El funcionamiento cognitivo como endofenotipo de la anorexia nerviosa. Estudio en familiares no afectados por la enfermedad / Cognitive functioning as an endophenotype of anorexia nervosa. A study in first-degree relatives unaffected by the disease

Resumen El perfil cognitivo de los pacientes con anorexia nerviosa se caracteriza por dificultades en la flexibilidad mental y en la coherencia central. El objetivo de este trabajo fue analizar si los familiares de primer grado no afectados de los pacientes presentan estas dificultades cognitivas, que podrían representar rasgos endofenotípicos de la enfermedad. Fueron estudiadas 34 mujeres: 17 familiares de primer grado (madres y hermanas) de pacientes con anorexia nerviosa y 17 controles sanos agrupados por edad y escolaridad. Se consideraron el índice de masa corporal, la ansiedad, la depresión, los síntomas obsesivo-compulsivos y los relacionados con los trastornos alimentarios. Se evaluó la coherencia central, mediante la copia de la Figura Compleja de Rey, y la flexibilidad mental, mediante el test de Stroop, el test de los trazos B y el test de fluencia fonológica. Los familiares de pacientes con anorexia nerviosa presentaron un menor rendimiento en las medidas de coherencia central (p < .05) y en fluencia fonológica (p < .05) que los controles sanos. Se observó una correlación entre el test de Stroop y los síntomas de depresión y trastornos alimentarios (p < .05). Los familiares de primer grado no afectados de pacientes con anorexia nerviosa presentaron dificultades en la coherencia central y, en menor grado, en la flexibilidad mental. Los resultados en los familiares indican que este perfil podría ser mediado genéticamente, constituyendo un rasgo característico de la anorexia nerviosa y, por ende, un posible candidato a endofenotipo neuropsicológico de esta enfermedad.

Abstract The cognitive profile of patients with anorexia nervosa is characterized by difficulties in central coherence and mental flexibility. Central coherence is defined by the ability to integrate incoming information in its own context, and weakness in central coherence is characterized by poor overall processing and superior detail processing. Mental flexibility is defined by the ability to change the course of a thought or action according to the demands of the environment. Alterations in this cognitive domain generate rigid and inflexible behavior. An open question in the literature is whether these cognitive characteristics are a transient state derived from the disease or whether they are stable traits associated with anorexia nervosa and endophenotypical features of this disease. The concept of endophenotype refers to the internal phenotype that is not clinically appreciable but can be observed indirectly through deficits that arise in the performance of certain neuropsychological tests. In recent years the search for endophenotypes has been renewed in the field of psychiatry as they would constitute an important route for the understanding of the biological and genetic bases of mental illnesses, constituting markers that allow a diagnosis before the onset of clinical symptomatology. For a cognitive marker to be considered an endophenotype it must meet a series of characteristics such as being measurable, inherited, found in patients with and without active disease and in first-degree relatives not affected by the disease. The aim of the present study was to assess whether difficulties in central coherence and mental flexibility are shared by unaffected first-degree relatives of patients with anorexia nervosa and thus constitute an endophenotypical feature of this disease. This is a cross-sectional, descriptive-comparative study in which 34 women participated: 17 unaffected first-degree relatives of patients with anorexia nervosa (mothers and sisters) and 17 healthy controls matched by age and education. For the study of central coherence the copy of Rey's Complex Figure was used and to assess set-shifting the Stroop test, the Trail Making Test B and the Phonological Fluency test were used. Demographic and clinical aspects such as age, educational level, body mass index, anxiety, depression, obsessive-compulsive and eating disorder related symptoms were also evaluated. First-degree relatives of patients with anorexia nervosa showed lower performance on measures of central coherence (p < .05) and phonological fluency (p < .05) than healthy controls. A correlation was observed between the Stroop test and depression and eating disorders symptoms (p < .05). The results of this study show that unaffected first-degree relatives of patients with anorexia nervosa presented alterations in central coherence and, to a lesser degree, in mental flexibility. These results, in addition to previous research in which difficulties persisted even after recovery, indicate that these alterations could be genetically mediated, constituting a characteristic trait of anorexia nervosa and therefore a possible candidate for neuropsychological endophenotype of this disease. Regarding practical implications of the study, the findings reinforce the importance of cognitive remediation treatments not only for patients with anorexia nervosa but also emphasize that they could be useful for unaffected family members. Taking into account that family intervention is a widely used tool in the psychological treatment of anorexia, improving the perception of the patient and his relatives about cognitive biases, could contribute to raising awareness of the disease, something that patients with anorexia nervosa do not usually have, and generate a positive impact on the response to treatment as a whole.

Study on prospective memory deficits of obsessive-compulsive disorder patients in the endophenotype framework / 四川精神卫生

ObjectiveTo study the prospective memory deficits of obsessive-compulsive disorder patients and unaffected first-degree relatives of patients， so as to validate the possibility of prospective memory as an endophenotype of obsessive-compulsive disorder. MethodsHealthy controls， obsessive-compulsive disorder patients and unaffected first-degree relatives of patients， each with 25 cases， matched for age， education， gender， IQ and marriage status were enrolled. The standardized prospective memory paradigm with a multi-trial design was conducted， and the accuracy was used as an indicator of prospective memory function. ResultsThe accuracy of event- and time-based prospective memory tasks of obsessive-compulsive disorder patients was lower than that of healthy controls， with statistical differences ［（0.74±0.24） vs. （0.88±0.13）， d=-0.140， P=0.044； （0.77±0.21） vs. （0.93±0.10）， d=-0.164， P=0.011］. The accuracy of event-based prospective memory task of unaffected first-degree relatives was also lower than that of healthy controls， with statistical difference ［（0.73±0.20） vs. （0.88±0.13）， d=-0.144， P=0.036］. ConclusionObsessive-compulsive disorder patients has extensive prospective memory deficits， indicating that prospective memory may be an endophenotype of obsessive-compulsive disorder.

Funciones cognitivas en la descendencia de pacientes con trastorno bipolar I / Psychopathological and neuropsychological profile in the offspring of patients with bipolar disorder type I

Resumen Objetivo: Describir las características neuropsicológicas de niños y adolescentes descendientes de padres con antecedentes de TB I, respecto a la aplicación de una prueba estandarizada de inteligencia. Materiales y métodos: Estudio observacional descriptivo de corte transversal, en donde los autores investigaron el Coeficiente Intelectual Total; Índice de compresión verbal; Índice de Razonamiento Perceptual; Índice de Memoria de trabajo; Índice de Velocidad de Procesamiento. Se evaluaron (n=30) descendientes al aplicar varias subpruebas de la Escala de inteligencia de Weschler para niños, (WISC -IV). Resultados: El Coeficiente Intelectual Total de los participantes con un 63,3% está por debajo del promedio de la curva de distribución normal, según la estandarización del test de inteligencia aplicado. Clasificando la tendencia de la muestra como un promedio normal bajo, en cuanto a la muestra evaluada. Los índices de memoria de trabajo y compresión verbal fueron las funciones cognitivas con puntuaciones más bajas en la muestra. Discusión: Nuestros hallazgos sugieren un riesgo en hijos de pacientes con TBI, que puede contribuir a un incremento cuantitativo de las alteraciones cognitivas, especialmente el índice de memoria de trabajo y compresión verbal. Estos hallazgos pueden sugerir un posible endofenotipo del TB I y su descendencia, en relación a la presentación temprana de alteraciones cognitivas en este grupo de riesgo. Dichos hijos podrían ser un punto de partida para realizar estudios que determinen predicción y realizar así un abordaje temprano.

Abstract Objective: To describe the neuropsychological characteristics of offspring children and adolescents of patients with bipolar disorder type 1 diagnosis through the application of a standardized intelligence test. Materials and methods: In this descriptive cross-sectional observational study, the authors investigated aspects such as Intelligence Quotient, Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index. Here, 30 descendants were evaluated by applying several subtests of the Wechsler Intelligence Scale for Children (WISC-IV). Results: The Total Intelligence Quotient of 63.3% of the participants is below the average of the Normal Distribution curve according to the standardization of the intelligence test applied which classifies the tendency of the sample as a low normal average. The working memory and verbal comprehension indexes were the cognitive functions with the lowest scores in the sample. Discussion: Our findings suggest a risk in children of patients with Bipolar Disorder type I, which may contribute to a quantitative increase of cognitive disorders, especially in terms of working memory and verbal comprehension indexes. These findings may indicate a possible endophenotype of Bipolar Disorder type I patients and their offspring in regards to the early manifestation of cognitive disorders in this risk group. These children could be a target for studies that determine prediction and thus perform an early treatment.

Estudios de agregación plaquetaria como endofenotipo de las alteraciones hereditarias de la fibra colágena / Platelet aggregation studies as an endophenotype of hereditary disorders of collagen fiber

Introducción: Las plaquetas contribuyen a la hemostasia y la interrupción heredada o adquirida; en sus procesos bioquímicos pueden alterar la función plaquetaria. Estos trastornos de agregación se han asociado a enfermedades genéticas con afectación del tejido conectivo como el síndrome Ehlers-Danlos, cuyo diagnóstico diferencial con el espectro de hipermovilidad articular resulta difícil clínica y molecularmente. Estas entidades con afectación en las fibras colágenas y diferente repercusión clínica precisan diferenciales en su diagnóstico clínico. Métodos: Se revisaron 353 historias clínicas de pacientes atendidos en el Servicio de Genética del Hospital Pediátrico William Soler desde septiembre del 2009 al 2012, con diagnóstico de hipermovilidad articular por criterios de Beighton y de Ehlers-Danlos según Villefranche (1997). Se incluyó a los pacientes de 5-18 años con resultados documentados del estudio de agregación plaquetaria, valorados por especialistas en hematología. Resultados: Se encontraron trastornos de agregación plaquetaria en 79 de 86 pacientes (92 por ciento). En 7 casos con hipermovilidad de 65 con este diagnóstico (10 por ciento), los resultados fueron negativos. Los 21 con síndrome Ehlers-Danlos tuvieron afectaciones con los fosfolípidos plaquetarios. La hipermovilidad articular estuvo asociada a la combinación difosfato de adenosina (ADP)-epinefrina y el Ehlers-Danlos a la combinación ADP-epinefrina-colágeno-fosfolípidos. Conclusiones: Los pacientes con hipermovilidad articular mostraron asociación a defectos de liberación de gránulos con agonistas como el ADP-epinefrina y los Ehlers-Danlos con la disponibilidad de los fosfolípidos, relacionados con el cambio de forma plaquetaria. Este resultado puede ser una herramienta para conocer el endofenotipo funcional plaquetario como elemento diferencial en los trastornos de la fibra colágena(AU)

Introduction: Platelets contribute to hemostasis and inherited or acquired interruption; in its biochemical processes it can alter platelet function. These aggregation disorders have been associated with genetic diseases with connective tissue involvement such as Ehlers-Danlos syndrome, whose differential diagnosis with the spectrum of joint hypermobility is clinically and molecularly difficult. These entities with involvement of the collagen fibers and different clinical repercussions require differentials in their clinical diagnosis. Methods: 353 medical records of patients attended in the Genetics service of the William Soler Pediatric Hospital from September 2009 to 2012, with a diagnosis of joint hypermobility by Beighton and Ehlers-Danlos criteria according to Villefranche (1997) were reviewed. Patients aged 5-18 years were included with documented results of the platelet aggregation study, assessed by specialists in hematology. Results: Platelet aggregation disorders were found in 79 of 86 patients (92 percent). In 7 cases with hypermobility of 65 with this diagnosis (10 percent), the results were negative. The 21 with Ehlers-Danlos syndrome had affectations with platelet phospholipids. Joint hypermobility was associated with the combination adenosine diphosphate (ADP) -epinephrine and the Ehlers-Danlos with the combination ADP-epinephrine-collagen-phospholipids. Conclusions: Patients with joint hypermobility showed an association to granule release defects with agonists such as ADP-epinephrine and Ehlers-Danlos with the availability of phospholipids, related to platelet shape change. This result can be a tool to know the platelet functional endophenotype as a differential element in collagen fiber disorders(AU)

Increased Expression of Interleukin-12 in Lesional Skin of Atopic Dermatitis Patients with Psoriasiform Features on Histopathology: An Immunohistochemical Study

Un cuarto de siglo de investigación genética en los trastornos neuropsiquiátricos en Costa Rica

El estudio de la base genética de los trastornos neuropsiquiátricos se inició en Costa Rica hace más de 25 años. En este tiempo se han realizado investigaciones enfocadas en diferentes trastornos: esquizofrenia, trastorno bipolar, demencia de Alzheimer, trastorno obsesivo compulsivo, trastorno obsesivo compulsivo, trastorno por déficit de atención y síndrome de Tourette. Los estudios realizados han tenido una amplia variación en lo que se refiere a diseño (ligamiento/asociación), muestra utilizada (familias/parejas de hermanos afectados/tríos), cobertura genómica (estudios con genes candidatos/tamizajes de todo el genoma) y definición del fenotipo (categoría diagnóstica/clasificación sindrómica/endofenotipo). Presentamos un resumen de los principales hallazgos genómicos obtenidos en estos estudios multidisciplinarios y discutimos la importancia, lecciones y retos de la investigación genética en trastornos psiquiátricos complejos.

In Costa Rica, the study of the genetic basis of neuropsychiatric disorders started more than 25 years ago. During this time, different research efforts have focused on several disorders: schizophrenia, bipolar disorder, Alzheimer's disease, obsessive-compulsive disorder, attention deficit/hyperactivity disorder, and Tourette syndrome. The studies have had a wide scope regarding design (linkage/association), sample used (families/sib pairs/trios), genome coverage (candidate gene studies/genome-wide scans), and phenotype definition (diagnostic category/syndromic classification/endophenotype). Here we present a summary of the main genomic findings of these multidisciplinary studies, and discuss the importance, lessons, and challenges of genetic research of complex psychiatric disorders.

Comparison of Cognitive Controls in Patients with Bipolar I Disorder and Their Unaffected First-Degree Relatives

OBJECTIVES: This study intended to identify the deficits of cognitive control among patients with bipolar I disorder and their first-degree relatives, and identify the possibility of cognitive control as an endophenotype of bipolar disorder. METHODS: The study included three groups: euthymic states patients with bipolar I disorder (n = 55), unaffected first-degree relatives of probands with bipolar I disorder (n = 30), and a healthy control group (n = 51), that was matched on age, sex, and years of education. The AX version of the continuous performance test (CPT) was used to examine cognitive control. Error rate, correct response times of each subsets (AX, BX, AY, BY), and d' as an indication of accuracy sensitivity index were calculated. Psychopathology, intelligence, and psychomotor speed were also assessed. RESULTS: Patients with bipolar I disorder showed significantly worse error rates in the AX (p = 0.01) and BX (p = 0.02) subsets and d' (p = 0.05) than the others. They also showed more delayed correct response times than the healthy control group and first-degree relatives in all subsets (p < 0.01). But first-degree relatives showed neither high error rates nor delayed correct response times than healthy control group. CONCLUSIONS: These findings suggest that cognitive control is impaired in bipolar I disorder but less likely to be an endophynotype of bipolar I disorder.

Cognitive function of remitted schizophrenia patients and their first-degree non-psychotic relatives / 重庆医学

Objective To explore difference of neuropsychological tests between the remitted schizophrenia patients and the first-degree non-psychotic relatives of schizophrenia patients,and to explore the possible endophenotypes in cognitive function.Methods The MATRICSTM consensus cognitive battery was administered to 86 remittent schizophrenia patients (the patient group),86 first-degree non-psychotic relatives of schizophrenia patients (the relative group),and 86 healthy people (the control group).Results Compared with the control group,the patients group and the relative group showed poor performance on trail making test,brief assessment of cognition,hopkins verbal learning,mazes,category fluency,emotional intelligence test and continuous performance test (P＜0.05).There were significantly lower performances in the patient group than the relative groups on hopkins verbal learning,mazes,emotional intelligence test and continuous performance test (P＜0.05).Conclusion The remitted schizophrenia patients and their first-degree non-psychotic relatives have selective deficits in cognition function,among them,verbal leaning,attention/vigilance,reasoning and problem solving and social cognition may be potential endophenotypes for schizophrenia.

Comparative study of neurological soft signs in remittent schizophrenia and non-psychotic first-degree relatives / 中国神经精神疾病杂志

Objective To examine the difference of neurological soft signs (NSS) among the remittent schizophrenia patients,first-degree non-psychotic relatives of schizophrenia patients and healthy controls.Methods The Cambridge Neurological Inventory (CNI) (the Chinese version) was administered to 86 remittent schizophrenia patients (patient group),86 first-degree non-psychotic relatives of schizophrenia patients (relative group) and 86 healthy controls (control group).Results Compared with relative group,NSS total-score,the subscore of motor coordination and sensory integration were significantly higher in patient group (P＜0.01).Compared with control group,NSS total-score,the subscore of motor coordination and sensory integration were significantly higher in patient group (P＜0.01).Compared with control group,NSS total-score and the subscore of motor coordination were significantly higher in relative group (P＜0.01).Conclusions The levels of NSS in remittent schizophrenia patients and their first-degree non-psychotic relatives are higher than normal control,and the patients have more NSS than their relatives.The motor coordination nay be a potential endophenotype for schizophrenia.

Comparison of Cognitive Control Deficits in Patients with Schizophrenia and Their Unaffected First-Degree Relatives / 신경정신의학

OBJECTIVES: This study aimed to identify the differences in the profiles of cognitive control deficits among schizophrenic patients and endophenotypes. METHODS: The study examined three groups: remitted patients with schizophrenia (n=54), unaffected first-degree relatives of the probands with schizophrenia (n=36), and a healthy control group (n=51), which were all matched for age, sex, and years of education. The AX version of the continuous performance test was used to examine cognitive control. The error rate, correct response times of each subset (AX, BX, AY, BY), and d′ as an indication of the accuracy sensitivity index were calculated. The psychopathology, intelligence, and psychomotor speed were also assessed. RESULTS: Patients with schizophrenia showed significantly poorer error rates and d′ in the AX and BX subsets than the others. They showed more delayed correct response times than the healthy control group in all subsets. The first-degree relatives also showed more delayed correct response times in the BX and AY subsets than the healthy control group, but were similar to the patients. CONCLUSION: These findings suggest that cognitive control is impaired in schizophrenia and endophynotypes possibly share this delayed information processing from the higher loading states of cognitive control.

Cognitive performance and psychosocial functioning in patients with bipolar disorder, unaffected siblings, and healthy controls

Objective: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. Methods: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. Results: Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. Conclusion: Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.

A Study of Neurological Soft Signs in Patients with Schizophrenia and Their Unaffected Siblings

OBJECTIVES: This study was conducted to investigate the possibility of neurological soft signs as an endophenotype for schizophrenia by examining neurological soft signs in patients, their unaffected siblings and normal comparison subjects. METHODS: The study sample consisted of 32 patients, 25 of their unaffected siblings and 30 normal comparison subjects. Neurological soft signs were evaluated using the Cambridge Neurological Inventory Part 2. soft sign assessment. RESULTS: The patients were significantly more impaired than normal comparison subjects (p = 0.047) on primitive reflex. The patients were significantly more impaired than siblings (p = 0.004) and normal comparison subjects (p = 0.021) on motor coordination. The siblings performed better on sensory integration than the patients (p = 0.020) and normal comparison subjects (p = 0.036). CONCLUSIONS: This study suggests that neurological soft signs might be a potential biomarker for schizophrenia, but might not be an endophenotype for schizophrenia.

Association between the Catechol-O-Methyltransferase (COMT) Val(158)Met Polymorphism and Alexithymia in Patients with Obsessive-Compulsive Disorder

PURPOSE: Alexithymia, defined as a deficit in the ability to recognize and describe one's own feelings, may be related to the development and maintenance of obsessive-compulsive symptoms. The aim of this study was to evaluate the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and alexithymia in patients with obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: We recruited 244 patients with OCD (169 males, 75 females). Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20), and genotyping of the COMT Val(158)Met polymorphism was evaluated. RESULTS: Patients with the COMT Val/Val genotype had significantly higher total and "difficulty identifying feelings" (DIF) subdimension scores than those with the Val/Met or Met/Met genotypes. Patients with the COMT Val/Val genotype had significantly higher "difficulty describing feelings" (DDF) subdimension scores than those with the COMT Val/Met genotype. However, there were no differences in the scores for the "externally oriented thinking" (EOT) subdimension among the three genotypes. CONCLUSION: These results indicate that the high-activity Val allele of the COMT Val(158)Met polymorphism is associated with increased alexithymic traits in patients with OCD. The present finding suggests that alexithymia is an endophenotype of OCD that is mediated by the COMT Val(158)Met polymorphism.

Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission

Objective:To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly.Methods:Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance.Results:For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001).Conclusion:Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.

Neuropsychological dysfunction in adults with early-onset obsessive-compulsive disorder: the search for a cognitive endophenotype

Objective: Evidence suggests that early-onset obsessive-compulsive disorder (OCD) is an etiologically distinct subtype of OCD. The objective of the present work was to search for neurocognitive endophenotypes of early-onset OCD based on assessments of attention, memory, and executive function in patients with the disorder and their unaffected siblings. Methods: We compared the performance of 40 adult patients with early-onset OCD, 40 of their unaffected siblings, and 40 unrelated healthy controls on a neuropsychological battery designed for this study. We searched for associations among test performance, demographic variables (age, sex and years of education) and clinical symptoms of early-onset OCD. Results: Patients performed significantly worse than healthy controls on the Tower of Hanoi, and the Stroop and Wisconsin tests, indicating impairments in planning, mental flexibility and inhibitory control. The performance of the unaffected first-degree siblings of patients with early-onset OCD on the Stroop and Wisconsin tests also differed from that of healthy controls. Symptom severity in early-onset OCD was strongly correlated with performance on the Tower of Hanoi. Conclusions: Our findings support the existence of specific executive function deficits in patients with early-onset OCD. Relatives presented an intermediate phenotype between patients and controls, suggesting that executive functions such as mental flexibility and response inhibition may be considered candidate endophenotypes of early-onset OCD. .

Endofenótipo da dislexia: hereditariedade, alterações de linguagem e influências do processamento fonológico e memória visual nas habilidades de leitura, escrita e matemática / Endophenotype of dyslexia: heredity, language changes and influences of phonological processing and visual memory skills in reading, writing and math

Os fatores genéticos e hereditários têm ganhado um foco especial como causa da dislexia, entretanto, há muito a ser estudado na busca de sua etiologia. Há vasta literatura associando o processamento fonológico ao aprendizado da leitura e escrita, porém pouco é investigado sobre a participação do processamento visual nas habilidades de leitura. Atualmente, a relação entre processamento fonológico e matemática tem sido apontada nas publicações científicas, sendo ainda pouco estudada, havendo necessidade de melhor compreensão entre a relação dessas habilidades, bem como as comorbidades entre dislexia e problemas na matemática. Este estudo teve como objetivo geral descrever o perfil endofenótipo dos sujeitos com dislexia referente à hereditariedade e influência do processamento fonológico e memória sequencial visual nas dificuldades da linguagem escrita e na matemática, no intuito de identificar semelhanças e diferenças no processamento da informação escrita entre indivíduos com dislexia e bons leitores. Participaram 35 indivíduos com o diagnóstico de dislexia e 46 bons leitores, de 8 a 13 anos e ambos os sexos. Nos dois grupos foram avaliadas as habilidades do processamento fonológico (consciência fonológica, acesso ao léxico e memória de trabalho fonológica), leitura de palavras, pseudopalavras, compreensão de texto, escrita e habilidades matemáticas. As habilidades do processamento fonológico e memória visual foram correlacionadas com a leitura, escrita e matemática nos dois grupos. Foi utilizado o Teste de Correlação de Pearson para correlacionar tais habilidades, e o Teste Qui-Quadrado e Teste U de Mann-Whitney para comparar o desempenho entre os grupos, adotando-se nível de significância de 5%. Encontrou-se que o histórico familial de problemas de aprendizagem esteve presente em mais da metade do grupo com dislexia, demonstrando que este é um importante fator de risco. Os indivíduos com dislexia apresentam pior...

Genetic and hereditarity factors have gained a special focus as the cause of dyslexia, however, there is much to be studied in the search for its etiology. There is extensive literature linking phonological processing to reading and writing learning, but the participation of visual processing in reading skills is little investigated. Currently, the relationship between phonological processing and mathematics has been identified in scientific publications, but still scarcely studied, there is need for better understanding the relationship between these skills as well as the comorbidities between dyslexia and problems in mathematics. This study aimed to describe the endophenotype profile of the subjects with dyslexia related to hereditarity and influence of phonological processing and visual sequential memory difficulties in written language and mathematics, in order to identify similarities and differences in written information processing between individuals with dyslexia and good readers. Participated in the study 35 diagnosed with dyslexia and 46 good readers, from 8 to 13 years old, both genders. Both groups were assessed the phonological processing skills (phonological awareness, lexical access and phonological working memory), words and pseudo words reading, reading comprehension, writing and math skills. The skills of phonological processing and visual memory were correlated with reading, writing and math in both groups. It was used the Pearson's Correlation Test to correlate these skills, and the Chi-square Test and Mann-Whitney Test to compare the performance between the groups, adopting a significance level of 5%. Family history of learning problems was present in more than half of the group with dyslexia, demonstrating that this is an important risk factor. Individuals with dyslexia performed worse in the phonological processing...

Endofenótipo da dislexia: hereditariedade, alterações de linguagem e influências do processamento fonológico e memória visual nas habilidades de leitura, escrita e matemática / Endophenotype of dyslexia: heredity, language changes and influences of phonological processing and visual memory skills in reading, writing and math

Os fatores genéticos e hereditários têm ganhado um foco especial como causa da dislexia, entretanto, há muito a ser estudado na busca de sua etiologia. Há vasta literatura associando o processamento fonológico ao aprendizado da leitura e escrita, porém pouco é investigado sobre a participação do processamento visual nas habilidades de leitura. Atualmente, a relação entre processamento fonológico e matemática tem sido apontada nas publicações científicas, sendo ainda pouco estudada, havendo necessidade de melhor compreensão entre a relação dessas habilidades, bem como as comorbidades entre dislexia e problemas na matemática. Este estudo teve como objetivo geral descrever o perfil endofenótipo dos sujeitos com dislexia referente à hereditariedade e influência do processamento fonológico e memória sequencial visual nas dificuldades da linguagem escrita e na matemática, no intuito de identificar semelhanças e diferenças no processamento da informação escrita entre indivíduos com dislexia e bons leitores. Participaram 35 indivíduos com o diagnóstico de dislexia e 46 bons leitores, de 8 a 13 anos e ambos os sexos. Nos dois grupos foram avaliadas as habilidades do processamento fonológico (consciência fonológica, acesso ao léxico e memória de trabalho fonológica), leitura de palavras, pseudopalavras, compreensão de texto, escrita e habilidades matemáticas. As habilidades do processamento fonológico e memória visual foram correlacionadas com a leitura, escrita e matemática nos dois grupos. Foi utilizado o Teste de Correlação de Pearson para correlacionar tais habilidades, e o Teste Qui-Quadrado e Teste U de Mann-Whitney para comparar o desempenho entre os grupos, adotando-se nível de significância de 5%. Encontrou-se que o histórico familial de problemas de aprendizagem esteve presente em mais da metade do grupo com dislexia, demonstrando que este é um importante fator de risco. Os indivíduos com dislexia apresentam pior...

Genetic and hereditarity factors have gained a special focus as the cause of dyslexia, however, there is much to be studied in the search for its etiology. There is extensive literature linking phonological processing to reading and writing learning, but the participation of visual processing in reading skills is little investigated. Currently, the relationship between phonological processing and mathematics has been identified in scientific publications, but still scarcely studied, there is need for better understanding the relationship between these skills as well as the comorbidities between dyslexia and problems in mathematics. This study aimed to describe the endophenotype profile of the subjects with dyslexia related to hereditarity and influence of phonological processing and visual sequential memory difficulties in written language and mathematics, in order to identify similarities and differences in written information processing between individuals with dyslexia and good readers. Participated in the study 35 diagnosed with dyslexia and 46 good readers, from 8 to 13 years old, both genders. Both groups were assessed the phonological processing skills (phonological awareness, lexical access and phonological working memory), words and pseudo words reading, reading comprehension, writing and math skills. The skills of phonological processing and visual memory were correlated with reading, writing and math in both groups. It was used the Pearson's Correlation Test to correlate these skills, and the Chi-square Test and Mann-Whitney Test to compare the performance between the groups, adopting a significance level of 5%. Family history of learning problems was present in more than half of the group with dyslexia, demonstrating that this is an important risk factor. Individuals with dyslexia performed worse in the phonological processing...

Neurocognitive Deficits in Patients with Schizophrenia and Unaffected First-Degree Relatives

OBJECTIVES: This study aimed to identify the differences and the profiles of cognitive deficits in remitted patients with schizophrenia and first-degree relatives of schizophrenic probands. METHODS: A total of 26 remitted states of schizophrenia patients were included in the study and the same number of unaffected first-degree relatives of schizophrenic probands and healthy controls were matched for age, sex, years of education. Cognitive function of all participants was measured by using the Digit span test, the Continuous performance test, the Rey auditory & visual learning test, the Complex figure test, the Verbal fluency test, the Wisconsin card sorting test and the Finger tapping test. The effects of subsyndromal symptomatology and general intelligence score were controlled. RESULTS: Schizophrenia patients' group showed more significant impairment than other groups in verbal memory (learning, immediate recall, delayed recall), visual memory (copy, immediate recall, delayed recall) and cognitive flexibility domains. The family group and the patient group commonly performed significantly worse than healthy controls in working memory and verbal fluency (category) tests. There were no differences in sustained attention, psychomotor performance. CONCLUSIONS: Our research shows that the deficit in working memory and verbal fluency could be strong candidates of endophenotypic marker in schizophrenia.

A control study of error-related negativity in internalizing mental disorders / 中华行为医学与脑科学杂志

Objective To investigate error-related negativity characteristics of patients with internalizing mental disorders and its diagnostic value.Methods Fifty-five patients met with DSM-Ⅳ anxiety or depression criteria were sampled from outpatients and inpatients,and 20 normal adults were selected as control group.With Eriksen and Simon tasks as evoked stimuli,error-related negativities of each participant were acquired using Canada Stellate-64 channel EEG/ERP Instrument and BESA5.2 software,and the data of general information,clinical symptoms,reaction time,and error rate were collected.Results (1) Correct reaction time ((377.5±98.8) ms)and errors reaction time ((337.3±96.6)ms) of patient group were significantly longer than those of control group ((288.5±105.9)ms and (281.9±94.3)ms) on the Eriksen task and Simon task,and there were no significantly group differences on other indicators (P＞0.05).(2) ERN amplitudes at 6 sities (Fz =(4.97±5.74) μV,F3 =(5.50±4.59) μV,F4 =(6.26±6.79) μV,Cz =(4.74±5.51) μV,C3 =(5.44±4.8) μV,C4 =(5.50± 5.28) μV) of patients group were significantly greater than those of control group ((1.17± 1.47)μV,(2.22±3.95) μV,(3.40±2.55)μV,(2.28± 1.41) μV,(3.05±2.47) μV,(3.16±2.51) μV) on the Eriksen task.ERN amplitudes at Fz((5.43±6.61) μV) and F4((6.00±5.50)μV) of patient group were significantly were greater than those of control group ((2.05 ±2.34) μV,(3.09±2.86)μV) on the Simon task,and there were no significantly group differences on the ERN amplitudes at other sites (P＞0.05).(3) ERN latencies ((87.6±34.4) ms and (84.9±34.8) ms) of patient group at Fz and F4 were significantly longer than control group ((54.0±46.5) ms and (36.3±42.4)ms) on the Simon task,and there were no significantly group differences on the ERN latencies at other sites (P＞0.05).Conclusion The increased error related potentials suggest that patients with internalizing mental disorders has an internal error monitoring defects,and ERN might be a useful endophenotype for internalizing mental disorders.

Neuropsychological and Behavioral Profiles in Attention-Deficit Hyperactivity Disorder Children of Parents with a History of Mood Disorders: A Pilot Study

OBJECTIVE: We aimed to investigate the neurocognitive and behavioral endophenotypes of premorbid mood disorder. We compared intelligence, neuropsychological functioning, and behavioral problems among three groups: 1) a high-risk group [attention-deficit hyperactivity disorder (ADHD) children of parents with a history of a mood disorder], 2) a low-risk group (ADHD children of parents without a history of a mood disorder), and 3) normal comparison subjects. METHODS: We used the Korean Educational Development Institute Wechsler Intelligence Scale for Children-Revised (KEDI-WISC-R), the Stroop Color Word Interference Test (Stroop), the Wisconsin Card Sorting Test (WCST), and the Rey-Osterrieth Complex Figure Test (RCFT) as neurocognitive measures, and we used the Child Behavior Checklist (CBCL) as a behavioral measure. Performance on these neuropsychological tests and score on the CBCL of 18 high-risk children were compared to those of 20 low-risk children and 24 healthy children. We also assessed the children's current mood state and familial functioning to control for the confounding effects of these variables. RESULTS: Compared to low-risk and healthy children, high-risk children were impaired on the Picture Completion and Stroop Word subtest and showed higher scores on the CBCL subscales representing internalizing symptoms. These significant group differences persisted even after adjustment for the children's current mood state and familial functioning. CONCLUSION: Neuropsychological deficits in the offspring of parents with a mood disorder may be associated with the current mood state rather than with innate characteristics, while their internalizing symptoms may partially stem from innate characteristics that are endophenotypes of a premorbid mood disorder.