Subject(s)
Adolescent Psychiatry/trends , Child Psychiatry/trends , Adolescent , Brazil , Child , HumansSubject(s)
Humans , Child , Adolescent , Child Psychiatry/trends , Adolescent Psychiatry/trends , BrazilABSTRACT
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.
Subject(s)
Attention Deficit Disorder with Hyperactivity/ethnology , Attention Deficit Disorder with Hyperactivity/genetics , Intergenerational Relations , Aged , Alcoholism/diagnosis , Alcoholism/ethnology , Alcoholism/genetics , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit and Disruptive Behavior Disorders/diagnosis , Attention Deficit and Disruptive Behavior Disorders/ethnology , Attention Deficit and Disruptive Behavior Disorders/genetics , Catchment Area, Health , Colombia/epidemiology , Comorbidity , Humans , Male , Middle Aged , Pedigree , Sampling Studies , Tobacco Use Disorder/diagnosis , Tobacco Use Disorder/ethnology , Tobacco Use Disorder/geneticsABSTRACT
Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is the most common behavioral disorder of childhood. Twin, adoption, segregation, association, and linkage studies have confirmed that genetics plays a major role in conferring susceptibility to ADHD. We applied model-based and model-free linkage analyses, as well as the pedigree disequilibrium test, to the results of a genomewide scan of extended and multigenerational families with ADHD from a genetic isolate. In these families, ADHD is highly comorbid with conduct and oppositional defiant disorders, as well as with alcohol and tobacco dependence. We found evidence of linkage to markers at chromosomes 4q13.2, 5q33.3, 8q11.23, 11q22, and 17p11 in individual families. Fine mapping applied to these regions resulted in significant linkage in the combined families at chromosomes 4q13.2 (two-point allele-sharing LOD score from LODPAL = 4.44 at D4S3248), 5q33.3 (two-point allele-sharing LOD score from LODPAL = 8.22 at D5S490), 11q22 (two-point allele-sharing LOD score from LODPAL = 5.77 at D11S1998; multipoint nonparametric linkage [NPL]-log[P value] = 5.49 at approximately 128 cM), and 17p11 (multipoint NPL-log [P value] >12 at approximately 12 cM; multipoint maximum location score 2.48 [alpha = 0.10] at approximately 12 cM; two-point allele-sharing LOD score from LODPAL = 3.73 at D17S1159). Additionally, suggestive linkage was found at chromosome 8q11.23 (combined two-point NPL-log [P value] >3.0 at D8S2332). Several of these regions are novel (4q13.2, 5q33.3, and 8q11.23), whereas others replicate already-published loci (11q22 and 17p11). The concordance between results from different analytical methods of linkage and the replication of data between two independent studies suggest that these loci truly harbor ADHD susceptibility genes.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Genetic Linkage/genetics , Genome, Human , Haplotypes/genetics , Chromosome Mapping , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 4/genetics , Chromosomes, Human, Pair 5/genetics , Colombia , Humans , Lod Score , PedigreeABSTRACT
La prevalencia del trastorno por déficit de atención, cuando se utilizan instrumentos de diagnóstico epidemiológico y de aplicación a padres de niños paìsas, puede llegar al 16.1-18/100; estas cifras han sido criticadas por apoyarse en una sola fuente de información. El objetivo del estudio fue establecer la prevalencia del trastorno en una comunidad paisa usando multiples métodos para su diagnóstico. Se seleccionó de manera aleatoria una muestra de 341 niños y adolescentes de 4 a 17 años, 184 niños y 157 niñas de los colegios de la ciudad de Manizales. Se estratificaron en dos niveles socioeconómicos. Para el diagnóstico se utilizaron diversos cuestionarios, destinados a padres y maestros para la evaluación de la conducta de los niños y los adolescentes, previamente estandarizados en la población paisa. El diagnóstico se confirmó mediante una entrevista neurológica y psiquiátrica semiestructurada, se revisaron las historicas clínicas y se hizo una evaluación clínica neurológica y psiquiátrica cuando fue necesario. El análisis preliminar de los datos obtenidos, muestra que la prevalencia de la enfermedad y de acuerdo a los criterios de DSM IV, fue del 17.1/100. La distribución según tipos fue: combinado, inatento e hiperactivo-impulsivo. La prevalencia de la enfermedad en la comunidad paisa, según estos estudios es más alta que la informada en estudios de otras poblaciones
Subject(s)
Attention Deficit and Disruptive Behavior Disorders , ColombiaABSTRACT
Há um volume crescente de evidências provenientes da fenomenologia clìnica, incluindo disturbios associados, visualizaçäo do cérebro e estudos neurofarmacológicos, ligando a sìndrome psiquiátrica clássica do distúrbio obsessivo-compulsivo (DOC) a disfunçöes dos glânglios basais e ao sistema serotonìnico. Atualmente, o DOC é a sìndrome psiquiátrica com maior probabilidade de ser originária de uma disfunçäo neurológica especìfica, o que é corroborado por um modelo animal extremamente convincente. Acredita-se que a disfunçäo nos gânglios basais e na alça talâmica cortical frontal produziria os sintomas "positivos" de excesso de preocupaçäo com a higiene pessoal, detalhismo e ambivalência que säo caracterìsticos do DCO. Talvez os dados mais intrigantes sejam os resultados preliminares de ensaios clìnicos, nos quais vários outros comportamentos anormais assemelhados ao excesso de cuidados com a higiene, tanto em animais quanto em humanos, podem estar relacionados ao DOC. Uma perspectiva etológica é sugerida
Subject(s)
Basal Ganglia/physiopathology , Obsessive-Compulsive Disorder/etiology , Clomipramine/therapeutic use , Desipramine/therapeutic use , Nail Biting/therapy , Serotonin Antagonists/therapeutic use , Trichotillomania/drug therapyABSTRACT
Ha um volume crescente de evidencias provenientes da fenomenologia clinica, incluindo disturbios associados, visualizacao do cerebro e estudos neurofarmacologicos, ligando a sindrome psiquiatrica classica do disturbio obsessivo-compulsivo (DOC) a disfuncoes dos ganglios basais e ao sistema serotoninico. Atualmente, o DOC e a sindrome psiquiatrica com maior probabilidade de ser originaria de uma disfuncao neurologica especifica, o que e corroborado por um modelo animal extremamente convincente. Acredita-se que a disfuncao nos ganglios basais e na alca talamica cortical frontal produziria os sintomas 'positivos' de excesso de preocupacao com a higiene pessoal, detalhismo e ambivalencia que sao caracteristicos do DCO. Talvez os dados mais intrigantes sejam os resultados preliminares de ensaios clinicos, nos quais varios outros comportamentos anormais assemelhados ao excesso de cuidados com a higiene, tanto em animais quanto em humanos, podem estar relacionados ao DOC. Uma perspectiva etologica e sugerida.