Schizophrénie et toxicomanie : l’héritage du psychiatre Jean-Yves Roy

Cher Jean-Yves, le 27 avril 2004, tu nous as quitté sur la pointe des pieds, laissant inachevés des projets de recherche portant sur la comorbidité schizophrénie — toxicomanie, que nous avons eu l’occasion de compléter au cours des dernières années au Centre de recherche Fernand-Seguin. Ce sont ces développements que nous souhaitons ici te raconter. Nous te présentons d’abord une série de travaux qui évaluent la validité de l’hypothèse de l’automédication, impliquant diverses techniques scientifiques (méta-analyse, imagerie cérébrale et neuropsychologie). Les résultats de ces travaux suggèrent fortement que les patients souffrant à la fois de schizophrénie et de toxicomanie ont moins de symptômes négatifs et de déficits cognitifs que les patients non toxicomanes. Ils présentent toutefois davantage de symptômes extrapyramidaux. En particulier, les résultats montrent que les patients avec un double diagnostic ont moins d’anhédonie, ce qui place la notion de plaisir au coeur de l’enjeu de la comorbidité, comme tu l’anticipais justement. Nous présentons ensuite les résultats préliminaires d’une étude ouverte qui suggère un potentiel effet bénéfique de la quétiapine chez les patients schizophrènes et toxicomanes, une étude qui nous également permis, comme tu l’espérais, de mettre en lumière des relations intrigantes entre les cannabinoïdes endogènes, les cytokines, la schizophrénie et la toxicomanie. Le caractère prometteur de ces résultats a fait en sorte que nous venons d’obtenir un financement où nous pourrons évaluer, dans les mêmes conditions et selon les mêmes paramètres, des patients schizophrènes non toxicomanes et des patients toxicomanes qui ne souffrent pas d’un trouble psychotique.On April 27th 2004, Dr Jean-Yves Roy passed away, leaving unachieved research projects on the schizophrenia — substance abuse comorbidity, which we were able to complete over the last few years at the Fernand-Seguin Research Center. It is these developments that we summarize in the current review of literature. First, we present a series of studies evaluating the self-medication hypothesis, using diverse scientific techniques (meta-analysis, brain imaging and neuropsychology). The results of these studies strongly suggest that patients with schizophrenia and substance abuse have less negative deficits and less cognitive deficits, compared to non-abusing patients. However, these dual diagnosis patients suffer from more extrapyramidal symptoms. In particular, our results demonstrate that dual diagnosis patients show less anhedonia, which emphasizes the key role of pleasure in comorbid patients, as anticipated by Dr Roy. We also present preliminary results form an open-label study suggesting a potential beneficial effect of quetiapine among patients with schizophrenia and substance abuse. This study also allowed to highlight intriguing relationships between endogenous cannabinoids, cytokines, schizophrenia and substance abuse. Being promising, these results have paved the way to a broader study evaluating, in the same conditions and using the same parameters, non-abusing patients with schizophrenia and non-psychosis substance abusers.Estimado Jean-Yves, el 27 de abril de 2004 te fuiste de puntitas, dejaste sin terminar los proyectos de investigación sobre la comorbilidad esquizofrenia – toxicomanía que pudimos completar en el curso del los últimos años en el Centro de Investigación Fernand-Seguin. Estos desarrollos son lo que deseamos contarte. Te presentamos primero una serie de trabajos que evalúan la validez de la hipótesis de automedicación, que implica diversas técnicas científicas (metanálisis, imágenes cerebrales y neuropsicología). Los resultados de estos trabajos sugieren fuertemente que los pacientes que sufren a la vez de esquizofrenia y toxicomanía tienen menos síntomas negativos y déficits cognitivos que los pacientes que no son toxicómanos. Sin embargo, presentan más síntomas extrapiramidales. En particular, los resultados muestran que los pacientes con un diagnóstico doble tienen menos anhedonia, lo cual coloca la noción de placer en el corazón de las cuestiones de la comorbidad justamente como lo anticipabas. Enseguida presentamos los resultados preliminares de un estudio abierto que sugiere un potencial efecto benéfico de la quetiapina en los pacientes esquizofrénicos y toxicómanos, un estudio que también nos ha permitido, como lo esperabas, resaltar las relaciones intrigantes entre los canabinoides endógenos, los citoquinos, la esquizofrenia y la toxicomanía. El carácter prometedor de estos resultados hace que hayamos obtenido un financiamiento con el que podremos evaluar, en las mismas condiciones y según los mismos parámetros, a los pacientes esquizofrénicos no toxicómanos y los pacientes toxicómanos que no sufren de un trastorno psicótico.Caro Jean-Yves, dia 28 de abril de 2004, você nos abandonou de mansinho, deixando inacabados os projetos de pesquisa que tratam sobre a comorbidade esquizofrenia-toxicomania, que tivemos a ocasião de concluir durante os últimos anos no Centro de pesquisa Fernand-Seguin. São estes desenvolvimentos que desejamos contar-lhe aqui. Queremos lhe apresentar primeiramente uma série de trabalhos que avaliam a validade da hipótese de automedicação, implicando várias técnicas científicas (metanálise, imagem cerebral e neuropsicológica). Os resultados destes trabalhos sugerem fortemente que os pacientes, que sofrem ao mesmo tempo de esquizofrenia e de toxicomania, têm menos sintomas negativos e déficits cognitivos que os pacientes não toxicômanos. Eles apresentam, entretanto, mais sintomas extrapiramidais. Principalmente, os resultados demonstram que os pacientes com um duplo diagnóstico têm menos anedonia, o que coloca a noção de prazer no centro da questão da comorbidade, justamente como você suspeitava. Apresentamos, em seguida os resultados preliminares de um estudo aberto que sugere um potencial efeito benéfico da quetiapina nos pacientes esquizofrênicos e toxicômanos, um estudo que também nos permitiu, como você esperava, esclarecer as relações intrigantes entre os canabinóides endógenos, as citocinas, a esquizofrenia e a toxicomania. O caráter promissor destes resultados fez com que obtivéssemos um financiamento que nos permitirá avaliar, nas mesmas condições e segundo os mesmos parâmetros, pacientes esquizofrênicos não toxicômanos e pacientes toxicômanos que não sofrem de um transtorno psicótico

L'incompatibilité de deux visions darwiniennes de l'esprit humain : la psychologie évolutionniste et le "darwinisme neuronal"

Mémoire numérisé par la Direction des bibliothèques de l’Université de MontréalAlors que l'on assiste, depuis l'aube des années 1990, à un regain de popularité de la pensée de Charles Darwin dans l'étude de l'être humain, on constate que les deux principales écoles qui sont responsables de cette réhabilitation, la psychologie évolutionniste et le "darwinisme neuronal, défendent des thèses nettement incompatibles au sujet de la nature de la psyché humaine. L'esprit se compose-t-il exclusivement de modules ? Se développe-t-il sous l'emprise tyrannique des gènes ? Si tel est le cas, est-il possible de réduire la psychologie à la biologie évolutionniste ? À ces trois questions, la psychologie évolutionniste, qui découle historiquement de la sociobiologie, répond par l'affirmative, alors que le "darwinisme neuronal", développé par les neurologues Jean-Pierre Changeux et Gerald Edelman, répond par la négative. Après avoir exposé, à l'aide de la littérature philosophique des dernières années, les failles épistémologiques et ontologiques de la psychologie évolutionniste, le présent projet procède à une analyse philosophique du "darwinisme neuronal". Ce que ce second examen permet de suggérer, sans le démontrer hors de tout doute, c'est que l’esprit n'est pas massivement modulaire, que son développement est épigénétique, et par conséquent, que la psychologie préserve son autonomie épistémique par rapport à la biologie évolutionniste

Temporal Summation of Pain Is Not Amplified in a Large Proportion of Fibromyalgia Patients

Background. Recently, it has been proposed that fibromyalgia (FM), a chronic widespread pain syndrome, results from overactive endogenous excitatory pain mechanisms. Experimental studies using temporal summation paradigms have confirmed this hypothesis but have included small samples of patients, prompting our group to perform a large-scale study. Methods. Seventy-two female FM patients and 39 healthy females participated in the study. The temporal summation test consisted of a 2-minute continuous and constant heat pulse administered with a thermode on the participants' left forearm. Experimental temperature was set at a value individually predetermined to induce a 50/100 pain rating. Results. Relative to controls, FM patients had lower thermal pain thresholds and lower temporal summation of pain. However, 37 FM patients required experimental temperatures lower than the minimal temperature used in controls (45°C). Nevertheless, temporal summation was not increased in the other FM subgroup, relative to controls, despite equivalent experimental temperatures. Discussion. Our results suggest that temporal summation of pain is normal, rather than increased, in a large proportion of FM patients. Future studies on temporal summation in FM will need to be careful since some FM patients require abnormally low experimental temperatures that may confound results and make necessary to separate patients into subgroups

Améliorer les symptômes et le tabagisme chez les personnes souffrant de schizophrénie : un manque d’effet synergique du médicament antipsychotique

Contexte : Le tabagisme est élevé chez les personnes souffrant de schizophrénie ; certains patients réclament une aide au niveau de la médication qu’ils reçoivent afin de cesser de fumer. Objectif : Parmi les traitements pharmacologiques de la schizophrénie, la clozapine peut réduire la consommation de cigarettes. Les effets de la quétiapine, un autre antipsychotique atypique partageant plusieurs propriétés structurales et pharmacologiques avec la clozapine, ont été examinés chez un groupe de fumeurs atteints de schizophrénie dans une étude exploratoire. Méthode : Vingt-et-un individus fumeurs avec un diagnostic de schizophrénie, de trouble schizo-affectif ou de trouble schizophréniforme et recevant de la quétiapine ont été évalués à l’aide du questionnaire de Fagerström pour la dépendance à la nicotine. Ils ont de plus subi des analyses de monoxyde de carbone sanguin. Résultats : Le profil tabagique des sujets n’a pas été modifié significativement par l’administration de la quétiapine, malgré une amélioration de la symptomatologie psychiatrique. Conclusion : La quétiapine ne semble pas avoir d’effet significatif sur la consommation de cigarettes chez les fumeurs souffrant de schizophrénie.Context: Tobacco use is high among people suffering from schizophrenia ; certain patients demand help at the medication level they receive in order to stop smoking. Objective: Among the pharmacological treatment of schizophrenia, clozapine can reduce tobacco use. The effects of quetiapine, another atypical antipsychotic medication sharing several structural and pharmacological properties with clozapine, have been examined in a group of smokers with schizophrenia in an exploratory study. Method: Twenty-one smoking individuals with a diagnosis of schizophrenia, schizo-affective disorder or schizophreniform disorder and receiving quetiapine have been evaluated with the help of a questionnaire elaborated by Fagerström for nicotine addiction. They also were submitted to carbon monoxide blood analyses. Results: The tobacco profile of subjects was not modified significantly by the administration of quetiapine, despite an improvement of the psychiatric symptomatology. Conclusion: Quetiapine does not appear to have a significant effect on tobacco use in smokers suffering from schizophrenia.Contexto: El tabaquismo es elevado en las personas que sufren de esquizofrenia; algunos pacientes requieren ayuda a nivel de la medicación que reciben a fin de dejar de fumar. Objetivo: Entre los tratamientos farmacológicos de la esquizofrenia, la clozapina puede reducir el consumo de cigarrillos. Los efectos de la quetiapina, otro antipsicótico atípico que comparte varias propiedades estructurales y farmacológicas con la clozapina, han sido examinados en un estudio exploratorio de un grupo de fumadores que sufren de esquizofrenia. Método: Veintiún individuos fumadores diagnosticados con esquizofrenia, de trastorno esquizoafectivo o de trastorno esquizofreniforme, y que reciben quetiapina fueron evaluados con ayuda del cuestionario de Fagerström para la dependencia a la nicotina. Además se les realizaron análisis sanguíneos de monóxido de carbono. Resultados: la administración de quetiapina no modificó significativamente el perfil de tabaquismo de los pacientes, a pesar de la mejora de la sintomatología psiquiátrica. Conclusión: La quetiapina no parece tener efectos significativos en el consumo de cigarrillos en los fumadores que sufren de esquizofrenia.Contexto: O tabagismo é elevado nas pessoas que sofrem de esquizofrenia; alguns pacientes pedem a prescrição de remédios a fim de parar de fumar. Objetivo: Entre os tratamentos farmacológicos da esquizofrenia, a clozapina pode reduzir o consumo de cigarro. Os efeitos da quetiapina, um outro antipsicótico atípico que possui várias propriedades estruturais e farmacológicas semelhantes às da clozapina, foram examinados em um grupo de fumantes que sofrem de esquizofrenia em um estudo exploratório. Método: 21 indivíduos fumantes com um diagnóstico de esquizofrenia, transtorno esquizoafetivo ou de transtorno esquizofreniforme e que recebem quetiapina foram avaliados com a ajuda do questionário de Fageström para a dependência à nicotina. Além disto, eles passaram por análises de monóxido de carbono sangüíneo. Resultados: o perfil tabagístico das pessoas não foi modificado significativamente pela administração da quetiapina, apesar da melhoria da sintomatologia psiquiátrica. Conclusão: A quetiapina não parece ter efeito significativo no consumo de cigarros nos fumantes que sofrem de esquizofrenia

Measurement invariance of the Marijuana Motives Measure among men and women using Stop Cannabis App

Motives to use cannabis play a central role in the development and maintenance of problematic cannabis use and previous studies stressed sex-related differences on motives to use cannabis. However, motives cannot be validly compared in men and women without first establishing the measurement invariance across sex. Therefore, the aim of the study is to (1) examine for the first time the measurement and structural invariance of the Marijuana Motives Measure (MMM) across sex, and (2) to investigate the motives for cannabis use that best explain problematic use. 2951 (41.7% women) users of the "Stop cannabis" smartphone app of which 99.8% reported having used cannabis in the last three months completed an online MMM and ASSIST to assess the severity of their problematic cannabis use. Multigroup confirmatory factor analyses supported measurement invariance across sex, whereas structural invariance was not confirmed. Indeed, group comparisons indicated that women reported greater coping motives then men whereas men showed greater social motives than women. A multiple linear regression analysis showed that only coping and conformity motives were significantly associated with greater problematic cannabis use, whereas neither sex nor the sex by motives interactions were significantly related to problematic cannabis use. The MMM appears to function comparably across men and women. Therefore, sex-related comparisons on the questionnaire can be considered valid. Coping and conformity motives may play a central role part in the development of marijuana use problems which may hold implications for intervention development and public policy

Label-based meta-analysis of functional brain dysconnectivity across mood and psychotic disorders.

peer reviewed[en] BACKGROUND: Resting-state functional magnetic resonance imaging (rsfMRI) studies have revealed patterns of functional brain dysconnectivity in psychiatric disorders such as major depression disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). Although these disorders have been mostly studied in isolation, there is mounting evidence of shared neurobiological alterations across them. METHODS: To uncover the nature of the relatedness between these psychiatric disorders, we conducted an innovative meta-analysis of dysconnectivity findings reported separately in MDD, BD and SZ. Rather than relying on a classical voxel level coordinate-based approach, our procedure extracted relevant neuroanatomical labels from text data and examined findings at the whole brain network level. Data were drawn from 428 rsfMRI studies investigating MDD (158 studies, 7429 patients/7414 controls), BD (81 studies, 3330 patients/4096 patients) and/or SZ (223 studies, 11,168 patients/11,754 controls). Permutation testing revealed commonalities and differences in hypoconnectivity and hyperconnectivity patterns across disorders. RESULTS: Hypoconnectivity and hyperconnectivity patterns of higher-order cognitive (default-mode, fronto-parietal, cingulo-opercular) networks were similarly observed across the three disorders. By contrast, dysconnectivity of lower-order (somatomotor, visual, auditory) networks in some cases differed between disorders, notably dissociating SZ from BD and MDD. CONCLUSIONS: Findings suggest that functional brain dysconnectivity of higher-order cognitive networks is largely transdiagnostic in nature while that of lower-order networks may best discriminate between mood and psychotic disorders, thus emphasizing the relevance of motor and sensory networks to psychiatric neuroscience

Functional neuroimaging predictors of self-reported psychotic symptoms in adolescents

OBJECTIVE: This study aimed to investigate the neural correlates of psychotic-like experiences in youth on measures of inhibitory control, reward anticipation and emotion processing. A secondary aim was to test whether these neuro-functional correlates of risk were predictive of psychotic symptoms 2 years later. METHOD: Functional imaging response to three paradigms: the Stop-Signal, Monetary Incentive Delay, and Faces tasks was collected in youth at age 14, as part of the IMAGEN study. At baseline, youth from London and Dublin sites were assessed on psychotic-like experiences and those reporting significant experiences were compared with matched controls. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublin subsample (N=246) and the full sample (N=1196). RESULTS: Youth reporting psychotic-like experiences showed increased hippocampus/amygdala activity during neutral faces processing and reduced dorsolateral prefrontal activity during failed inhibition relative to controls. The most prominent region for classifying 16-year olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) included hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use. CONCLUSIONS: The results stress the importance of the limbic network’s increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youth