Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Background and Purpose—This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment ...

Vascular Contributions to Cognitive Impairment and Dementia A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Application of the experimental design of genome-wide association studies (GWASs) is now 10 years old (young), and here we review the remarkable range of discoveries it has facilitated in population and complex-trait genetics, the biology of diseases, and translation toward new therapeutics. We predict the likely discoveries in the next 10 years, when GWASs will be based on millions of samples with array data imputed to a large fully sequenced reference panel and on hundreds of thousands of samples with whole-genome sequencing data.

10 Years of GWAS Discovery: Biology, Function, and Translation

The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.

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Synaptic, transcriptional and chromatin genes disrupted in autism

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Adolescents are at high risk of incident psychopathology. Fleeting psychotic experiences (PEs) that emerge in young people in response to stress may be warning signs that are missed by research that fails to study stressed populations, such as late high school and college/university students. Our aim in this systematic review was to conduct a meta‐analysis that estimates prevalence rates of PEs in students, and to assess whether these rates differ by gender, age, culture, and COVID‐19 exposure.

Prevalence and risk factors of self‐reported psychotic experiences among high school and college students: A systematic review, meta‐analysis, and meta‐regression

Background Patients suffering from schizophrenic psychosis show reduced synaptic connectivity compared to healthy individuals. Furthermore, the use of cannabis often precedes the onset of schizophrenic psychosis. Therefore, we investigated whether consumption of cannabis has an impact on the methylation pattern of schizophrenia candidate genes concerned with the development and preservation of synapses and synaptic function. Methods Fifty blood samples of outpatients affected by treatment-resistant schizophrenic psychosis were collected in the outpatient department of Ch Ste Anne/INSERM (Paris, France). Extracted DNA was sent to the LMN/MHH (Hanover, Germany) where DNA samples were bisulfite converted. The methylation patterns of the promoter region of neuregulin 1 (NRG1), neurexin (NRXN1), disrupted in schizophrenia 1 (DISC1), and microtubule-associated-protein tau (MAPT) were then analysed by sequencing according to Sanger. Results In NRXN1 the group of non-consumer patients showed a methylation rate slightly lower than controls. In patients with preliminary use of tetrahydrocannabinol (THC) the NRXN1 promoter turned out to be methylated almost two times higher than in non-consumer patients. In MAPT, non-consumer patients showed a significant lower mean methylation rate in comparison to controls. In THC-consuming patients the difference compared with controls became less. NRG1 and DISC1 showed no significant differences between groups, whereas DISC1 appeared to be not methylated at all. Conclusion In MAPT and NRXN1 mean methylation rates were lower in non-consumer patients compared with controls, which seems to be a compensatory mechanism. With consumption of THC, mean methylation rates were increased: in the case of MAPT compared with controls, and in NRXN1 even significantly beyond that. Methylation of NRG1 and DISC1 seems not to be affected by the psychiatric disorder or by consumption of THC.

Differential Methylation Pattern of Schizophrenia Candidate Genes in Tetrahydrocannabinol-Consuming Treatment-Resistant Schizophrenic Patients Compared to Non-Consumer Patients and Healthy Controls.

The heterogeneity of Schizophrenia disease has been a major pitfall for identifying the aetiological, genetic or environmental factors. Age at onset or several other quantitative variables could allow for categorizing more homogeneous subgroups of patients, although there is little information on which are the boundaries for such categories. The Bayesian networks classifier approach is one of the most popular formalisms for reasoning under uncertainty. We used this approach to determine the best cut-off point for three continuous variables (i.e. age at onset of schizophrenia (AFC* & AFE**) and neurological soft signs (NSS)) with a minimal loss of information, using a data set including genotypes of selected candidate genes for schizophrenia.

Delimiting cut-off of age at onset in Schizophrenia using Bayesian network

Les troubles schizophreniques debutent en moyenne chez l'adulte jeune mais ils sont precedes dans 75 % des cas d'une phase dite prodromique. Les sujets concernes par cette phase prodromique sont dits a « haut risque » de psychose (environ 30 % de risque de developper un trouble psychotique dans les 2 ans). L'enjeu des programmes de detection est de determiner a priori les symptomes definissant la phase prodromique afin de mettre en place les mesures de prise en charge adequates pour differer, voire prevenir, l'apparition de la psychose et reduire la periode de psychose non traitee. La prescription d'antipsychotiques atypiques en presence de symptomes attenues n'est pas recommandee, alors qu'ils doivent etre prescrits rapidement si l'episode psychotique est confirme. Le reperage precoce des patients schizophrenes fait partie des missions des medecins generalistes a condition que ceux-ci puissent s'appuyer sur des equipes psychiatriques specialisees disponibles. L'intervention precoce doit etre fondee sur une evaluation poussee pour permettre de personnaliser la prise en charge, qui peut associer therapie cognitive, psychoeducation, et traitement des troubles associes (depression, abus de substance). La reduction de la duree de psychose non traitee passe aussi par des campagnes de sensibilisation pour ameliorer l'acces aux soins.

Early detection and early intervention in first episode psychosis

Les methodes de construction d'ontologies se sont fortement developpees au travers du traitement automatique du langage et de l'interet croissant aux corpus de donnees volumineux, engendrant un effacement progressif des acteurs du domaine au profit du traitement des donnees du domaine. Cependant, quelle que soit la ressource utilisee, la validation des ontologies demeure une question centrale de l'ingenierie des connaissances. Elle s'articule autour de deux problematiques complementaires : (1) la validation structurelle et (2) la validation semantique (de l'adequation au domaine modelise). Dans le premier cas, de nombreuses methodes ont vu le jour offrant des supports realisant automatiquement les tâches de validation. A contrario, les methodes pour la recherche du second cas sont encore peu nombreuses. Nous proposons dans cet article la methode LOVMI, mise en oeuvre pour la validation structurelle et semantique du module « facteurs sociaux et environnementaux des maladies psychiatriques » de notre ontologie ONTOPSYCHIA. Mots-cles : Ontologies, validation d'ontologies, evaluation d'ontologies, psychiatrie, facteurs sociaux et envi-ronnementaux.

https://hal.archives-ouvertes.fr/hal-01166359/document

Marie-Odile Krebs

Papers

Prevalence and risk factors of self‐reported psychotic experiences among high school and college students: A systematic review, meta‐analysis, and meta‐regression

Differential Methylation Pattern of Schizophrenia Candidate Genes in Tetrahydrocannabinol-Consuming Treatment-Resistant Schizophrenic Patients Compared to Non-Consumer Patients and Healthy Controls.

Delimiting cut-off of age at onset in Schizophrenia using Bayesian network

Early detection and early intervention in first episode psychosis

LOVMI : vers une méthode interactive pour la validation d'ontologies