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Attention deficits, childhood malnutrition, cognition, DNA methylation, epigenetics, prefrontal cortex
Abstract:
BACKGROUND: Early childhood malnutrition affects 113 million children
worldwide, impacting health and increasing vulnerability for cognitive
and behavioral disorders later in life. Molecular signatures after
childhood malnutrition, including the potential for intergenerational
transmission, remain unexplored.
METHODS: We surveyed blood DNA methylomes (similar to 483,000 individual
CpG sites) in 168 subjects across two generations, including 50
generation 1 individuals hospitalized during the first year of life for
moderate to severe protein-energy malnutrition, then followed up to 48
years in the Barbados Nutrition Study. Attention deficits and cognitive
performance were evaluated with the Connors Adult Attention Rating Scale
and Wechsler Abbreviated Scale of Intelligence. Expression of
nutrition-sensitive genes was explored by quantitative reverse
transcriptase polymerase chain reaction in rat prefrontal cortex.
RESULTS: We identified 134 nutrition-sensitive, differentially
methylated genomic regions, with most (87%) specific for generation 1.
Multiple neuropsychiatric risk genes, including COMT, IFNG, MIR200B,
SYNGAP1, and VIPR2 showed associations of specific methyl-CpGs with
attention and IQ. IFNG expression was decreased in prefrontal cortex of
rats showing attention deficits after developmental malnutrition.
CONCLUSIONS: Early childhood malnutrition entails long-lasting
epigenetic signatures associated with liability for attention and
cognition, and limited potential for intergenerational transmission.
