Réflexion psychodynamique : À propos d’une structure de personnalité toxicomaniaque spécifique à l’alcool et aux drogues dures

La surconsommation de substances psychotropes représente un problème majeur des sociétés contemporaines. Aux États-Unis, 14,1 % de la population âgée entre 15 et 54 ans a vécu des problèmes de dépendance à l'alcool au cours de la vie alors que 7,5 % des gens ont connu une dépendance à vie aux autres drogues (cannabis, cocaïne, stimulants, etc.). Plusieurs études rapportent que la consommation excessive d'alcool, concomitante ou non avec l'utilisation de drogues illégales, est associée à des conditions sociales favorisant le développement de la détresse psychologique et de l'isolement. Bien qu'il existe plusieurs recherches traitant des différences entre les traits de personnalité alcooliques et ceux des consommateurs de drogues dures, peu d'auteurs se sont penchés sur la possibilité de mettre en évidence une spécificité entre l'aménagement structurel de l'alcoolique et celui du dépendant aux autres drogues d'un point de vue psychodynamique. Cette recension des écrits, à caractère exploratoire, présente d'abord les travaux effectués afin d'identifier les traits de personnalités communs ou distincts à ces formes de toxicomanie. La réflexion porte ensuite sur les écrits psychodynamiques qui s'intéressent à la possibilité d'une organisation structurelle propre à la toxicomanie. Enfin, les auteurs proposent quelques réflexions permettant de postuler l'existence d'un aménagement structurel spécifique à ces deux formes de toxicomanie.The overconsumption of psychotropic substances is a major problem for contemporary societies. In the USA, 14,1% of the population between the age 15 and 54 have experienced addiction problems to alcohol during their lives while as 7,5% are addicted for life to other drugs (cannabis, cocaine, stimulants, etc). Many studies report that excessive consumption of alcohol, with or without illegal drug use, is associated to social conditions favoring the development of psychological distress and isolation. Although there are many studies on the differences between personality traits of alcoholics and drug users, few authors have examined the possibility to bring to the fore a specificity between the personality structures of the alcoholic and the drug user from a psychodynamic approach. This exploratory review of literature, first presents studies already conducted in order to identify common or distinct personality features for these types of addiction. This article then reviews psychodynamic writings examining the possibility of a structural organization that is specific to addiction. Finally, the authors propose a few thoughts allowing to postulate on the existence of a structural organization specific to these two types of addiction.El consumo abusivo de sustancias sicodélicas représenta un problema major de las sociedades contemporâneas. En los Estados Unidos, 14.1% de la poblaciôn entre 15 y 54 anos han vivido a Io largo de la vida problemas de dependencia al alcohol mientras que 7.5% de las personas han conocido una dependencia a vida de otras drogas (marihuana, cocaina, estimulantes, etc.). Varios estudios informan que el consumo excesivo del alcohol, acompanando o no de la utilizaciôn de drogas ilegales, esta asociado a condiciones sociales que favorecen el desarrollo de la angustia sicolôgica y del aislamiento. Aunque existen varias investigaciones que tratan de las diferencias entre los rasgos de la personalidad alcoholica y el de los consumidores de drogas duras, pocos autores se han preocupado de la posibilidad de evidenciar una especificidad entre un arreglo estructural del alcoholico y del adicto a las otras drogas, desde un punto de vista sicodinâmico. Esta resenciôn exploratoria de escritos, présenta primero los trabajos efectuados con el fin de identificar los rasgos de la personalidad comunes o distintos a estas formas de toxicomania. En seguida la reflexion es conducida a nivel de los escritos sicodinâmicos que se interesan en la posibilidad de una organization estructural propia a la toxicomania. En fin, este articulo propone algunas reflexiones que permiten postular la existencia de un arreglo estructural especifico a estas dos formas de toxicomania

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer’s disease: a behavioral and neuroimaging study

The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer’s disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions

The role of the left anterior temporal lobe for unpredictable and complex mappings in word reading

The anterior temporal lobes (ATLs) have been consistently associated with semantic processing which, in turn, has a key role in reading aloud single words. This study aimed to investigate (1) the reading abilities in patients with the semantic variant of primary progressive aphasia (svPPA), and (2) the relationship between gray matter (GM) volume of the left ATL and word reading performance using voxel-based morphometry (VBM). Three groups of participants (svPPA, Alzheimer’s Disease, AD and healthy elderly adults) performed a reading task with exception words, regular words and pseudowords, along with a structural magnetic resonance imaging scan. For exception words, the svPPA group had a lower accuracy and a greater number of regularization errors as compared to the control groups of healthy participants and AD patients. Similarly, for regular words, svPPA patients had a lower accuracy in comparison with AD patients, and a greater number of errors related to complex orthography-to-phonology mappings (OPM) in comparison to both control groups. VBM analyses revealed that GM volume of the left ATL was associated with the number of regularization errors. Also, GM volume of the left lateral ATL was associated with the number of errors with complex OPM during regular word reading. Our results suggest that the left ATL might play a role in the reading of exception words, in accordance with its role in semantic processing. Results further support the involvement of the left lateral ATL in combinatorial processes, including the integration of semantic and phonological information, for both exception and regular words

Evaluation of intensive versus standard blood pressure reduction and association with cognitive decline and dementia : a systematic review and metaAnalysis

Importance: Optimal blood pressure (BP) targets for the prevention of cognitive impairment remain uncertain. Objective: To explore the association of intensive (i.e. lower than usual) BP reduction compared to guidelines on the incidence of cognitive decline and dementia in adults with hypertension. Data Sources and Study Selection: We conducted a systematic review and meta-analysis of randomized controlled trials that evaluated the association of intensive systolic BP lowering on cognitive outcomes by searching MEDLINE, Embase, CENTRAL, Web of Science, CINAHL, PsycINFO, ICTRP and ClinicalTrials.gov for data up to October 27, 2020. Data Extraction and Synthesis: Data screening and extraction were performed independently by two reviewers based on PRISMA guidelines. The risk of bias was assessed using the Cochrane risk-of-bias 2 tool. We used random-effects models using the inverse variance method for our pooled analyses. We evaluated the presence of potential heterogeneity with the I2 index. Main Outcomes and Measures: Our primary outcome was cognitive decline. Secondary outcomes included the incidence of dementia, mild cognitive impairment (MCI), cerebrovascular events, serious adverse events, and all-cause mortality. Results: From 7,755 citations, we identified sixteen publications from five trials (17,396 participants, mean age 65.7 years, 60.5% males) and two additional ongoing trials. All five trials included in quantitative analyses were considered at unclear to high risk of bias. The mean followup duration was 3.3 years (range 2.0 to 4.7 years). Intensive BP reduction was not significantly associated with global cognitive performance (SMD 0.01, 95% CI -0.04 to 0.06, I2 = 0%, four trials, 5,246 patients), incidence of dementia (RR 1.09, 95% CI 0.32 to 3.67, I2 = 27%, two trials, 9,444 patients) or incidence of MCI (RR 0.91, 95% CI 0.73 to 1.14, I2 = 74%, two trials, 10,774 patients) when compared to standard treatment. However, we found a reduction of cerebrovascular events in the intensive arm (RR 0.79, 95% CI 0.67-0.93, I2 = 0%, five trials, 17,396 patients) without an increased risk of serious adverse events or mortality. Conclusions and Relevance: We did not detect a significant association between BP reduction and lower risk of cognitive decline, dementia or MCI. The certainty of this evidence is low due to the limited sample size, the risk of bias of included trials and the observed statistical heterogeneity. Hence, current available evidence does not justify the use of lower BP targets for the prevention of cognitive decline and dementi

18 F-MK-6240 tau-PET in genetic frontotemporal dementia

Tau is one of several proteins associated with frontotemporal dementia. While knowing which protein is causing a patient\u27s disease is crucial, no biomarker currently exists for identifying tau in vivo in frontotemporal dementia. The objective of this study was to investigate the potential for the promising 18F-MK-6240 PET tracer to bind to tau in vivo in genetic frontotemporal dementia. We enrolled subjects with genetic frontotemporal dementia, who constitute an ideal population for testing because their pathology is already known based on their mutation. Ten participants (three with symptomatic P301L and R406W MAPT mutations expected to show tau binding, three with presymptomatic MAPT mutations and four with non-tau mutations who acted as disease controls) underwent clinical characterization, tau-PET scanning with 18F-MK-6240, amyloid-PET imaging with 18F-NAV-4694 to rule out confounding Alzheimer\u27s pathology, and high-resolution structural MRI. Tau-PET scans of all three symptomatic MAPT carriers demonstrated at least mild 18F-MK-6240 binding in expected regions, with particularly strong binding in a subject with an R406W MAPT mutation (known to be associated with Alzheimer\u27s like neurofibrillary tangles). Two asymptomatic MAPT carriers estimated to be 5 years from disease onset both showed modest 18F-MK-6240 binding, while one ∼30 years from disease onset did not exhibit any binding. Additionally, four individuals with symptomatic frontotemporal dementia caused by a non-tau mutation were scanned (two C9orf72; one GRN; one VCP): 18F-MK-6240 scans were negative for three subjects, while one advanced C9orf72 case showed minimal regionally non-specific binding. All 10 amyloid-PET scans were negative. Furthermore, a general linear model contrasting genetic frontotemporal dementia subjects to a set of 83 age-matched controls showed significant binding only in the MAPT carriers in selected frontal, temporal and subcortical regions. In summary, our findings demonstrate mild but significant binding of MK-6240 in amyloid-negative P301L and R406W MAPT mutation subjects, with higher standardized uptake value ratio in the R406W mutation associated with the presence of NFTs, and little non-specific binding. These results highlight that a positive 18F-MK-6240 tau-PET does not necessarily imply a diagnosis of Alzheimer\u27s disease and point towards a potential use for 18F-MK-6240 as a biomarker in certain tauopathies beyond Alzheimer\u27s, although further patient recruitment and autopsy studies will be necessary to determine clinical applicability

Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia.

The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically.The Italian Ministry of Health The Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant [grant number CoEN01

Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study.

OBJECTIVE: To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD. METHODS: GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer's disease (AD) and 10 healthy controls (HCs) of similar age. RESULTS: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98). CONCLUSIONS: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD