DNA methylation at the DAT promoter and risk for psychopathology: Intergenerational transmission between school-age youths and their parents in a community sample

Silvia Cimino, Luca Cerniglia, Giulia Ballarotto, Eleonora Marzilli, Esterina Pascale, Claudio D'Addario, Walter Adriani, Renata Tambelli

Research output: Contribution to journalArticle

Abstract

Background: The 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. Methods: In 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. Results: DAT 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. Conclusion: This 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.

Original languageEnglish
Article number303
JournalFrontiers in Psychiatry
Volume8
Issue numberJAN
DOIs
Publication statusPublished - Jan 10 2018

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DNA Methylation
Psychopathology
Methylation
Parents
Fathers
Mothers
Anxiety
Minisatellite Repeats
Dopamine Plasma Membrane Transport Proteins
Hostility
5' Untranslated Regions
3' Untranslated Regions
Epigenomics
Genes
Linear Models
Genotype
Depression
Psychology
Research

Keywords

  • 5'-untranslated region
  • DAT
  • Epigenetics
  • Genotype
  • Intergenerational transmission
  • Methylation
  • Psychopathological symptoms
  • Variable number of tandem repeats polymorphism

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

DNA methylation at the DAT promoter and risk for psychopathology : Intergenerational transmission between school-age youths and their parents in a community sample. / Cimino, Silvia; Cerniglia, Luca; Ballarotto, Giulia; Marzilli, Eleonora; Pascale, Esterina; D'Addario, Claudio; Adriani, Walter; Tambelli, Renata.

In: Frontiers in Psychiatry, Vol. 8, No. JAN, 303, 10.01.2018.

Research output: Contribution to journalArticle

Cimino, Silvia ; Cerniglia, Luca ; Ballarotto, Giulia ; Marzilli, Eleonora ; Pascale, Esterina ; D'Addario, Claudio ; Adriani, Walter ; Tambelli, Renata. / DNA methylation at the DAT promoter and risk for psychopathology : Intergenerational transmission between school-age youths and their parents in a community sample. In: Frontiers in Psychiatry. 2018 ; Vol. 8, No. JAN.
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T1 - DNA methylation at the DAT promoter and risk for psychopathology

T2 - Intergenerational transmission between school-age youths and their parents in a community sample

AU - Cimino, Silvia

AU - Cerniglia, Luca

AU - Ballarotto, Giulia

AU - Marzilli, Eleonora

AU - Pascale, Esterina

AU - D'Addario, Claudio

AU - Adriani, Walter

AU - Tambelli, Renata

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N2 - Background: The 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. Methods: In 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. Results: DAT 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. Conclusion: This 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.

AB - Background: The 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. Methods: In 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. Results: DAT 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. Conclusion: This 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.

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