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

Education modulates brain maintenance in presymptomatic frontotemporal dementia

Objective Cognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time. Methods Two-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling. Results Highly educated at-risk subjects had better cognition and higher grey matter volume at baseline;moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers. Conclusions This longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD

Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Objective A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay. Methods We used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS. Results and conclusions We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts

Early symptoms in symptomatic and preclinical genetic frontotemporal lobar degeneration

Funder: UK Medical Research CouncilFunder: The Bluefield ProjectFunder: NIHR Cambridge Biomedical Research CentreFunder: Weston Brain InstituteFunder: Swedish Brain FoundationFunder: StratNeuro, Swedish DemensfondenFunder: NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research FacilityFunder: The Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grantFunder: Karolinska Institutet Doctoral FundingFunder: Stockholm County Council ALFFunder: Swedish Alzheimer FoundationObjectives: The clinical heterogeneity of frontotemporal dementia (FTD) complicates identification of biomarkers for clinical trials that may be sensitive during the prediagnostic stage. It is not known whether cognitive or behavioural changes during the preclinical period are predictive of genetic status or conversion to clinical FTD. The first objective was to evaluate the most frequent initial symptoms in patients with genetic FTD. The second objective was to evaluate whether preclinical mutation carriers demonstrate unique FTD-related symptoms relative to familial mutation non-carriers. Methods: The current study used data from the Genetic Frontotemporal Dementia Initiative multicentre cohort study collected between 2012 and 2018. Participants included symptomatic carriers (n=185) of a pathogenic mutation in chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN) or microtubule-associated protein tau (MAPT) and their first-degree biological family members (n=588). Symptom endorsement was documented using informant and clinician-rated scales. Results: The most frequently endorsed initial symptoms among symptomatic patients were apathy (23%), disinhibition (18%), memory impairments (12%), decreased fluency (8%) and impaired articulation (5%). Predominant first symptoms were usually discordant between family members. Relative to biologically related non-carriers, preclinical MAPT carriers endorsed worse mood and sleep symptoms, and C9orf72 carriers endorsed marginally greater abnormal behaviours. Preclinical GRN carriers endorsed less mood symptoms compared with non-carriers, and worse everyday skills. Conclusion: Preclinical mutation carriers exhibited neuropsychiatric symptoms compared with non-carriers that may be considered as future clinical trial outcomes. Given the heterogeneity in symptoms, the detection of clinical transition to symptomatic FTD may be best captured by composite indices integrating the most common initial symptoms for each genetic group

Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Ventricular volume expansion in presymptomatic genetic frontotemporal dementiaMRC, NIHR, Wellcome Trus

The Benson Complex Figure Test detects deficits in visuoconstruction and visual memory in symptomatic familial frontotemporal dementia: A GENFI study

Objective: Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation carriers, and to explore its cognitive and neuroimaging correlates.Method: We included cross-sectional data from 332 presymptomatic and 136 symptomatic mutation carriers (GRN, MAPT or C9orf72 mutations), and 290 controls in the GENFI consortium. We examined gene-specific differences between mutation carriers (stratified by CDR (R) NACC-FTLD score) and controls using Quade's / Pearson X2 tests. We investigated associations with neuropsychological test scores and grey matter volume using partial correlations and multiple regression models respectively.Results: No significant differences were found between groups at CDR (R) NACC-FTLD 0-0.5. Symptomatic GRN and C9orf72 mutation carriers had lower Copy scores at CDR (R) NACC-FTLD >= 2. All three groups had lower Recall scores at CDR (R) NACC-FTLD >= 2, with MAPT mutation carriers starting at CDR (R) NACC-FTLD >= 1. All three groups had lower Recognition scores at CDR (R) NACC FTLD >= 2. Performance correlated with tests for visuoconstruction, memory, and executive function. Copy scores correlated with frontal-subcortical grey matter atrophy, while Recall scores correlated with temporal lobe atrophy. Conclusions: In the symptomatic stage, the BCFT identifies differential mechanisms of cognitive impairment depending on the genetic mutation, corroborated by gene-specific cognitive and neuroimaging correlates. Our findings suggest that impaired performance on the BCFT occurs relatively late in the genetic FTD disease process. Therefore its potential as cognitive biomarker for upcoming clinical trials in presymptomatic to early-stage FTD is most likely limited