title: DNA Methylation Signatures of Early Childhood Malnutrition Associated With Impairments in Attention and Cognition.
abstract: 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.
  
  
  
  We surveyed blood DNA methylomes (~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.
  
  
  
  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.
  
  
  
  Early childhood malnutrition entails long-lasting epigenetic signatures associated with liability for attention and cognition, and limited potential for intergenerational transmission.
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Cyril J
authors.initials: CJ
authors.lastname: Peter
authors.affiliation: The Chester M. Pierce, MD Division of Global Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Fischer
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Marija
authors.initials: M
authors.lastname: Kundakovic
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Paras
authors.initials: P
authors.lastname: Garg
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Max Planck Institute for Psychiatry, Munich, Germany.
authors.forename: Mira
authors.initials: M
authors.lastname: Jakovcevski
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Aslihan
authors.initials: A
authors.lastname: Dincer
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Amaral
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School, Shrewsbury, Massachusetts; Department of Neurology, University of Massachusetts Medical School, Shrewsbury, Massachusetts; Department of Clinical Pathology, University of Massachusetts Medical School, Shrewsbury, Massachusetts.
authors.forename: Edward I
authors.initials: EI
authors.lastname: Ginns
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Shrewsbury, Massachusetts.
authors.forename: Marzena
authors.initials: M
authors.lastname: Galdzicka
authors.affiliation: Barbados Nutrition Study, Bridgetown, Barbados.
authors.forename: Cyralene P
authors.initials: CP
authors.lastname: Bryce
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Chana
authors.initials: C
authors.lastname: Ratner
authors.affiliation: Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Deborah P
authors.initials: DP
authors.lastname: Waber
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, Maine.
authors.forename: David
authors.initials: D
authors.lastname: Mokler
authors.affiliation: Barbados Nutrition Study, Bridgetown, Barbados.
authors.forename: Gayle
authors.initials: G
authors.lastname: Medford
authors.affiliation: Department of Psychology, Columbia University, New York, New York.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Champagne
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rosene
authors.affiliation: Department of Psychology, University of New Hampshire, Durham, New Hampshire.
authors.forename: Jill A
authors.initials: JA
authors.lastname: McGaughy
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sharp
authors.affiliation: The Chester M. Pierce, MD Division of Global Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors.forename: Janina R
authors.initials: JR
authors.lastname: Galler
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: schahram.akbarian@mssm.edu.
authors.forename: Schahram
authors.initials: S
authors.lastname: Akbarian
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology* / Q000235:genetics; D001460:Barbados; D001522:Behavior, Animal; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000235:genetics; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009749:Nutrition Surveys; D017397:Prefrontal Cortex / Q000378:metabolism*; D011502:Protein-Energy Malnutrition / Q000150:complications* / Q000235:genetics; D051381:Rats; D055815:Young Adult
keywords: Attention deficits; Childhood malnutrition; Cognition; DNA methylation; Epigenetics; Prefrontal cortex