El Reto Asistencial y Educativo del Autismo Grave

Una de cada tres personas con autismo presentaría el llamado autismo grave. No existe una definición estandarizada para el autismo grave, pero el término se suele utilizar para aquellas personas que apenas tienen noción del lenguaje, asociado a una disminución de la capacidad cognitiva y que pueden llevar a cabo las tareas de la vida cotidiana con dificultad. A pesar de la mayor visibilización del autismo en la sociedad y de las iniciativas para mejorar la atención que recibe, no se está desarrollando el conocimiento sobre autismo grave. Así, es preciso estimular la investigación sobre prevalencia, buenas prácticas y tratamientos con el objetivo de mejorar las políticas dirigidas a esta población que fomenten recursos de soporte e intervenciones eficaces en todos los entornos

Internet-based psychotherapy in children with obsessive-compulsive disorder (OCD): protocol of a randomized controlled trial

Background: Obsessive-compulsive disorder (OCD) in children can lead to a huge burden on the concerned patients and their family members. While successful state-of-the art cognitive behavioral interventions exist, there is still a lack of available experts for treatment at home, where most symptoms manifest. Internet-based cognitive behavioral therapy (iCBT) could overcome these restrictions; however, studies about iCBT in children with OCD are rare and mostly target computerized self-help resources and only email contact with the therapist. Therefore, we intended to build up and to evaluate an iCBT approach for children with OCD, replacing successful elements of traditional in-office face-to-face CBT, with face-to-face teleconferences, online materials, and apps. Methods: With the help of a pilot feasibility study, we developed the iCBT consisting of 14 teleconference sessions with the child and parents. The sessions are supported by an app assessing daily and weekly symptoms and treatment course completed by children and parents. Additionally, we obtain heart rate and activity scores from the child via wristbands during several days and exposure sessions. Using a waiting list randomized control trial design, we aim to treat and analyze 20 children with OCD immediately after a diagnostic session whereas the control group of another set of 20 OCD patients will be treated after waiting period of 16 weeks. We will recruit 30 patients in each group to take account for potential dropouts. Outcomes for the treatment group are evaluated before randomization (baseline, t0), 16 weeks (end of treatment, t1), 32 weeks (follow-up 1, t2), and 48 weeks after randomization (follow-up 2, t3). For the waiting list group, outcomes are measured before the first randomization (baseline), at 16 weeks (waiting list period), 32 weeks (end of treatment), 48 weeks after the first randomization (follow-up I), and 64 weeks after the first randomization (follow-up II). Discussion: Based on our experience of feasibility during the pilot study, we were able to develop the iCBT approach and the current study will investigate treatment effectiveness. Building up an iCBT approach, resembling traditional in-office face-to-face therapy, may ensure the achievement of well-known therapy effect factors, the acceptance in both patients and clinicians, and the wide distribution within the health system. Trial registration: ClinicalTrials.gov NCT05037344 . Registered May 2019, last release August 13th, 2021

White matter diffusion estimates in obsessive-compulsive disorder across 1,653 individuals: Machine learning findings from the ENIGMA OCD Working Group

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1,336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) “OCD vs. healthy controls'' (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) “unmedicated OCD vs. healthy controls” (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) “medicated OCD vs. unmedicated OCD” (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6–79.1 in adults; 35.9–63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research

Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD

Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases

Altres ajuts: Generalitat de Catalunya, Departament de Salut; Generalitat de Catalunya, Departament d'Empresa i Coneixement i CERCA Program; Ministerio de Ciencia e Innovación; Instituto Nacional de Bioinformática; ELIXIR Implementation Studies (CNAG-CRG); Centro de Investigaciones Biomédicas en Red de Enfermedades Raras; Centro de Excelencia Severo Ochoa; European Regional Development Fund (FEDER).Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%)

Psicopatología en familiares de primer grado de niños y adolescentes con trastorno obsesivo-compulsivo

[spa] El Trastorno Obsesivo-Compulsivo (TOC) como entidad clínica está definido en el DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, DSM-IV; American Psychiatric Association, 1984) y consiste en el desarrollo por parte del individuo de obsesiones o compulsiones que le provoquen un sufrimiento importante o que interfieran en sus actividades habituales y su funcionamiento social. Se denominan "Obsesiones" las ideas, pensamientos, imágenes o impulsos recurrentes y persistentes que se experimentan, al menos inicialmente, como intrusivos y sin sentido, mientras que las compulsiones serían conductas intencionadas, repetitivas y con una finalidad, que se llevan a cabo en respuesta a una obsesión, o de acuerdo con ciertas normas o de una forma estereotipada. La conducta compulsiva estaría dirigida a neutralizar o prevenir el malestar o algún suceso o la situación temida; sin embargo, la actividad no está relacionada de manera realista con lo que se pretende neutralizar o prevenir o bien es claramente excesiva, por lo que la propia persona acaba reconociendo que su comportamiento es excesivo o irracional. Aunque el TOC puede afectar a niños, adolescentes y adultos (Flament y cols, 1988; Karno y cols, 1988; Swedo y cols, 1989; Rasmussen y cols, 1992; Weissman y cols, 1994), desde que se identificó esta patología a comienzos del siglo XX se ha podido comprobar que buena parte de los cuadros de TOC se desarrollan durante la infancia o tienen su origen en la misma. Es importante tener en cuenta que los síntomas del TOC tienen un grado de interferencia variable en las actividades cotidianas, por lo que es preciso proceder a su correcta identificación y tratamiento. En efecto, las tareas escolares, el aseo y otros aspectos básicos en la formación del niño como individuo pueden estar comprometidos por la dedicación a los síntomas obsesivo-compulsivos. La prevalencia estimada para el TOC en la población infanto-juvenil es 1-3% (Flament y cols, 1988; Valleni-Basile, 1994, Zohar y cols, 1993), aproximadamente igual que la prevalencia de TOC referida en población adulta (Weissman y cols, 1994). Parece existir una distribución bimodal en la edad de inicio, con un pico en la infancia (hacia los 11 años) y otro en la adolescencia y primeros años de la vida adulta (Weissman y cols, 1994). En los estudios de adultos con diagnóstico de TOC, la obtención de la edad de inicio es retrospectiva, y los criterios para establecer el comienzo del trastorno pueden variar, dado que algunos autores toman los primeros síntomas subclínicos como el momento del inicio frente a los que consideran el comienzo del trastorno la aparición de síntomas acompañados de una interferencia significativa. La presente tesis tiene como punto de partida la constatación que existen diferencias significativas, en cuanto a psicopatología, entre los familiares de menores con TOC y familiares de menores sin patología psiquiátrica. Los objetivos marcados son los siguientes: 1. Identificar la prevalencia de trastornos psiquiátricos (TOC y otros) en familiares de primer grado de niños y adolescentes con diagnóstico de TOC, comparándola con la de familiares de primer grado de niños y adolescentes sin patología psiquiátrica. 2. Identificar los trastornos psiquiátricos de inicio reciente que se presentan en familiares de primer grado de niños y adolescentes con diagnóstico de TOC y compararlos con los de familiares de primer grado de niños y adolescentes sin patología psiquiátrica. 3. Identificar la prevalencia de trastornos de personalidad en los familiares de primer grado de niños y adolescentes diagnosticados de TOC, comparándola con la de familiares de primer grado de niños y adolescentes sin patología psiquiátrica. 4. Describir las dimensiones normales de la personalidad de familiares de primer grado de pacientes con TOC pediátrico y compararlas con las de familiares de primer grado de niños sin patología psiquiátrica. 5. Describir las características clínicas, la fenomenología y la comorbilidad de una muestra de niños con TOC pediátrico

Teoría de la mente en trastornos del neurodesarrollo: más allá del trastorno del espectro autista

Resumen: Introducción: La teoría de la mente (ToM) es la capacidad humana de percibir, interpretar y atribuir los estados mentales de las otras personas y la alteración de esta función cognitiva es un síntoma nuclear del trastorno del espectro autista (TEA). Hay otros trastornos del neurodesarrollo como el trastorno obsesivo-compulsivo de inicio en la infancia (TOC) y el síndrome de Tourette (ST), que pueden presentarse con disfunciones cognitivas, y en los que la ToM ha sido menos estudiada, especialmente en población juvenil. El objetivo de este estudio fue comparar la ToM avanzada entre grupos de jóvenes con diagnóstico de TOC, ST o TEA y un grupo de controles sanos. Métodos: Se entrevistaron clínicamente a varones de entre 11 y 17 años con diagnóstico principal de TOC (n = 19), ST (n = 14), TEA (n = 18), y un grupo control de sujetos sanos (n = 20). Se les administró instrumentos de estimación de cociente intelectual, severidad de los síntomas psiquiátricos y las pruebas para evaluar la ToM: la tarea Historias de la vida cotidiana y el Test de la mirada. Resultados: Los jóvenes con ST presentan dificultades similares para resolver tareas de ToM avanzada al nivel de los pacientes con TEA, a diferencia de los pacientes con TOC de inicio en la infancia que presentan resultados similares a los controles sanos. Conclusiones: La ToM está alterada en otros trastornos del neurodesarrollo más allá del TEA, como en el ST. Abstract: Introduction: Theory of mind (ToM) is the human ability to perceive, interpret, and attribute the mental states of other people, and the alteration of this cognitive function is a core symptom of autistic spectrum disorder (ASD). In such other neurodevelopmental disorders as childhood-onset obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) that can present with cognitive dysfunctions, ToM has been less extensively studied, especially in the young population. The aim of the study was to compare advanced ToM between groups of young people diagnosed with OCD, TS, or ASD and a control group. Methods: Clinical interviews were conducted with male patients aged between 11 and 17 years with a main diagnosis of OCD (n = 19), TS (n = 14), or ASD (n = 18), and a control group (n = 20). We administered instruments for estimating intelligence quotient and severity of psychiatric symptoms, and tasks to evaluate ToM (the “Stories from everyday life” task and the “Reading the mind in the eyes” test). Results: Young people with TS and with ASD present similar difficulties in solving advanced ToM tasks, whereas patients with childhood-onset OCD present similar results to controls. Conclusions: ToM is altered in other neurodevelopmental disorders beyond ASD, such as TS

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses