Abstract
Congenital absence of monoamine oxidase A (MAO-A) activity predisposes to antisocial impulsive behaviour, and the MAOA uVNTR low-expressing genotype (MAOA-L) together with childhood maltreatment is associated with similar phenotypes in males. A possible explanation of how family environment may lead to such behaviour involves DNA methylation. We have assessed MAOA methylation and impulsive/antisocial behaviour in 121 males from the Estonian Children Personality Behaviour and Health Study. Of the 12 CpG sites measured, methylation levels at the locus designated CpG3 were significantly lower in subjects with antisocial behaviour involving police contact. CpG3 methylation was lower in subjects with alcohol use disorder by age 25, but only in MAOA-H genotype. No correlation between MAOA CpG3 methylation levels and adaptive impulsivity was found at age 15, but in MAOA-L genotype a positive correlation appeared by age 18. By age 25, this positive correlation was no longer observed in subjects with better family relationships but had increased further with experience of adversity within the family. MAOA CpG3 methylation had different developmental dynamics in relation to maladaptive impulsivity. At age 18, a positive correlation was observed in MAOA-L genotype with inferior family relationships and a negative correlation was found in MAOA-H with superior home environment; both of these associations had disappeared by age 25. CpG3 methylation was associated with dietary intake of several micronutrients, most notable was a negative correlation with the intake of zinc, but also with calcium, potassium and vitamin E; a positive correlation was found with intake of phosphorus. In conclusion, MAOA CpG3 methylation is related to both maladaptive and adaptive impulsivity in adolescence in MAOA-L males from adverse home environment. By young adulthood, this relationship with maladaptive impulsivity had disappeared but with adaptive impulsivity strengthened. Thus, MAOA CpG3 methylation may serve as a marker for adaptive developmental neuroplasticity in MAOA-L genotype. The mechanisms involved may include dietary factors.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors are grateful to the ECPBHS participants and the whole ECPBHS Team. This work was supported by the Estonian Research Council (PRG1213), the European Commission Horizon 2020 Program Project Eat2beNICE (no. 728018), Serotonin and Beyond (no. 953327) and the Horizon Europe Research and Innovation Program Project Aqua-Synapse (no. EU 101086453). Arunima Roy was supported by the Alexander von Humboldt Stiftung to participate in this study. The funding agencies had no role in the design of the study; data collection, analysis, and the interpretation of the results provided in the manuscript. This article was prepared while Denis Matrov was employed at the University of Tartu. The opinions expressed in this article are the author’s own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. We thank Gabriele Ortega for excellent technical assistance.
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Conceptualisation: MK, KS, KPL, TV, JH; methodology: MK, KS, DM, AR, GCZ, KPL, JH; formal analysis and investigation: MK, KS, DM, TK, JH; writing: original draft preparation: MK, KS, JH; review and editing: MK, KS, DM, TK, AR, GCZ, TV, KPL, JH; funding acquisition: TV, KPL, JH; resources: TV, KPL, JH; supervision: TV, KPL, JH.
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Kanarik, M., Sakala, K., Matrov, D. et al. MAOA methylation is associated with impulsive and antisocial behaviour: dependence on allelic variation, family environment and diet. J Neural Transm 131, 59–71 (2024). https://doi.org/10.1007/s00702-023-02675-w
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DOI: https://doi.org/10.1007/s00702-023-02675-w