DNA Methylation at the DAT Promoter and Risk for Psychopathology: Intergenerational Transmission between School-Age Youths and Their Parents in a Community Sample

Frontiers in Psychiatry

Walter Adriani¹  Claudio D’Addario²  Giulia Ballarotto³  Eleonora Marzilli³  Renata Tambelli³  Silvia Cimino³  Esterina Pascale⁴  Luca Cerniglia⁶ 

[1]Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy

[2]Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

[3]Department of Dynamic and Clinical Psychology, Sapienza University of Rome, Rome, Italy

[4]Department of Medical Surgical Sciences and Biotechnology, Sapienza University of Rome, Rome, Italy

[5]Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy

[6]Faculty of Psychology, International Telematic University Uninettuno, Rome, Italy

关键词: epigenetics;    DAT;    5′-untranslated region;    variable number of tandem repeats polymorphism;    genotype;    methylation;   

DOI  :  10.3389/fpsyt.2017.00303

来源: DOAJ

【 摘 要 】

BackgroundThe effect of gene polymorphisms and promoter methylation, associated with maladaptive developmental outcomes, vary depending on environmental factors (e.g., parental psychopathology). Most studies have focused on 0- to 5-year-old children, adolescents, or adults, whereas there is dearth of research on school-age youths and pre-adolescents.MethodsIn a sample of 21 families recruited at schools, we addressed parents’ psychopathological symptoms (through SCL-90-R); offspring emotional–behavioral functioning (through CBCL-6–18); dopamine transporter gene (DAT1) for epigenetic status of the 5′-untranslated region (UTR) and for genotype, i.e., variable number of tandem repeats polymorphism at the 3′-UTR. Possible associations were explored between bio-genetic and psychological characteristics within the same individual and between triplets of children, mothers, and fathers.ResultsDAT methylation of CpG at positions M1, M6, and M7 in mothers was correlated with maternal (phobic) anxiety, whereas in fathers’ position M6 was related to paternal depression, anxiety, hostility, psychoticism, and higher Global Severity Index (GSI). No significant correlations were found between maternal and offspring DAT methylation. Significant correlations were found between fathers’ methylation at CpG M1 and children’s methylation at CpG M6. Linear regressions showed that mothers and fathers’ GSI predicted children’s methylation at CpG sites M2, M3, and M6, whereas fathers’ GSI predicted children’s methylation at CpG sites, particularly M1, M2, and M6. Moreover, offspring methylation of DAT at CpG M2 predicted somatic complaint, internalizing and attention problems; methylation of DAT at CpG M6 predicted withdraw.ConclusionThis study may have important clinical implication for the prevention and treatment of emotional–behavioral difficulties in children, as it adds to previous knowledge about the role of genetic and environmental factors in predicting psychopathological symptoms within non-clinical populations.

【 授权许可】

Unknown