Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate.

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association.

Modelo multidimensional de la conducta en una muestra de niños usando cuestionarios normalizados para padres y maestros / Multidimensional model of the behavior from a children simple using standardized questionnaires for parents and teachers

Los análisis de factores de la versión hispana de la (Behavioral Assessment System for Childre, BASC) corroboran el modelo multidimensional de la conducta humna. El objetivo del presente estudio consiste en analizar la estructura dimensional de la versión colombiana del BASC. Para ello se seleccionó una muestra aleatoria de 1.176 niños de 6 a 11 años escolarizados de la ciudad de Manizales (Colombia). A los padres y maestros se les administró los cuestionarios correspondientes del BASC. Resultados: La escala de padres tuvo una estructura de dos factores: clínico y de adaptación, con una explicación de la varianza del 64% y con un índice de adecuación KMO=0,87. En el cuestionario de maestros, el factor clínico se dividió en conductas de exteriorización (factor 1) y conductas de interiorización (factor 3) y la dimensión de adaptación apareció como el factor 2 (75,2% de la varianza). La medida de adecuación fue de KMO=0,90

Factor analyses of Behavioral Assessment System for Children (BASC) parents´ and teachers´ questionnaires have supported the multidimensional theory of human behavior. The goal of this study was to analyze the dimensional structure of the BASC parents and teachers Spanish version questionnaires. In order to do this, a randomized sample of 1.176 children aged 6 o11 years old, from the schools of Manizales City (Colombia), was selected. BASC parents and teachers questionnaires were administered to the participants. The results show that BASC parents had two dimensions: clinical and adaptive, KMO= 0,87, which explained 64% of the variance. BASC teachers had two clinical dimensions: externalizing (factor 1) and internalizing (factor 3), and he adaptive dimension was the factor 2 (75,2% of the variance). KMO was 0,90

Alteraciones cognitivas en adolescentes infractores con trastorno disocial de diversos niveles de gravedad / Cognitive impairment of adolescent offenders with conduct disorder of different severity levels

Se ha postulado que las alteraciones cognitivas en los jóvenes con trastorno disocial de la conducta (TDC) pudieran relacionarse con gravedad de los síntomas. Se buscó determinar las diferencias entre grupos de adolescentes varones infractores [AI] con TDC grave o leve con un grupo de adolescentes no infractores [ANI]- sin TDC. La muestra fue de 228 adolescentes; 117 eran AI con TDC y 111 ANI sin TDC. Se aplicó una batería neuropsicológica breve y como patrón de oro una entrevista psiquiátrica estructurada. Se identificaron diferencias estadísticamente significativas en comportamiento verbal entre los ANI y ambos grupos de AI con TDC. Al compara los dos grupos de AI se observa que los AI-TDC grave presentan una menor capacidad de evocación inmediata de información verbal y más lentitud para la denominación de colores (p<0,05). En conclusión, se corrobora los hallazgos de otras investigaciones acerca de deficientes habilidades verbales de los AI con TDC, además se observan deficiencias cognitivas en memoria y velocidad del procesamiento verbal/visual en los AI-TDC grave, lo cual ameritaría futuros estudios con diseños experimentales

Several cognitive impairments related with conduct disorder (CD) severity have been reported. The present study attempted to determine the differences between groups of adolescent offenders (AO) with mild and sever CD and adolescent non-groups of adolescent offenders (AO= with mild and severe CD and adolescent non-offenders (ANO) without CD. The sample was composed of 228 participants aged 12 to 16 years old, grouped in 117 AOs belonging to an education institution for young offenders (23 were classified as mild CD and 94 as sever CD) according to DSM-IV-TR symptoms and 111 ANOs form regular education institutions. All participants live in the metropolitan area of Medellin city and belong to low socioeconomic strata. Statistical significant differences were found on verbal behavior tasks, when ANO and AO groups were compared. When the two groups of AOS were compared, the AO with severe CD exhibited significant lesser capacity of immediate verbal information recall and slower speed for color naming (p<0.005). In our conclusions, findings that report significant lower verbal skills were confirmed, and very specific cognitive deficiencies in memory and verbal/visual speed processing were found in the AOs with sever CD group, which will oblige to design more rigorous experimental studies

The role of neuropsychologic tests in the diagnosis of attention deficit hyperactivity disorder.

Attention, memory, executive function, language, and visual-motor skills were evaluated in a sample of 621 children, 6 to 11 years old, to assess the discriminant validity of neuropsychologic testing. Attention deficit hyperactivity disorder cases (249) and controls (372) were identified and tested. Analysis of covariance, nonparametric comparison tests, effect sizes, discriminant function, factor analyses, and receiver-operator characteristics curve analyses were used to establish the best diagnostic cutoff points for each variable. Statistically significant differences were found on cognitive effort, auditory skills, continuous performance test, working memory, visual-motor skills, verbal comprehension, and executive function measures (P < 0.05); however, the effect of group sizes was low to modest (0.24 to 0.54). Receiver-operator characteristics curve analysis showed modest sensitivity and low specificity, demonstrating that an important proportion of the variance in test scores was overlapping. Factor analysis of neuropsychologic testing results revealed a structure of six factors each for attention deficit hyperactivity disorder, control, and combined samples. The latent variables produced one discriminant function with a total correct classification accuracy of 61.9%. Neuropsychologic tests should be used as Attention Deficit Hyperactivity Disorder diagnostic tools with caution, but they hold promise for identifying core cognitive deficits and processes that can aid prevention and intervention.

Environmental influences that affect attention deficit/hyperactivity disorder: study of a genetic isolate.

Three independent complex segregation analyses found that the cause of Attention Deficit/Hyperactivity Disorder (ADHD) was the presence of major genes interacting with environmental influences. In order to identify potential environmental risk factors for ADHD in the Paisa community--a very well described, genetically isolated group--we randomly selected a sample of 486 children between 6 and 11 years of age. This group included 200 children with ADHD (149 males and 51 females) and 286 healthy controls (135 males and 151 females). The ADHD DSM-IV diagnosis was obtained using the DICA and BASC evaluation instruments, and the children's mothers or grandmothers filled out a questionnaire on each child's exposure to prenatal, neonatal, and early childhood risk factors. The data were analyzed using cross tabulation and stepwise logistic multiple-regression analyses. Cross tabulation associated ADHD with a variety of factors, including miscarriage symptoms, premature delivery symptoms, maternal respiratory viral infection, moderate to severe physical illness in the mother during gestation, prenatal cigarette and alcohol exposure, neonatal seizures, asphyxia or anoxia, severe neonatal illness, mild speech retardation, moderate brain injury, and febrile seizures (odds ratio >or= 2, P < 0.05). Stepwise logistic multiple-regression analysis also uncovered a block of variables, including male gender, maternal illnesses, prenatal alcohol exposure, mild speech retardation, febrile seizures, and moderate brain injury (odds ratio >or= 2.0, P < 0.05). Future studies on the risk of developing ADHD must include these environmental factors as covariates.

Screening for conduct disorder in an adolescent male sample from Colombia.

This study assessed the validity, reliability, and utility of a screening measure for detecting the signs or symptoms of Conduct Disorder in male adolescents from schools in Medellín, Colombia. A first study examined the differences between 70 male offender adolescents (aged 12-16 years) attending alternative education institutions, and 68 (sex, age, and socioeconomic status (SES)-matched) adolescent controls attending regular schools. A CD checklist (CD-CL) was constructed to be used by mothers (CD-CL-M) and for self-report by adolescents (CD-CL-SR). The validity of the screener for CD diagnosis was supported by significant differences between groups (ANOVA, p<.001). The CD-CL-SR had better sensitivity/specificity with a diagnostic cut-off point of 5 (sensitivity=95.3% and specificity=90.5%) than the CD-CL-M. A second study used the CD-CLSR with a random sample of 190 male adolescents (aged 12 to 16 years) from schools of low, middle and high SES. Reliability as assessed by Cronbach's alpha was 0.86. An epidemiological cut point of 5 classified 35.5% of the adolescents assessed as probable CD cases. A psychometric cut point at T score>59 (85th percentile) estimated 16.8% of the sample as probable CD cases. A psychometric cut point at T score>64 (90th percentile) revealed that 10.5% of the sample would be severe CD cases. Some significant differences (p<0.001) in proportions of CD adolescents were found between age and SES groups. It was concluded that such a high frequency of conduct problems in adolescence argues for the need for preventive programs in Colombian schools.

Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families.

OBJECTIVE: Eighteen extended multigenerational families were recruited from the genetically isolated Paisa community in Colombia to conduct genetic studies of attention-deficit/hyperactivity disorder (ADHD). This report describes the inclusion strategy and clinical features of participants to facilitate comparisons with other data sets. METHOD: Families were selected through a fixed-sampling scheme beginning with child probands referred for clinical evaluation for ADHD. Direct structured psychiatric interviews were conducted with 433 informative individuals, including 92 children aged 4 to 11, 57 adolescents aged 12 to 17, and 284 adults. Best estimate ADHD diagnoses were established for each informative pedigree member. RESULTS: These families contained a high proportion of individuals affected with ADHD (32.8%), which was highly comorbid with conduct disorder (50%; odds ratio 11.5, 95% confidence interval = 6.4-20.9), oppositional defiant disorder (25.4%; odds ratio 2.7, confidence interval = 1.5-4.8), and associated conditions including nicotine dependence and alcohol abuse and/or dependence. CONCLUSIONS: ADHD in these extended Paisa families is highly comorbid with conduct and oppositional defiant disorders. This pattern of comorbidity, as well as the large dense pedigrees of the sample, suggests that it will be particularly useful for molecular genetic studies that are currently under way.