RESUMO
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.
RESUMO
OBJECTIVE: To study the association of dementia with apolipoprotein E-e4 (APOE-e4) and its interaction with age in a nonagenarian Costa Rican group (N-sample) and a general elderly contrast group (GE-sample). METHODS: In both case-control studies, participants were cognitively intact or diagnosed with dementia. The N-sample (N = 112) was at least age 90 years; the GE-sample (N = 98) was at least age 65 years. RESULTS: Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93 years) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. CONCLUSIONS: The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging.