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.

[Utility of the Wender-Utah rating scale and the checklists for the diagnosis of familial attention deficit hyperactivity disorder in adults. Convergent and concurrent validities]. / Utilidad de la escala Wender-Utah y de las escalas de sintomas para el diagnostico del trastorno por deficit de atencion/hiperactividad familiar en adultos. Validez convergente y concurrente.

INTRODUCTION: Standard questionnaires to characterize familial attention deficit hyperactivity disorder (ADHD) of adults have been studied in some studies. AIM: To observe convergent and concurrent validity of four standard rating scales to quantify the familial ADHD symptoms of adults. PATIENTS AND METHODS: The sample was constituted by the 392 adults; aged 18 through 84 years, belonging to 141 Antioquian families with multiple ADHD affected members, who fulfilled by self-report the Wender-Utah Rating Scale and the ADHD checklist; and, beside, answered a questionnaire asking for current and past ADHD symptoms, in a neurological interview. Correlation analyses were done. Sensitivity and specificity for ADHD diagnosis were also determined. RESULTS: Significant and over 0.6 correlations were observed between scales that explored past ADHD symptoms. Distant cut-off points for 90% sensitivity and specificity were observed for all questionnaires. The best LR+ (12.15) was found for the report of 5 or more past hyperactivity-impulsivity symptoms; follow by the report of 7 or more past ADHD symptoms (6.92). CONCLUSIONS: Cut-off points should be taken with caution when these rating scales were used for adult ADHD screening. Psychometric properties do not allow using these scales as substitution of structured clinical interview for the gold standard ADHD diagnosis in adults.

Utilidad de la escala Wender-Utah y de las escalas de síntomas para el diagnóstico del trastorno por déficit de atención/hiperactividad familiar en adultos. Validez convergente y concurrente / Utility of the Wender-Utah Rating Scale and the checklists for the diagnosis of familial attention deficit hyperactivity disorder in adults. Convergent and concurrent validities

Introducción. El uso de los cuestionarios para caracterizar el trastorno por déficit de atención/hiperactividad (TDAH) familiar del adulto ha sido estudiado por múltiples autores. Objetivo. Observar la validez convergente y concurrente de cuatro instrumentos estandarizados para cuantificar los síntomas del TDAH familiar del adulto. Pacientes y métodos. La muestra estuvo constituida por los 392 adultos de 18 a 84 años de edad, pertenecientes a 141 familias antioqueñas con múltiples afectados de TDAH, quienes respondieron mediante autoinforme los cuestionarios retrospectivos de Wender-Utah y la lista de síntomas de TDAH; además, contestaron en la entrevista neurológica el cuestionario del número de síntomas de TDAH presentados en el pasado y los síntomas actuales. Se hizo análisis de correlación de las puntuaciones y se calculó la sensibilidad y especificidad de los instrumentos para el diagnóstico de TDAH. Resultados. Se observaron correlaciones significativas y mayores de 0,6 entre los cuestionarios que exploraron síntomas de TDAH del pasado. Los cuestionarios tuvieron puntos de corte distantes para la sensibilidad y especificidad del 90%. La mejor razón de verosimilitud positiva (12,15) se encontró para el informe de cinco o más síntomas de hiperactividadimpulsividad en el pasado, seguido del informe de siete o más síntomas de TDAH en el pasado (6,92). Conclusiones. Para el uso de cualquiera de estos instrumentos en el rastreo de adultos con sospecha de TDAH, se debe ser cauteloso con los puntos de corte. El comportamiento psicométrico no permite su utilización en reemplazo de la entrevista estructurada como técnica de referencia del diagnóstico de TDAH del adulto (AU)

Introduction. Standard questionnaires to characterize familial attention deficit hyperactivity disorder (ADHD) of adults have been studied in some studies. Aim. To observe convergent and concurrent validity of four standard rating scales to quantify the familial ADHD symptoms of adults. Patients and methods. The sample was constituted by the 392 adults; aged 18 through 84 years, belonging to 141 Antioquian families with multiple ADHD affected members, who fulfilled by self-report the Wender-Utah Rating Scale and the ADHD checklist; and, beside, answered a questionnaire asking for current and past ADHD symptoms, in a neurological interview. Correlation analyses were done. Sensitivity and specificity for ADHD diagnosis were also determined. Results. Significant and over 0.6 correlations were observed between scales that explored past ADHD symptoms. Distant cut-off points for 90% sensitivity and specificity were observed for all questionnaires. The best LR+ (12.15) was found for the report of 5 or more past hyperactivity-impulsivity symptoms; follow by the report of 7 or more past ADHD symptoms (6.92). Conclusions. Cut-off points should be taken with caution when these rating scales were used for adult ADHD screening. Psychometric properties do not allow using these scales as substitution of structured clinical interview for the gold standard ADHD diagnosis in adults (AU)

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.