Theory of Mind in Huntington's Disease: A Systematic Review of 20 Years of Research.

Background: People with Huntington's disease (HD) exhibit neurocognitive alterations throughout the disease, including deficits in social cognitive processes such as Theory of Mind (ToM). Objective: The aim is to identify methodologies and ToM instruments employed in HD, alongside relevant findings, within the scientific literature of the past two decades. Methods: We conducted a comprehensive search for relevant papers in the SCOPUS, PubMed, APA-PsyArticles, Web of Science, Redalyc, and SciELO databases. In the selection process, we specifically focused on studies that included individuals with a confirmed genetic status of HD and investigated ToM functioning in patients with and without motor symptoms. The systematic review followed the PRISMA protocol. Results: A total of 27 papers were selected for this systematic review, covering the period from 2003 to 2023. The findings consistently indicate that ToM is globally affected in patients with manifest motor symptoms. In individuals without motor symptoms, impairments are focused on the affective dimensions of ToM. Conclusions: Based on our analysis, affective ToM could be considered a potential biomarker for HD. Therefore, it is recommended that ToM assessment be included as part of neuropsychological evaluation protocols in clinical settings. Suchinclusion could aid in the identification of early stages of the disease and provide new opportunities for treatment, particularly with emerging drugs like antisense oligomers. The Prospero registration number for this review is CRD42020209769.

Impulsive and Omission Errors: Potential Temporal Processing Endophenotypes in ADHD.

Temporal processing (TP) is associated with functions such as perception, verbal skills, temporal perspective, and future planning, and is intercorrelated with working memory, attention, and inhibitory control, which are highly impaired in individuals with attention deficit hyperactivity disorder (ADHD). Here we evaluate TP measures as potential endophenotypes in Caribbean families ascertained from probands affected by ADHD. A total of 232 individuals were recruited and clinically evaluated using an extensive battery of neuropsychological tasks and reaction time (RT)-based task paradigms. Further, the heritability (genetic variance underpinning phenotype) was estimated as a measure of the genetics apportionment. A predictive framework for ADHD diagnosis was derived using these tasks. We found that individuals with ADHD differed from controls in neuropsychological tasks assessing mental control, visual-verbal memory, verbal fluency, verbal, and semantic fluency. In addition, TP measures such as RT, errors, and variability were also affected in individuals with ADHD. Moreover, we determined that only omission and commission errors had significant heritability. In conclusion, we have disentangled omission and commission errors as possible TP endophenotypes in ADHD, which can be suitable to assess the neurobiological and genetic basis of ADHD. A predictive model using these endophenotypes led to remarkable sensitivity, specificity, precision and classification rate for ADHD diagnosis, and may be a useful tool for patients' diagnosis, follow-up, and longitudinal assessment in the clinical setting.

ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurobehavioral disorder that affects children worldwide, with detrimental long-term consequences in affected individuals. ADHD-affected patients display visual-motor and visuospatial abilities and skills that depart from those exhibited by non-affected individuals and struggle with perceptual organization, which might partially explain impulsive responses. Endophenotypes (quantifiable or dimensional constructs that are closely related to the root cause of the disease) might provide a more powerful and objective framework for dissecting the underlying neurobiology of ADHD than that of categories offered by the syndromic classification. In here, we explore the potential presence of the linkage and association of single-nucleotide polymorphisms (SNPs), harbored in genes implicated in the etiology of ADHD (ADGRL3, DRD4, and FGF1), with cognitive endophenotypes related to working memory and perceptual organization in 113 nuclear families. These families were ascertained from a geographical area of the Caribbean coast, in the north of Colombia, where the community is characterized by its ethnic diversity and differential gene pool. We found a significant association and linkage of markers ADGRL3-rs1565902, DRD4-rs916457 and FGF1-rs2282794 to neuropsychological tasks outlining working memory and perceptual organization such as performance in the digits forward and backward, arithmetic, similarities, the completion of figures and the assembly of objects. Our results provide strong support to understand ADHD as a combination of working memory and perceptual organization deficits and highlight the importance of the genetic background shaping the neurobiology, clinical complexity, and physiopathology of ADHD. Further, this study supplements new information regarding an ethnically diverse community with a vast African American contribution, where ADHD studies are scarce.

Control de la interferencia en el trastorno por déficit de atención e hiperactividad (TDAH): revisión / Interference Control in Attention Deficit and Hyperactivity Disorder (ADHD): Review

Resumen Introducción: Investigaciones sobre el trastorno por déficit de atención e hiperactividad (TDAH) han evidenciado alteraciones en los procesos inhibitorios, en especial en el control de la interferencia, lo que explicaría las dificultades de los niños con TDAH para inhibir estímulos distractores y controlar su comportamiento. Objetivo: Identificar la literatura científica disponible sobre el desempeño en tareas que evalúan el control de la interferencia en niños con TDAH. Método: Se realizó una búsqueda de artículos científicos en las bases de datos de Pubmed, Scopus, Web of Sciencie con los términos ADHD (Attention Deficit Hyperactivity Disorder), Interference Control, Stroop y Flanker, publicados entre los años 2010 y 2017. Se identificaron 520 artículos, después de aplicar los criterios de inclusión y exclusión se seleccionaron 33 para hacer el análisis descriptivo. Resultados: El control de la interferencia se ve afectado en niños con TDAH, evidenciado en mayores tiempos de reacción, de ejecución, variabilidad de respuesta y porcentaje de errores, principalmente en los ensayos incongruentes. Igualmente, se mostraron patrones de activación cortical alterados y variaciones en potenciales evocados cognitivos. Conclusiones: El control de la interferencia se encuentra alterado en niños con TDAH, y el uso de más de un método de evaluación de los niños con este Trastorno puede ser útil para brindar más información del funcionamiento en el control de la interferencia en términos de tiempo y precisión en las tareas.

Abstract Introduction: Research on attention deficit hyperactivity disorder (ADHD) has shown alterations in interference control, which would explain the difficulties of children with ADHD to inhibit distracting stimuli and regulate their behavior. Objective: identifying available scientific literature about performance on task that evaluate the interference control in children with ADHD. Method: a search on Pubmed, Scopus and Web of Science databases with the terms ADHD, interference control, Stroop and Flanker, published between 2010 and 2017 was performed. 520 articles were identified, after applying the inclusion and exclusion criteria 33 articles were selected for descriptive analysis. Results: interference control is affected in children with ADHD, evidenced in greater reaction and execution times, variability of response and a high errors rate, primarily in incongruent trials. Altered cortical activation patterns and variations in cognitive evoked potentials were also shown. Conclusions: Interference control is altered in children with ADHD, the use of more than one evaluation method may be useful to provide more information on the functioning of interference control in terms of time and accuracy on tasks.

Prepotent response inhibition and reaction times in children with attention deficit/hyperactivity disorder from a Caribbean community.

Impairment in inhibitory control has been postulated as an underlying hallmark of attention deficit/hyperactivity disorder (ADHD), which can be utilized as a quantitative trait for genetic studies. Here, we evaluate whether inhibitory control, measured by simple automatized prepotent response (PR) inhibition variables, is a robust discriminant function for the diagnosis of ADHD in children and can be used as an endophenotype for future genetic studies. One hundred fifty-two school children (30.9% female, 67.8% with ADHD) were recruited. The ADHD checklist was used as the screening tool, whilst the DSM-IV Mini International Neuropsychiatry Interview, neurologic interview and neurologic examination, and the WISC III FSIQ test were administered as the gold standard procedure to assert ADHD diagnosis. A Go/No-Go task using a naturalistic and automatized visual signal was administered. A linear multifactor model (MANOVA) was fitted to compare groups including ADHD status, age, and gender as multiple independent factors. Linear discriminant analysis and the receiver operating characteristic curve were used to assess the predictive performance of PR inhibition variables for ADHD diagnosis. We found that four variables of prepotent response reaction time- and prepotent response inhibition established statistically significant differences between children with and without ADHD. Furthermore, these variables generated a strong discriminant function with a total classification capability of 73, 84% specificity, 68% sensitivity, and 90% positive predictive value for ADHD diagnosis, which support reaction times as a candidate endophenotype that could potentially be used in future ADHD genetic research.

Conglomerados de clases latentes en 408 miembros de 120 familias nucleares de Barranquilla con un caso índice afectado de trastorno de atención hiperactividad (TDAH) / Latent class clusters in 408 members of 120 nuclear families from Barranquilla with a proband attention deficit hyperactivity disorder (adhd) affected case

Resumen Introducción: el análisis de conglomerados de clases latentes (ACCL) es un procedimiento estadístico para agrupamientos, dependiendo de la respuesta a cada ítem. Se ha usado con el trastorno de atención hiperactividad (TDAH), para derivar tipos sutiles de casos en estudios genéticos. Objetivo: analizar los CCL de 408 miembros de 120 familias con un caso índice de TDAH, en relación con los síntomas registrados en la entrevista psiquiátrica. Pacientes y métodos: a partir de un caso índice (niño escolarizado de Barranquilla con diagnóstico estándar de oro de TDAH) se construyeron familias nucleares, las cuales de evaluaron para el diagnóstico de TDAH y comorbilidades. La muestra fue de 408 miembros de 120 familias, edad 26,6 ± 15,4 años. Con el programa para computador Latent-Gold 4,0 se hizo el ACCL con la respuesta nominal para cada síntoma de TDAH, y la presencia o no de comorbilidades con TOD y TDC. Se usó el sexo y la edad como covariables categóricas. Se hizo un análisis cruzado de cada conglomerado con el diagnóstico estándar de oro. Resultados: el mejor modelo (índices de verosimilitud) fue de 6 CCL (p Bootstrap = 0,08). El conglomerado 1 (32,5 %) son adultos, predominio de sexo femenino, probabilidad < 20 % de síntomas y comorbilidades. El segundo (17,4 %) son adultos y niños de sexo masculino con 40 a 80 % de síntomas de TDAH combinado. El grupo tres (15,7 %) son niños con ~100 % síntomas de TDAH combinado, TOD y TDC. El cuarto conglomerado (14,3 %) son adultos de ambos sexos con 20 a 50 % probabilidades de hiperactividad-impulsividad, TOD (70 %) y TDC (40 %). El grupo 5 (10,6 %) en un 80 % adultos con 30 a 90 % probabilidades de inatención sin comorbilidades. El conglomerado 6 (9,5 %) con altas probabilidades de síntomas de inatención. Conclusiones: se derivaron 6 CCL. Cuatro conglomerados son de afectados, 1 de no afectados y 1 con similar proporción de afectados y no afectados, los cuales podrían ser usados en análisis con marcadores genéticos de susceptibilidad para TDAH.

Summary Introduction: Latent class cluster analysis (LCCA) is a statistical procedure to sort a sample, according to item response of each member of a sample. It has been used with ADHD in order to derive mild cases for genetic studies. Objective: To analyze LCC from 408 members of 120 nuclear families with a ADHD proband, related to registered symptoms obtained with a structured psychiatric interview. Patient and methods: From a proband (school -gold standard- ADHD affected child from Barranquilla) nuclear families were recruited, which were assess for ADHD and comorbidities diagnoses. Sample was 408 members of 120 nuclear families, mean age 26,6 ± 15,4 years old. Using Latent Gold 4,0 software, an ACCL with each ADHD categorical symptoms, and comorbidities with ODD and CD was run. Gender and age were used as categorical active covariables. A cross tabulation analysis between LCC and ADHD gold standard diagnosis was done. Results: The best model (maximum likelihood index) was a 6 LCC (p Bootstrap = 0,08). Cluster 1 (32,5%) were predominantly female adults with low (< 20%) probability of ADHD symptoms. Cluster 2 (17,4%) were adults and children with 40 to 80% probabilities of combined ADHD symptoms. Cluster 3 (15,7%) were children with ~100% of ADHD combined symptoms with ODD and CD comorbidities. Cluster 4 (14,3%) were adults of both genders with 20 to 50% probabilities of hyperactivity - impulsivity and ODD (70%) and CD (40%). Cluster 5 (10,6%) were 80% adults with 30 to 90% probabilities of inattentive symptoms without comorbidities. Cluster 6 (9,5%) had high probabilities of inattentive symptoms. Conclusions: A 6 LCC model was obtained. Four LCC were ADHD affected, one was unaffected and one with similar proportion of affected and unaffected members, which would are able to be used for genetic analyses with ADHD susceptibility gene markers.

Déficit en habilidades sociales en niños con Trastorno por Déficit de Atención-Hiperactividad, evaluados con la Escala BASC / Déficit em habilidades sociais em crianças com Transtorno por Déficit de Atenção-Hiperatividade, avaliados com a escala BASC / Social skills deficits in children diagnosed with Attention Deficit Hyperactivity Disorder evaluated with the BASC scale

Se analizaron las Habilidades Sociales (HS) de 159 niños de ambos sexos, escolarizados, con Trastorno por Déficit de Atención-Hiperactividad (TDAH), entre los 6 y los 11 años de edad. La valoración de las HS se realizó con la escala Behavioral Assessment System for Children para padres y maestros. Los resultados mostraron que los niños con TDAH presentan puntajes más bajos en las dimensiones de habilidades sociales como escuchar, esperar turnos, reconocer señales sociales y tener capacidad de adaptabilidad. Sin embargo, en compañerismo, los participantes con TDAH combinado poseen habilidades semejantes a los no afectados. Esto replantea lo encontrado en la mayoría de los estudios en donde únicamente se evidencian deficiencias...

The study analyzed the Social Skills (SS) of 159 male and female school children between the ages of 6 and 11, suffering from Attention Deficit Hyperactivity Disorder (ADHD). The evaluation of SS was carried out with the Behavioral Assessment System for Children for use by parents and teachers. The results showed that children with ADHD feature lower scores in social skills such as listening, respecting turns, recognizing social signals, and adaptability. However, participants with ADHD proved to have companionship skills similar to those of unaffected children. This makes it necessary to rethink the findings of the majority of studies, which only reveal deficiencies...

Analisaram-se as Habilidades Sociais (HS) de 159 crianças, escolarizadas, com Transtorno por Déficit de Atenção-Hiperatividade (TDAH), entre 6 e 11 anos de idade. A valoração das HS se realizou com a escala Behavioral Assessment System for Children para pais e mestres. Os resultados mostraram que as crianças com TDAH apresentam pontuações mais baixas nas dimensões de HS como escutar, esperar a vez, reconhecer sinais sociais e ter capacidade de adaptabilidade. Contudo, em companheirismo, os participantes com TDAH combinado possuem habilidades semelhantes aos não afetados. Isso repropõe o encontrado na maioria dos estudos nos quais unicamente se evidenciam deficiências...

Uso de una escala comportamental Wender Utah para evaluar en retrospectiva trastorno de atención-hiperactividad en adultos de la ciudad de Barranquilla / Using a Wender Utah behavioral scale to assess with hindsight adults suffering from attention-hyperactivity disorder in the city of Barranquilla

Los cuestionarios comportamentales son herramientas eficaces para caracterizar el Trastorno por Déficit de Atención e Hiperactividad (TDAH) en la edad adulta. Se determinó de forma retrospectiva, las características conductuales de adultos afectados con TDAH, utilizando la Escala Wender Utah (WURS). La muestra estuvo compuesta por 102 adultos pertenecientes a 51 familias nucleares de la ciudad de Barranquilla. El diagnóstico de TDAH se realizó aplicando una entrevista estructurada psiquiátrica para adultos validada en Colombia y usada en estudios para genética del TDAH. Se realizó un examen neurológico y una evaluación neuropsicológica. Se analizaron las puntuaciones de corte y se calculó el tamaño del efecto, la sensibilidad y la especificidad de la escala, hallándose diferencias clínica y estadísticamente significativas en las puntuaciones de la WURS, mostrando tamaños del efecto de grandes a enormes. La escala permite diferenciar los sujetos afectados de los no afectados demostrando la existencia de síntomas del TDAH de manera retrospectiva. Es importante resaltar que la WURS puede ser usada como instrumento para el rastreo de síntomas de TDAH en el adulto, sin embargo se hace necesario complementar sus resultados con otros instrumentos para la comprobación multimodal del diagnóstico.

The behavioral questionnaires are effective tools to characterize the Attention Deficit Hyperactivity Disorder (ADHD) in adulthood. It was determined the behavioral characteristics of adults with ADHD in retrospect by using the Wender Utah Rating Scale (WURS). The sample consisted of 102 adults from 51 nuclear families in the city of Barranquilla. The diagnosis of ADHD was conducted using a structured psychiatric interview validated in Colombia, which is also used for genetic studies of ADHD. A neurological examination and a neuropsychological evaluation were made. The cutting scores were analyzed and the effect size, sensitivity and specificity of the scale were calculated. It was found that there are clinical and statistical significant differences in WURS scores, which showed large to enormous effect sizes. The scale distinguishes affected subjects from the unaffected ones, which proves the existence of ADHD symptoms in retrospect. It is important to highlight the WURS can be used as a tool for screening adult ADHD symptoms. However, it is necessary to complement its results with other tools for multimodal diagnostic testing.