RESUMO
OBJECTIVE: Autism spectrum disorders (ASDs) are highly heritable neurodevelopmental disorders that onset clinically during the first years of life. ASD risk biomarkers expressed early in life could significantly impact diagnosis and treatment, but no transcriptome-wide biomarker classifiers derived from fresh blood samples from children with autism have yet emerged. METHOD: Using a community-based, prospective, longitudinal method, we identified 60 infants and toddlers at risk for ASDs (autistic disorder and pervasive developmental disorder), 34 at-risk for language delay, 17 at-risk for global developmental delay, and 68 typically developing comparison children. Diagnoses were confirmed via longitudinal follow-up. Each child's mRNA expression profile in peripheral blood mononuclear cells was determined by microarray. RESULTS: Potential ASD biomarkers were discovered in one-half of the sample and used to build a classifier, with high diagnostic accuracy in the remaining half of the sample. CONCLUSIONS: The mRNA expression abnormalities reliably observed in peripheral blood mononuclear cells, which are safely and easily assayed in infants, offer the first potential peripheral blood-based, early biomarker panel of risk for autism in infants and toddlers. Future work should verify these biomarkers and evaluate whether they may also serve as indirect indices of deviant molecular neural mechanisms in autism.
Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Leucócitos Mononucleares/metabolismo , Transcriptoma/genética , Transtornos Globais do Desenvolvimento Infantil/sangue , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Pré-Escolar , Estudos Transversais , Sondas de DNA/genética , Feminino , Perfilação da Expressão Gênica , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Humanos , Lactente , Transtornos do Desenvolvimento da Linguagem/sangue , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/genética , Estudos Longitudinais , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Estudos Prospectivos , RNA Mensageiro/genética , Valores de ReferênciaRESUMO
OBJECTIVES: To determine the feasibility of implementing a broadband screen at the 1-year check-up to detect cases of autism spectrum disorders (ASD), language delay (LD), and developmental delay (DD). STUDY DESIGN: The Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist was distributed at every 1-year pediatric check-up; 137 pediatricians and 225 infants participated. Screens were scored immediately, and failures referred for further evaluation. RESULTS: Pediatricians screened 10 479 infants at the 1-year check-up; 184 infants who failed the screen were evaluated and tracked. To date, 32 infants received a provisional or final diagnosis of ASD, 56 of LD, nine of DD, and 36 of "other." Five infants who initially tested positive for ASD no longer met criteria at follow-up. The remainder of the sample was false positive results. Positive predictive value was estimated to be .75. CONCLUSIONS: The 1-Year Well-Baby Check-Up Approach shows promise as a simple mechanism to detect cases of ASD, LD, and DD at 1 year. This procedure offers an alternative to the baby sibling design as a mechanism to study autism prospectively, the results of which will enrich our understanding of autism at an early age.