Abstract

Epigenetic mechanisms, in particular DNA methylation, have been implicated in the etiopathogenesis of psychopathologies in adulthood. The significance of this mechanism in child psychopathologies, however, is much less recognized. Here, we examined whether global DNA methylation alteration was associated with the presence of disruptive mood dysregulation disorder (DMDD) in children. Moreover, in light of the relevance of the interplay between children and parents for the onset and maintaining of psychopathology during development, we measured the association between psychological symptoms, attachment styles, and global DNA methylation levels in healthy and DMDD mother-child dyads (mothers: N = 126, age = 38.3 ± 2.5 years; children: N = 150, age = 8.2 ± 0.9 years, gender ratio [f/m] = 72/78). We did not observe any significant differences in global DNA methylation levels in DMDD children when compared with healthy peers, and children's symptoms did not correlate with variations in this parameter. The mothers showed different levels of psychological symptomatology. Notably, mothers with high psychological symptomatology showed the lowest levels of global DNA methylation. Maternal global DNA methylation levels were associated with maternal hostility, interpersonal sensitivity, psychoticism, and general severity index. Moreover, we found an effect of maternal mental health on the severity of children's symptoms, independently from both maternal and child DNA methylation levels. Despite here DNA methylation does not appear to be involved in the maternal inheritance of vulnerability to depression, this biological link could still arise in later stages of the child's development.

Highlights

  • Bio-psycho-social approaches that highlight the interplay of the child, parent, family, and other environmental factors are commonly used to depict the complexity of psychopathology during child development [1, 2]

  • In light of recent evidence consistently describing an alteration of DNA methylation in mood disorders in adulthood [18], here we hypothesize that children with a diagnosis of disruptive mood dysregulation disorder (DMDD) experience decreased global DNA methylation levels and such changes are negatively associated with psychological symptoms and attachment style

  • In light of the evidence that global DNA methylation in the blood differs between clinical syndromes and that it mediates the effects of primary affective relationships on the child development [33], we evaluated if this parameter was differentially modulated in distinct samples of children characterized by different diagnosis and attachment style

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Summary

INTRODUCTION

Bio-psycho-social approaches that highlight the interplay of the child, parent, family, and other environmental factors are commonly used to depict the complexity of psychopathology during child development [1, 2]. In light of recent evidence consistently describing an alteration of DNA methylation in mood disorders in adulthood [18], here we hypothesize that children with a diagnosis of DMDD experience decreased global DNA methylation levels and such changes are negatively associated with psychological symptoms and attachment style. Parents’ experiences may transfer epigenetic marks that impact offspring development alone and in interaction with offspring exposure to perinatal and childhood stress [11, 21] Based on these premises we hypothesize that the effect of maternal mental health on child’s symptoms may be mediated by maternal and/or childhood DNA methylation. We measured this parameter in healthy and clinical (DMDD) mother-child dyads and examined its association with maternal and child psychological symptoms and attachment style

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Procedure for Biological Sampling
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