SLC25A24 gene methylation and gray matter volume in females with and without conduct disorder: an exploratory epigenetic neuroimaging study

Elizabeth Farrow, Andreas G. Chiocchetti, Jack Rogers, Ruth Pauli, Nora Maria Raschle, Karen Gonzalez-Madruga, Areti Smaragdi, Anne Martinelli, Gregor Kohls, Christina Stadler, Kerstin Konrad, Graeme Fairchild, Christine M. Freitag, Magda Chechlacz, Stephane De Brito

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Abstract

Conduct disorder (CD), a psychiatric disorder characterized by a repetitive pattern of antisocial behaviors, results from a complex interplay between genetic and environmental factors. The clinical presentation of CD varies both according to the individual’s sex and level of callous-unemotional (CU) traits, but it remains unclear how genetic and environmental factors interact at the molecular level to produce these differences. Emerging evidence in males implicates methylation of genes associated with socio-affective processes. Here, we combined an epigenome-wide association study with structural neuroimaging in 51 females with CD and 59 typically developing (TD) females to examine DNA methylation in relation to CD, CU traits, and gray matter volume (GMV). We demonstrate an inverse pattern of correlation between CU traits and methylation of a chromosome 1 region in CD females (positive) as compared to TD females (negative). The identified region spans exon 1 of the SLC25A24 gene, central to energy metabolism due to its role in mitochondrial function. Increased SLC25A24 methylation was also related to lower GMV in multiple brain regions in the overall cohort. These included the superior frontal gyrus, prefrontal cortex, and supramarginal gyrus, secondary visual cortex and ventral posterior cingulate cortex, which are regions that have previously been implicated in CD and CU traits. While our findings are preliminary and need to be replicated in larger samples, they provide novel evidence that CU traits in females are associated with methylation levels in a fundamentally different way in CD and TD, which in turn may relate to observable variations in GMV across the brain.
Original languageEnglish
Article number492
Number of pages9
JournalTranslational Psychiatry
Volume11
Issue number1
Early online date24 Sep 2021
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
This study was conducted as part of the FemNAT-CD consortium (Neurobiology and treatment of adolescent female conduct disorder: The Central Role of Emotion Processing, coordinator Christine M. Freitag). This collaborative project is funded by the European Commission under the 7th Framework Health Program with Grant Agreement no. 602407. We would like to thank all members of the FemNAT-CD consortium for their contributions to the project. We would also like to thank our participants, their families, and the numerous teachers, clinicians, social workers, foster carers and other professionals who gave their time generously to assist with recruitment and participate in the study.

Funding Information:
As stated above, all the authors of this paper were involved in the FemNAT-CD project, which was funded by the European Commission under the 7th Framework Health Program with Grant Agreement no. 602407. Elizabeth Farrow is a Ph.D. student funded by the Biotechnology and Biological Sciences Research Council (BBSRC)’s Midlands Integrative Biosciences Training Partnership (MIBTP). Professor Christine Freitag receives royalties for books on ASD, ADHD, and MDD from the following German publishes Beltz, Hogrefe, Kohlhammer, Springer, Reinhardt. During the writing of this manuscript Stephane A. De Brito was supported by a short-term Invitational Fellowship from the Japanese Society for the Promotion of Science (JSPS-S19103) and an International Academic Fellowship from the Leverhulme Trust (IAF-2019-032). To the authors’ knowledge, there are no other biomedical financial interests or potential competing interests.

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • Antiporters/genetics
  • Calcium-Binding Proteins/genetics
  • Conduct Disorder/diagnostic imaging
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Gray Matter/diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mitochondrial Proteins/genetics
  • Neuroimaging

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Cellular and Molecular Neuroscience

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