivity, dynamics and genetics of metapopulations.

Cognitive impairment in elderly medical inpatients: detection and associated six-month outcomes.

OBJECTIVE: The authors examined the relationship of cognitive impairment at hospital admission to 6-month outcome (hospital readmission, nursing home admission, and death) in a cohort of elderly medical inpatients. METHODS: A group of 401 medical inpatients age 75 and older underwent a comprehensive geriatric assessment at hospital admission and were followed up for 6 months. Cognitive impairment was defined as a score <24 on the Mini-Mental State Exam. Detection was assessed through blinded review of discharge summary. Follow-up data were gathered from the centralized billing system (hospital and nursing home admissions) and from proxies (death). RESULTS: Cognitive impairment was present in 129 patients (32.3%). Only 48 (37.2%) were detected; these had more severe impairment than undetected cases. During follow-up, cognitive impairment, whether detected or not, was associated with death and nursing home admission. After adjustment for health, functional, and socioeconomic status, an independent association remained only for nursing home admission in subjects with detected impairment. Those with undetected impairment appeared to be at intermediate risk, but this relationship was not statistically significant. CONCLUSION: In these elderly medical inpatients, cognitive impairment was frequent, rarely detected, and associated with nursing home admission during follow-up. Although this association was stronger in those with detected impairment, these results support the view that acute hospitalization presents an opportunity to better detect cognitive impairment in elderly patients and target further interventions to prevent adverse outcomes such as nursing home admission.

MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis.

Despite that cognitive impairment is a known early feature present in multiple sclerosis (MS) patients, the biological substrate of cognitive deficits in MS remains elusive. In this study, we assessed whether T1 relaxometry, as obtained in clinically acceptable scan times by the recent Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) sequence, may help identifying the structural correlate of cognitive deficits in relapsing-remitting MS patients (RRMS). Twenty-nine healthy controls (HC) and forty-nine RRMS patients underwent high-resolution 3T magnetic resonance imaging to obtain optimal cortical lesion (CL) and white matter lesion (WML) count/volume and T1 relaxation times. T1 z scores were then obtained between T1 relaxation times in lesion and the corresponding HC tissue. Patient cognitive performance was tested using the Brief Repeatable Battery of Neuro-psychological Tests. Multivariate analysis was applied to assess the contribution of MRI variables (T1 z scores, lesion count/volume) to cognition in patients and Bonferroni correction was applied for multiple comparison. T1 z scores were higher in WML (p < 0.001) and CL-I (p < 0.01) than in the corresponding normal-appearing tissue in patients, indicating relative microstructural loss. (1) T1 z scores in CL-I (p = 0.01) and the number of CL-II (p = 0.04) were predictors of long-term memory; (2) T1 z scores in CL-I (β = 0.3; p = 0.03) were independent determinants of long-term memory storage, and (3) lesion volume did not significantly influenced cognitive performances in patients. Our study supports evidence that T1 relaxometry from MP2RAGE provides information about microstructural properties in CL and WML and improves correlation with cognition in RRMS patients, compared to conventional measures of disease burden.