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Neuroanatomic, epigenetic, and genetic differences in monozygotic twins discordant for Attention Deficit Hyperactivity Disorder

The study of monozygotic twins discordant for Attention Deficit Hyperactivity Disorder can elucidate mechanisms that contribute to the disorder, which affects around 7% of children. First, using in vivo neuroanatomic imaging on 14 pairs of monozygotic twins (mean age 9.7, standard deviation 1.9 year...

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Detalles Bibliográficos
Autores principales: Chen, Yun-Ching, Sudre, Gustavo, Sharp, Wendy, Donovan, Frank, Chandrasekharappa, Settara C., Hansen, Nancy, Elnitski, Laura, Shaw, Philip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914518/
https://www.ncbi.nlm.nih.gov/pubmed/28322272
http://dx.doi.org/10.1038/mp.2017.45
Descripción
Sumario:The study of monozygotic twins discordant for Attention Deficit Hyperactivity Disorder can elucidate mechanisms that contribute to the disorder, which affects around 7% of children. First, using in vivo neuroanatomic imaging on 14 pairs of monozygotic twins (mean age 9.7, standard deviation 1.9 years), we find that discordance for the disorder is mirrored by differing dimensions of deep brain structures (the striatum and cerebellum), but not the cerebral cortex. Next, using whole blood DNA from the same twins, we find a significant enrichment of epigenetic differences in genes expressed in these ‘discordant’ brain structures. Specifically, there is differential methylation of probes lying in the shore and shelf and enhancer regions of striatal and cerebellar genes. Notably, gene sets pertaining to the cerebral cortex (which did not differ in volume between affected and unaffected twins) were not enriched by differentially methylated probes. Genotypic differences between the twin pairs – such as copy number and rare, single nucleotide variants- did not contribute to phenotypic discordance. Pathway analyses of the genes implicated by the most differentially methylated probes implicated GABA, dopamine and serotonin neurotransmitter systems. The study illustrates how neuroimaging can help guide the search for epigenomic mechanisms in neurodevelopmental disorders.