Behavioural alteration in chronic pain: are brain glia involved?

Behavioural symptoms such as abnormal emotionality (including anxious and depressive episodes) and cognition (for instance weakened decision-making) are highly frequent in both chronic pain patients and their animal models. The theory developed in the present article posits that alterations in glial cells (astrocytes and microglia) in cortical and limbic brain regions might be the origin of such emotional and cognitive chronic pain-associated impairments. Indeed, in mood disorders (unipolar depression, anxiety disorders, autism or schizophrenia) glial changes in brain regions involved in mood control (prefrontal and cingulate cortices, amygdala and the hippocampus) have been recurrently described. Besides, glial cells have been undoubtedly identified as key actors in the sensory component of chronic pain, owing to the profound phenotypical changes they undergo throughout the sensory pathway. Hence, the possibility arises that brain astrocytes and microglia react in upper brain structures as well, mediating the related mood and cognitive dysfunctions in chronic pain. So far, only very few studies have provided results in this prospect, mainly indirectly in pain-independent researches. Nevertheless, the first scant available data seem to merge in a unified description of a brain glial reaction occurring after chronic peripheral lesion. The present article uses this scarce literature to formulate the provocative theory of a glia-driven mood and cognitive dysfunction in chronic pain, expounding upon its validity and putative therapeutical impact as well as its current limitations and expected future developments.

Analgesic efficacy of intravenous perfusion of lidocaine, ketamine or a combination after laparotomy in a placebo-controlled, randomized, double-blind prospective study

In acute postoperative pain management intravenous lidocaine and/or ketamine have been advocated because of their morphine-sparing effect. The goal of this prospective, randomised, double-blind study was to assess morphine consumption with different regimens of intravenous infusion of lidocaine, ketamine or both during 48 hours following laparotomy. Patients were randomised into four groups. Group L, K, and KL received intravenous lidocaine, ketamine or a combination, respectively, before incision and during 48 hours postoperatively. The control group (C) received a similar volume of saline bolus and infusion. Postoperative analgesia included morphine delivered by a patient-controlled analgesia device. Primary outcome was the cumulative morphine consumption and pain, sedation scores, pressure algometry and side effects were our secondary outcomes. Cognition and psychomotor performance were also tested. Out of 57 eligible patients, 44 completed the study. Lidocaine reduced the cumulative morphine consumption compared with the control group (mean 0.456 mg.kg-1 +/- 0.244 (SD) versus 0.705 +/- 0.442, respectively, Ρ < 0.001). Pain scores during movement were statistically lower in all three treatment groups. Psychometric tests showed that the lidocaine group expressed more depressed feelings and sadness compared to the control group. Lidocaine administration had a morphine-sparing effect with a 36% reduction of morphine consumption while ketamine alone or combined with lidocaine did not. As a whole, our results suggest that intravenous lidocaine may offer advantages for postoperative analgesia. We propose lidocaine as a new alternative for pain control that needs to be studied further in future multicentric studies.

Troubles cognitifs du patient alcoolo-dépendant. Dépistage et examen neuropsychologique [Cognitive impairment in alcohol addiction].

Alcohol addiction is associated with cognitive impairment of clinically varying intensity and duration, which starts progressively while remaining often underestimated. Progressive brain damage can lead over time to a dementia syndrome. The diagnosis of cognitive deficits is of prime importance since it helps to optimize patient care and to decrease failure in re-insertion programs. Here we propose several screening tests which should give the practitioner the opportunity to make a basic cognitive assessment and to decide whether a comprehensive neuropsychological evaluation is indicated. In alcohol addiction cognitive impairment is dominated by executive dysfunction of varying severity, which is also characteristic of alcohol dementia.

The impact of personality characteristics on the clinical expression in neurodegenerative disorders--a review.

Clinical experience suggests that longstanding personality characteristics as a person's most distinctive features of all are likely to play a role in how someone with dementia copes with his increasing deficiencies. Personality characteristics may have a pathoplastic effect on both behavioral and psychological symptoms (BPS) or on cognition as well as cognitive decline. Cognitive disorders accompanied by BPS are a tremendous burden for both the patient and their proxies. This review suggests that premorbid personality characteristics are co-determinants of BPS in cognitive disorders, but much effort is needed to clarify whether or not specific premorbid personality traits are associated with specific BPS as no strong links have so far emerged. This review further shows that a growing field of research is interested in the links not only between quite short-lived emotional states and cognitive processes, but also between longstanding personality traits and cognition in both healthy individuals and patients with neurodegenerative disorders. Furthermore, a few studies found that specific premorbid personality traits may be risk factors for neurodegenerative diseases. However, research findings in this area remain scarce despite a huge literature on personality and cognitive disorders in general. An important shortcoming that hampers so far the progress of our understanding in these domains is the confusion in the literature between longstanding premorbid personality traits and transient personality changes observed in neurodegenerative diseases. Few studies have based their assessments on accepted personality theories and carefully investigated premorbid personality traits in patients with cognitive disorders, although assessing personality may be complicated in these patients. Studying the impact of personality characteristics in cognitive disorders is an especially promising field of research in particular when concomitantly using neurobiological approaches, in particular structural brain imaging and genetic studies as suggested by as yet rare studies. Improved understanding of premorbid personality characteristics as determinants of both BPS or cognitive capacities or decline is likely to influence our attitudes towards the treatment of demented patients and ultimately to help in alleviating a patient's and their proxies' burden.

A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.

Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.

Regulação do sector farmacêutico em Cabo Verde: o desafio da criação de uma agência de regulação

O medicamento é uma tecnologia cuja importância é indiscutível seja para a saúde, como enquanto factor económico de crescimento e desenvolvimento. A sua regulação está fundamentada acrescidos os factores da sua essencialidade, da assimetria de informação, da cadeia de intermediários, dos interesses financeiros, dos requisitos para a demonstração de eficácia e segurança e as normas para promover a sua utilização eficiente. O Estado tem diversas abordagens possíveis para a regulação farmacêutica que implica sempre a existência de uma estrutura orgânica que assuma as atribuições de forma eficaz e eficiente. Este trabalho discute o modelo de regulação farmacêutica para as condições específicas de Cabo Verde usando como linhas de pesquisa (1) o enquadramento geral da prática de regulação a nível internacional, as recomendações da OMS e os países de referência no âmbito da Comunidade dos Países de Língua Oficial Portuguesa para procurar caracterizar esse processo, identificar as diferenças entre a regulação implementada em países mais desenvolvidos e os países em desenvolvimento e decidir se as agências de regulação podem ser vistas como uma transferência de tecnologia de gestão; (2) o modelo de institucionalização da regulação farmacêutica previsto para Cabo Verde e aquele que foi na prática implementado, com ênfase nas competências, estratégia de intervenção e constrangimentos, para por fim (3) proceder-se à elaboração de uma apreciação crítica, sob o pano de fundo da harmonização técnica e normativa, retomando as recomendações da OMS, a prática internacional neste contexto, corporizada pelos casos da experiência no Brasil e em Portugal e o modelo conceptualizado, relacionando as disparidades com os constrangimentos identificados. Feita a apreciação crítica propõe-se um novo modelo de regulação fazendo referência à revisão dos estatutos da autoridade reguladora e a alterações do figurino institucional.

Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy.

The onset of epilepsy in brain systems involved in social communication and/or recognition of emotions can occasionally be the cause of autistic symptoms or may aggravate preexisting autistic symptoms. Knowing that cognitive and/or behavioral abnormalities can be the presenting and sometimes the only symptom of an epileptic disorder or can even be caused by paroxysmal EEG abnormalities without recognized seizures, the possibility that this may apply to autism has given rise to much debate. Epilepsy and/or epileptic EEG abnormalities are frequently associated with autistic disorders in children but this does not necessarily imply that they are the cause; great caution needs to be exercised before drawing any such conclusions. So far, there is no evidence that typical autism can be attributed to an epileptic disorder, even in those children with a history of regression after normal early development. Nevertheless, there are several early epilepsies (late infantile spasms, partial complex epilepsies, epilepsies with CSWS, early forms of Landau-Kleffner syndrome) and with different etiologies (tuberous sclerosis is an important model of these situations) in which a direct relationship between epilepsy and some features of autism may be suspected. In young children who primarily have language regression (and who may have autistic features) without evident cause, and in whom paroxysmal focal EEG abnormalities are also found, the possible direct role of epilepsy can only be evaluated in longitudinal studies.

Les troubles psychiatriques des patients âgés avec une maladie de Parkinson et leurs traitements [Psychiatric disorders in elderly patients with Parkinson's disease and their treatments].

Parkinson's disease (PD) is a neuropsychiatric disorder. During the course of PD, most patients develop at least one psychiatric syndrome. Depression is the most frequent disorder and affects nearly half of all patients. The use of an increasing number of new drugs, in particular the dopaminergic agents, puts these patients at risk of developing both delirium and psychosis. This article summarizes the different psychiatric syndromes seen in PD and gives an account of the various treatment possibilities.

Endogenous bargaining power

We present a novel approach to N-person bargaining, based on the idea thatthe agreement reached in a negotiation is determined by how the directconflict resulting from disagreement would be resolved. Our basic buildingblock is the disagreement function, which maps each set of feasible outcomesinto a disagreement point. Using this function and a weak axiom basedon individual rationality we reach a unique solution: the agreement inthe shadow of conflict, ASC. This agreement may be construed as the limitof a sequence of partial agreements, each of which is reached as a functionof the parties relative power. We examine the connection between ASC andasymmetric Nash solutions. We show the connection between the power ofthe parties embodied in the ASC solution and the bias in the SWF thatwould select ASC as an asymmetric Nash solution.

The political economy of employment protection

This paper develops a model of job creation and job destruction in agrowing economy with embodied technical progress, that we use toanalyze the political support for employment protection legislationssuch as the ones that are observed in most European countries.We analyze the possibility of Condorcet cycles due to the fact thatworkers about to become unemployed prefer both an increase and areduction in firing costs over the status quo. Despite this problem, we show the existence of local, and sometimes global majority winners.In voting in favour of employment protection, incumbent employeestrade off lower living standards (because employment protectionmaintains workers in less productive activities) against longer job duration. We show that the gains from, and consequently the politicalsupport for employment protection (as defined by maximunjob tenure) are larger, the lower the rate of creative destruction and the largerthe worker's bargaining power. Numerical simulations suggest a hump-shaped response of firing costs to these variables, as well as negative impact of exogeneous turnover on employment protection.

Comparison of potential adjustment variables representing primary intellectual level in epidemiological studies on neurotoxicity

BACKGROUND: Primary intellectual abilities (PIA) are a confounder in epidemiological studies on neurotoxicity. A good measure of this confounder should be independent of age as PIA is an intrinsic ability. Furthermore, as PIA is related to health endpoints, any measure of PIA should reveal this association. This study is aimed at comparing vocabulary test, diploma and age at end of schooling properties as measures of PIA in a non-exposed population of workers. METHODS: The design was a cross-sectional study of 413 non-exposed workers (203 women and 210 men) selected from a health check-up center. The effect of age on the vocabulary score was assessed using an analysis of covariance adjusted for diploma. Relationships between neuropsychological performances and vocabulary score, diploma and end of schooling age were, respectively, assessed using multiple linear regressions adjusted for age and gender. RESULTS: Vocabulary score increased significantly with age, both for men and women. The increase was 0.14 word per year for women, and 0.18 word per year for men. The explained variance of the models evaluating the relationships between age at end of schooling, diploma, vocabulary test, and neuropsychological performances was quite similar for the three measures of PIA. CONCLUSIONS: Vocabulary score was found to be age-related, even after adjustment for diploma. No difference was found between these three variables in terms of their relationship to neuropsychological endpoints. Moreover, the literature shows that vocabulary test performances are influenced by exposure to neurotoxic agents. These results suggest that vocabulary score could be of interest for participants of similar ages and similar diplomas. Otherwise, the other two variables would be better PIA measures in neurotoxicology studies.

Human nature and institutional analysis

This essay reviews some findings in cognition sciences and examines their consequences for the analysis of institutions. It starts by exploring how humans specialization in producing knowledge ensures our success in dominating the environment but also changes fast our environment. So fast that it did not give time to natural selection to adapt our biology, causing it to be potentially maladapted in important dimensions. A main function of institutions is therefore to fill the gap between the demands of our relatively new environment and our biology, still adapted to our ancestral environment as hunter-gatherers. Moreover, institutions are built with the available elements, which include our instincts. A deeper understanding of both aspects, their adaptive function and this recruitment of ancestral instincts, will add greatly to our ability to manage institutions.

Homéostasie, marqueurs somatiques et intentionnalité : le statut de la représentation et ses implications en psychanalyse et en neuroscience

Résumé : Si la psychanalyse est régulièrement remise en cause pour son manque de fondement scientifique, de nombreux travaux issus des neurosciences en appellent paradoxalement à un retour aux thèses freudiennes. Cette étude se propose, dans ce contexte, de revisiter les bases neurobiologiques de la métapsychologie et de montrer comment celle-ci repose sur une conception homéostatique du vivant. On en tire plusieurs conséquences. Premièrement, contre Brentano, selon qui l'intentionnalité est la marque du psychologique, on propose que celle-ci s'avère être, plus originellement, la marque des régulations biologiques. Deuxièmement, on montre comment Freud et Damasio développent des conceptions similaires sur le fonctionnement homéostatique de la cognition. Sur le plan épistémologique, on plaide en faveur de la complémentarité de ces deux approches. Si Damasio met au jour les variables somatiques permettant de mesurer les effets de la vie psychique, la théorie pulsionnelle permet de dépasser les problèmes liés à l'ambiguïté de la notion de «représentation cérébrale ». C'est à partir de cette thèse que l'on peut, selon nous, appréhender la psychanalyse comme un double projet visant à articuler une naturalisation de l'appareil psychique à une herméneutique de ses productions. On considère cette double visée comme une réponse à la difficulté centrale que rencontrent les sciences de l'esprit quant aux conditions de possibilité d'une naturalisation de l'intentionnalité. A partir de cette problématique, il devient pertinent d'évaluer la solution freudienne à la lumière de la posture intentionnelle dennettienne et de la théorie gazzaniguienne de l'interpreter. II ne s'agit pas, selon ces dernières approches, de naturaliser directement l'intentionnalité, au risque de commettre une erreur de catégorie. Il est question, au contraire, d'utiliser les principes du fonctionnement homéostatique comme autant de «règles »interprétatives permettant, sur le plan psychologique, de construire du sens. On trouve enfin dans le modèle de l'espace global de travail un moyen de remettre au goût du jour la conception freudienne, dynamique et conflictuelle, du fonctionnement psychique. On avance enfin, à partir de ce modèle, des hypothèses sur les mécanismes cérébraux susceptibles de sous-tendre l'efficacité thérapeutique de la cure analytique. Abstract : While Psychoanalysis' scientific basis is open to question, some neuroscience works are paradoxically calling for a return to Freud. Therefore, the first aim of our study consists in revisiting metapychology's neurobiological roots and to show how it is grounded on a homeostatic theory of life. Several consequences can be drawn from this statement. Firstly, in opposition to Brentanian definition of intentionality, as the specific mark of psychology, we argue that it is more specifically the mark of biological balance. Secondly, this statement allows to show how Freud's and Damasio's theories share common views on the homeostatic functioning of cognition. From an epistemological point of view, they complete one another. If Damasio has highlighted the measurable somatic variables from which we can infer psychic life, the theory of drives allows conceptual difficulties linked to the use of the ambiguous notion of "cerebral representation" to be overcome. According to us, this thesis leads psychoanalysis to be approached as a twin project aiming to articulate psyche naturalization, to a hermeneutic of its productions. It maybe seen as a way to respond to the central issue of mind sciences, that is, to account for the naturalization of intentionality. Given this theoretical framework, it seems relevant to reconsider freudism in the light of the dennettian intentional stance and the gazzanigan theory of interpreter. Then, freudism can be seen as a way to avoid a category mistake. Its solution rejects direct intentionality naturalization in favor of a construction of sense. In this framework, interpretation is regulated by the rules abstracted from the homeostatic functioning of life. Furthermore, we show how the dynamic and conflictual Freudian psyche can be evaluated using the Global workspace model, which allows us to put forth hypotheses on the cerebral mechanisms that may underlie the efficiency of analytical cure.

An Overview of the association between schizotypy and dopamine

Schizotypy refers to a constellation of personality traits that are believed to mirror the subclinical expression of schizophrenia in the general population. Evidence from pharmacological studies indicates that dopamine is involved in the aetiology of schizophrenia. Based on the assumption of a continuum between schizophrenia and schizotypy, researchers have begun investigating the association between dopamine and schizotypy using a wide range of methods. In this article, we review published studies on this association from the following areas of work: (1) Experimental investigations of the interactive effects of dopaminergic challenges and schizotypy on cognition, motor control and behaviour, (2) dopaminergically supported cognitive functions, (3) studies of associations between schizotypy and polymorphisms in genes involved in dopaminergic neurotransmission, and (4) molecular imaging studies of the association between schizotypy and markers of the dopamine system. Together, data from these lines of evidence suggest that dopamine is important to the expression and experience of schizotypy and associated behavioural biases. An important observation is that the experimental designs, methods, and manipulations used in this research are highly heterogeneous. Future studies are required to replicate individual observations, to enlighten the link between dopamine and different schizotypy dimensions (positive, negative, cognitive disorganisation), and to guide the search for solid dopamine-sensitive behavioural markers. Such studies are important in order to clarify inconsistencies between studies. More work is also needed to identify differences between dopaminergic alterations in schizotypy compared to the dysfunctions observed in schizophrenia.