Peripheral serotonin transporter DNA methylation is linked to increased salience network connectivity in females with anorexia nervosa

Research output: Contribution to journalResearch articleContributedpeer-review


Background: Epigenetic variation in the serotonin transporter gene (SLC6A4) has been shown to modulate the functioning of brain circuitry associated with the salience network and may heighten the risk for mental illness. This study is, to our knowledge, the first to test this epigenome–brain–behaviour pathway in patients with anorexia nervosa.

Methods: We obtained resting-state functional connectivity (rsFC) data and blood samples from 55 acutely underweight female patients with anorexia nervosa and 55 age-matched female healthy controls. We decomposed imaging data using independent component analysis. We used bisulfite pyrosequencing to analyze blood DNA methylation within the promoter region of SLC6A4. We then explored salience network rsFC patterns in the group × methylation interaction.

Results: We identified a positive relationship between SLC6A4 methylation levels and rsFC between the dorsolateral prefrontal cortex and the salience network in patients with anorexia nervosa compared to healthy controls. Increased rsFC in the salience network mediated the link between SLC6A4 methylation and eating disorder symptoms in patients with anorexia nervosa. We confirmed findings of rsFC alterations for CpG-specific methylation at a locus with evidence of methylation correspondence between brain and blood tissue.

Limitations: This study was cross-sectional in nature, the sample size was modest for the method and methylation levels were measured peripherally, so findings cannot be fully generalized to brain tissue.

Conclusion: This study sheds light on the neurobiological process of how epigenetic variation in the SLC6A4 gene may relate to rsFC in the salience network that is linked to psychopathology in anorexia nervosa.


Original languageEnglish
Pages (from-to)206-213
Number of pages8
JournalJournal of psychiatry & neuroscience: JPN
Issue number3
Early online date5 Dec 2019
Publication statusPublished - 1 May 2020

External IDs

Scopus 85083975625
PubMed 31823595
PubMedCentral PMC7828979
ORCID /0000-0002-2864-5578/work/142233460
ORCID /0000-0003-2132-4445/work/142236330


Sustainable Development Goals


  • Adolescent, Adult, Anorexia Nervosa/diagnostic imaging, Brain/diagnostic imaging, Case-Control Studies, Child, DNA Methylation/genetics, Female, Functional Neuroimaging, Humans, Magnetic Resonance Imaging, Neural Pathways/diagnostic imaging, Serotonin Plasma Membrane Transport Proteins/genetics, Young Adult