Dimorphisme sexuel dans la schizophrénie

Récemment, des études neuroanatomiques ont suggéré une inversion du dimorphisme sexuel normal chez les personnes schizophrènes dans plusieurs structures limbiques et corticolimbiques, impliquées dans le fonctionnement émotionnel. Stimulée par ces études, nous avons analysé des données provenant de quinze hommes et de dix femmes, ayant un diagnostic de la schizophrénie, qui avaient été mesurés par l’imagerie en résonance magnétique fonctionnelle (IRMf) pendant l’exposition à deux tâches émotionnelles. En général, les deux essais ont évoqué des activations cérébrales beaucoup plus étendues et plus intenses chez les hommes que chez les femmes. L’échantillon des résultats obtenus diffère de manière significative de ce qui avait été observé dans la population générale. Ces résultats apportent un soutien à la suggestion d’une « masculinisation » des femmes et d’une « féminisation » des hommes ayant un diagnostic de schizophrénie. Une recherche auprès d’un plus grand nombre de patients et de sujets contrôles est actuellement en cours pour confirmer cette hypothèse.Recent neuroanatomical studies imply a reversal of normal sexual dimorphism in schizophrenia in several corticolimbic structures, including the anterior cingulate, orbitofrontal cortex and amygdala. Prompted by these reports we have analyzed data of fifteen men and ten women with the diagnosis of schizophrenia who underwent functional magnetic resonance imaging (fMRI) during exposure to two emotion processing tasks. Overall both tests evoked much more extensive and intense cerebral activations in men than in women with schizophrenia. The pattern of obtained results differs significantly from what has been observed in the general population, thus giving support for the recent suggestion of “masculinization” of females and “feminization” of males with schizophrenia. More thorough investigation of a larger number of patients and healthy participants is currently on its way to substantiate this hypothesis.Recientemente los estudios neuroanatómicos han sugerido una inversión del dimorfismo sexual normal en las personas esquizofrénicas, en varias estructuras límbicas y corticolímbicas implicadas en el funcionamiento emocional. Estimulados por estos estudios, analizamos los datos provenientes de quince hombres y diez mujeres diagnosticados con esquizofrenia, que habían sido evaluados por medio de imágenes de resonancia magnética funcional (IRMf) durante la exposición a dos tareas emocionales. En general, los dos intentos evocaron activaciones cerebrales mucho más extensas y más intensas en los hombres que en las mujeres. La muestra de los resultados obtenidos difiere de manera significativa de lo que se había observado en la población general. Estos resultados aportan apoyo a la sugerencia de una “masculinización” de las mujeres y una “feminización” de los hombres diagnosticados con esquizofrenia. Actualmente se está realizando una investigación de un mayor número de pacientes y personas de control para confirmar esta hipótesis.Recentemente, estudos neuroanatômicos sugeriram uma inversão da deformidade sexual normal nas pessoas esquizofrênicas, em várias estruturas límbicas e corticolímbicas, implicadas no funcionamento emocional. Estimulados por estes estudos, analisamos dados provenientes de quinze homens e dez mulheres, com diagnóstico de esquizofrenia, que tinham sido medidos por Imagem em Ressonância Magnética Funcional (IRMf) durante a exposição a duas tarefas emocionais. De maneira geral, os dois testes evocaram ativações cerebrais muito mais vastas e muito mais intensas nos homens que nas mulheres. A amostragem dos resultados obtidos difere de maneira significativa do que tinha sido observado na população geral. Estes resultados apóiam a hipótese de uma “masculinização” das mulheres e de uma “feminização” dos homens que possuem um diagnóstico de esquizofrenia. Uma pesquisa junto a um maior número de pacientes e de sujeitos controlados está atualmente sendo realizada para confirmar esta hipótese

An fMRI investigation of trait and state markers in schizophrenia

Several contemporary theories of schizophrenia have implicated different neural networks in the pathophysiology of this disorder, including fronto-temporal circuitry, fronto-thalamo-cerebellar network, as well as cingulate gyrus with interconnected structures. The present thesis was designed to elucidate the precise nature of cerebral dysfunction and determine which parts of the distorted circuitry represent state and which are trait markers of schizophrenia. In order to achieve our goal we performed three experiments using functional magnetic resonance imaging (fMRI) and an "N-back" working memory task. In the Experiment 1 we explored the pattern of cerebral activity in healthy volunteers during performance of the "N-back" task. We observed significant activations and deactivations in a widespread network of areas we were interested in, including prefrontal cortex, thalamus, cerebellum, temporal cortex, as well as anterior and posterior cingulate. These results confirmed that the "N-back" task was well suited to examine cerebral functional anomalies in schizophrenia. In the Experiment 2 we investigated integrity of three circuits implicated in schizophrenia, in clinically stable patience and matched controls. The results revealed that patients exhibited decreased activity in the left dorsolateral prefrontal cortex (DLPFC) and the right cerebellum, increased activity in the left cerebellum, and failure to suppress cingulate gyrus and right superior temporal gyrus, as compared with healthy participants during performance of the "N-back" task. In the Experiment 3 we examined first-episode schizophrenic patients in two different stages of their illness and compared their data with control participants who were also scanned on two occasions, six to eight weeks apart. The results disclosed significant underactivation of the left DLPFC, left thalamus, and right cerebellum in patients relative to controls during both scanning sessions, whereas the function of the right DLPFC, right thalamus, left cerebellum, and posterior cingulate normalized over time with remission of psychotic state. Overall, the present investigation provided evidence that underactivation of the left DLPFC and right cerebellum, represents a stable trait marker of schizophrenia, whereas disturbances of the right DLPFC, left cerebellum, thalamus, and cingulate gyrus are state-related.Medicine, Faculty ofGraduat

Existe-t-il des différences entre les hommes et les femmes en ce qui concerne les problèmes de toxicomanie ?

La consommation et la dépendance aux drogues furent longtemps considérées comme un problème typiquement masculin. Néanmoins, bien que l’abus et la dépendance à l’alcool, au cannabis et à la nicotine soient encore plus répandus chez les hommes, les différences de genre en ce qui concerne les stimulants et les opiacés ont largement disparu. Il semblerait également que les motivations pour commencer à consommer, l’escalade vers la dépendance et les taux de cessation diffèrent chez les hommes et les femmes. Les raisons qui expliquent ces différences sont multiples et complexes. Nous allons examiner ici les données des études épidémiologiques et cliniques concernant la consommation de diverses drogues chez des hommes et chez des femmes en contexte des facteurs socioculturels, psychologiques et neurobiologiques.Drug use and drug addiction have been traditionally considered to be a male problem, however the gender gap has been decreasing over the past few decades. Thus, while the prevalence of alcohol, cannabis and nicotine dependence is still overall greater among men than among women, sex/gender differences in the abuse of stimulants and opiates seem to have disappeared. Moreover, women appear to be more prone to develop drug dependence, suffer more severe physical and psychological consequences of drug abuse, and have more difficulties quitting the habit. Numerous psychological, socio-cultural and biological factors have been implicated in these changing statistics. For example, while a large proportion of men initiate drug use to induce feelings of elation, energy or focus, women frequently start taking drugs to alleviate pre-existing mental health problems, including high levels of stress, feelings of alienation, depression, anxiety, or post-traumatic stress disorder. This maladaptive self-medication strategy often results in a faster transition to a habitual drug use and eventually a more severe dependence. In addition, the socio-cultural norms (particularly in the Western society) have changed dramatically over the past few decades. Thus, while there is still a more severe stigma and prejudice against women who use drugs (especially if they are pregnant of have children), overall there is much greater acceptance of women’s drug use than it was several decades ago. Moreover, women have much greater access to various drugs of abuse than they used to have. Finally, over the past couple of decades new research started emerging pointing to some neurobiological factors that could also contribute to sex differences in drug addiction. Thus, there is now evidence that dopamine system, which for decades has been strongly implicated in drug reinforcement, is sexually dimorphic. The number of dopaminergic neurons, the density of the dopaminergic terminals, as well as responsiveness of the dopaminergic system to drugs of abuse, has been shown to differ between males and females and it has been shown to be modulated by sex steroid hormones, especially estrogen. For example, female rats exhibit greater motivation to self-administer cocaine than male rats and their motivation is the highest during elevated levels of estrogen. All these psychological, socio-cultural and biological factors that contribute to sex/gender difference in drug use and drug dependence, should be considered while evaluating and treating individuals with drug addiction problem

Preexposure sensitizes rats to the rewarding properties of amphetamine as measured by a progressive ratio paradigm

Two groups of male Long-Evans rats were compared to determine whether preexposure to amphetamine would enhance the motivation to self-administer the drug under a progressive ratio schedule of reinforcement. In the first phase of the experiment each animal received a single injection of either amphetamine or saline on alternate days for a total of ten injections. Following a 21 day withdrawal period, behavioral sensitization was confirmed by a significant increase in amphetamine-induced stereotypy in the amphetamine-pretreated group, relative to the saline-pretreated group. In the second phase of the study all rats were implanted with chronic jugular catheters and trained to'self-administer amphetamine under a fixed-ratio schedule of reinforcement. The progressive ratio paradigm was then imposed for seven days; amphetamine-pretreated rats attained significantly higher breaking points than saline-pretreated animals. These data indicate that preexposure to psychoactive agents may enhance the motivation of drug self-administration, suggesting augmentation in drug addiction liability.Arts, Faculty ofPsychology, Department ofGraduat

Differentiating men and women with schizophrenia according to their cognitive profiles

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Computerized assessment of cognition in schizophrenia: promises and pitfalls of CANTAB.

OBJECTIVE: Over the last decade, the Cambridge Neuropsychological Test Automated Battery (CANTAB), which comprises visuo-spatial tasks, has been utilized in cognitive studies of schizophrenia. A clear approach concerning the usage of CANTAB for the appraisal of neurocognitive dysfunction in schizophrenia is currently lacking. METHOD: In this paper, we have first reviewed the overall applications of CANTAB and then evaluated methodological strengths and weaknesses of CANTAB as a neurocognitive battery for schizophrenia. We carried out a systematic search and assessment of studies where CANTAB was utilized to measure cognitive function in schizophrenia. We have also attempted to quantify the available data and perform a meta-analysis, but this approach turned out to be still premature. RESULTS: CANTAB has enabled researchers to highlight significant deficits affecting broad cognitive domains in schizophrenia, such as working memory, decision-making, attention, executive functions and visual memory. So far, the most consistent deficit observed with CANTAB testing has been attentional set-shifting, suggestive of fronto-striatal dysfunctions. In addition, preliminary evidence points towards the potential use of CANTAB to identify cognitive predictors of psychosocial functioning, to describe the relationships between symptoms and cognition, and to measure the impact of pharmacological agents on cognitive functioning. CONCLUSION: CANTAB has been used successfully to highlight the range of visuo-spatial cognitive deficits in schizophrenia, producing similar results to those obtained with some traditional neuropsychological tests. Further studies validating the use of CANTAB following the standard set by Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) are warranted

Mémoire émotionnelle et activités électrocorticales en schizophrénie

Contexte L’altération des fonctions émotionnelles ainsi que de la mémoire des personnes atteintes de schizophrénie est connue depuis plus d’un siècle. Toutefois, les structures cérébrales touchées ainsi que les stades de traitement affectés restent encore mal compris.Objectif Approfondir de quelles façons la valence et l’activation émotionnelle affectent la mémoire épisodique et l’activité cérébrale associée chez des patientes atteintes de schizophrénie.Hypothèse L’activité des régions frontales associées à certains types de stimuli émotifs sera généralement affectée dans la population clinique, et ce, en réponse aux stimuli à fortes activations émotionnelles.Participantes Seize patientes atteintes de schizophrénie dans une phase stable de leur maladie furent appariées à 17 participantes contrôles sur la base de l’âge, de la dominance manuelle et du statut socio-économique.Instrument et mesures L’EEG a été enregistré à partir de 60 électrodes fixées dans un casque en lycra élastique. Ces signaux ont été moyennés pour obtenir les composantes N200, P300, ainsi que la LPC afin de cibler les processus mnésiques et émotionnels.Résultats Pour la N200 et la P300 frontale, la magnitude de l’effet de mémoire observé chez les patientes schizophrènes est augmentée significativement dans l’hémisphère frontal droit en réponse aux stimuli à valences déplaisantes, alors que l’augmentation de cet effet s’effectue dans les deux hémisphères chez les participantes contrôles.Conclusion Une altération électrocorticale précoce reflétant la familiarité et la mémoire aux stimuli déplaisants est présente chez les patientes, alors que les processus tardifs de récollection consciente (LPC pariétale) ne seraient pas atteints.Context Abnormal emotion processing is frequent in schizophrenia and affects social and functional outcome. Past event-related potential (ERP) research investigating processing of affective stimuli in schizophrenia was done mainly with facial expressions and revealed impaired facial emotion recognition in patients relative to control subjects. Experimentations involving fMRI with this group of patients, showed alteration of limbic and frontal regions in response to emotional unpleasant images, compared to neutral stimuli during a memory task. Other studies have also noted an increase in brain activity when the activation of the stimuli was high compared to low arousal stimuli. This may indicate a different sensitivity threshold to emotional arousal and emotional valence involving frontal pathways in these patients. But very few studies attempted to separate the contributions of emotional valence and arousal within an episodic memory protocol with ERP, in that population.Goal The aim of the current research is to investigate brain electro-cortical activity in schizophrenia in response to emotional images during an episodic memory task.Method ERP components were analyzed in 16 schizophrenic and 17 control participants matched for age, sex and intelligence. ERPs were obtained from 56 EEG electrodes. The tasks consisted in a classical episodic memory task that presented 100 repeated old and 100 new photographic images divided into four categories (unpleasant-high arousal, unpleasant-low arousal, pleasant-high arousal and pleasant-low arousal) selected from the International Affective Picture System. The N200, P300 and late positive component (LPC) mean amplitude, were analyzed using repeated-measure analyses of variance (MANOVA).Results Patients with schizophrenia and control subjects gave comparable subjective evaluations of arousal and valence. However, the frontal N200 and the P300 both showed an interaction of the group x memory x valence x hemisphere (F [1.32]=8.36; p <.01). Thus, this complex interaction denotes an increase of the episodic memory effect in the right hemisphere in response to unpleasant stimuli, with schizophrenic patients. With respect to the control group, there is also an increase of this memory effect in the right hemisphere, but in response to pleasant stimuli. The schizophrenic patients presented a smaller LPC memory effect, especially at the frontal region. More specifically, the frontal LPC was reduced, and the clinical group was less reactive to the emotional arousal content, compared to the control group.Discussion Altogether, our results revealed that while the subjective evaluation of emotional pictures is equivalent across groups, cerebral differences are present in schizophrenic patients during emotional recognition. N200 and P300 results in the frontal region suggest impaired selective attention and episodic memory to unpleasant stimuli in patients, while later processes related to conscious recollection (parietal LPC) are not affected with patients affected with schizophrenia.Conclusion This finding provides further support for the notion of a possible discrepancy between the subjective experience and the physiological expression of emotions in schizophrenia patients. Those results could open the door to new clinical research investigations in psychiatry, particularly in the comprehension of a relationship between frontal cortex vulnerability and episodic memory often present in psychosis

Neural Circuitry of Impulsivity in a Cigarette Craving Paradigm

Impulsivity has been shown to play a pivotal role in the onset, pattern of consumption, relapse and, most notably, craving of illicit and licit drugs such as cigarette smoking. The goal of this study was to examine the neurobiological influence of trait impulsivity during cue-induced cigarette craving. Thirty-one chronic smokers passively viewed appetitive smoking-related and neutral images while being scanned and reported their feelings of craving. They completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. We conducted functional connectivity analyses using the psycho-physiological interaction method. During the processing of smoking stimuli, participants presented increased activations in the cingulate and prefrontal cortices. We observed a significant positive relationship between impulsivity scores and reported craving. A negative correlation was observed between the impulsivity score and activity in the posterior cingulate cortex (PCC). The insula, dorsal anterior cingulate cortex (dACC) as well as the dorsolateral prefrontal cortex (DLPFC) presented a negative connectivity with the PCC. Consistent with the view that the PCC is related to the ability to resist cigarette craving, our results suggest that high impulsive smokers have greater difficulty in controlling their cravings, and that this weakness may be mediated by lower PCC activity. Moreover, we argue that the less PCC activity, the greater the probability of a stronger emotional, physiological, and biased attentional response to smoking cues mediated by insula, dACC, and DLPFC activity. This is the first study on this topic, and so, results will need to be replicated in both licit and illicit drug abusers. Our findings also highlight a need for more emphasis on the PCC in drug addiction research, as it is one of the most consistently activated regions in functional magnetic resonance imaging studies examining the neural correlates of cue-induced alcohol, drug, and tobacco cravings

Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with Attention-Deficit Hyperactivity Disorder: A Systematic Review

Mindfulness-based interventions (MBIs) are becoming increasingly popular as treatments for physical and psychological problems. Recently, several studies have suggested that MBIs may also be effective in reducing symptoms of attention-deficit hyperactivity disorder (ADHD). Most studies have examined the effectiveness in children, but there are now a sufficient number of individual treatment trials to consider a systematic review in adults. Majority of existing systematic reviews and meta-analyses only consider ADHD symptoms as an outcome, and most of them do not fully report potential biases of included studies, thus limiting considerably their conclusions. This is an important facet because some studies could be found ineligible to be included in future analysis due to their low quality. In this systematic review, we followed the PRISMA/PICO criteria and we thoroughly assessed the risks of bias for each of the selected studies according to Cochrane guidelines. We searched the available literature concerning MBIs in adult participants with ADHD using PsycINFO, PubMed, Scopus, and ERIC databases. In total, 13 studies conducted with 753 adults (mean age of 35.1 years) were identified as eligible. Potential moderators such as participants’ age, ADHD subtypes, medication status, comorbidity, intervention length, mindfulness techniques, homework amount, and training of therapists were carefully described. Aside from measuring the symptoms of ADHD, outcome measures were categorized into executive/cognitive functioning, emotional disturbances, quality of life, mindfulness, and grade point average at school. According to presented descriptive results, all the studies (100%) showed improvement of ADHD symptoms. In addition, mindfulness meditation training improves some aspects of executive function and emotion dysregulation. Although these are promising findings to support treatment efficacy of MBIs for ADHD, various biases such as absence of randomization and lack of a control group may affect the actual clinical value and implications of the studies. Moreover, the relatively low quality of selection and performance criteria in several studies, as well as relatively high attrition bias across studies, call for caution before considering conducting further analysis