Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders

Exposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, n...

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Published in:Translational psychiatry 2016-11, Vol.6 (11), p.e943-e943
Main Authors: Luoni, A, Massart, R, Nieratschker, V, Nemoda, Z, Blasi, G, Gilles, M, Witt, S H, Suderman, M J, Suomi, S J, Porcelli, A, Rizzo, G, Fazio, L, Torretta, S, Rampino, A, Berry, A, Gass, P, Cirulli, F, Rietschel, M, Bertolino, A, Deuschle, M, Szyf, M, Riva, M A
Format: Article
Language:English
Subjects:
Animals
Ankyrins - genetics
Bipolar Disorder - genetics
Cohort Studies
Disease Models, Animal
DNA Methylation
Female
Genetic Markers - genetics
Genetic Predisposition to Disease - genetics
Genome-Wide Association Study
Humans
Infant, Newborn
Life Change Events
Macaca mulatta
Male
Memory, Short-Term
Mental Disorders - genetics
Original
Phenotype
Pregnancy
Prenatal Exposure Delayed Effects - genetics
Promoter Regions, Genetic - genetics
Rats
Schizophrenia - genetics
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Summary:Exposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, non-human primates and humans, all characterized by ELS. We identified Ankyrin-3 (Ank3), a scaffolding protein with a strong genetic association for psychiatric disorders, as a gene persistently affected by stress exposure. In rats, Ank3 methylation and mRNA changes displayed a specific temporal profile during the postnatal development. Moreover, exposure to prenatal stress altered the interaction of ankyrin-G, the protein encoded by Ank3 enriched in the post-synaptic compartment, with PSD95. Notably, to model in humans a gene by early stress interplay on brain phenotypes during cognitive performance, we demonstrated an interaction between functional variation in Ank3 gene and obstetric complications on working memory in healthy adult subjects. Our data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders.
ISSN:2158-3188
2158-3188
DOI:10.1038/tp.2016.211