1 Department of Psychology, Concordia University, Montreal, Canada; CHU Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Canada; Department of Psychology, Queen's University, Kingston, Canada.
2 Department of Psychology, Queen's University, Kingston, Canada.
3 Department of Psychology, Concordia University, Montreal, Canada.
4 Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany.
5 Department of Psychiatry, Trinity College School of Medicine and Trinity College Institute of Neuroscience, Dublin, Ireland.
6 Department of Psychology, Concordia University, Montreal, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada; Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
7 Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
8 Department of Psychiatry, Division of Child Psychiatry, Hotel Dieu Hospital, Queen's University, Kingston, Canada.
9 Department of Psychology, Concordia University, Montreal, Canada; CHU Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Canada; Department of Psychology, Queen's University, Kingston, Canada. Electronic address: linda.booij@concordia.ca.

DNA methylation differences in stress-related genes, functional connectivity and gray matter volume in depressed and healthy adolescents.

J Affect Disord. 2020 Jun 15;271:160-168

Authors: Chiarella J, Schumann L, Pomares FB, Frodl T, Tozzi L, Nemoda Z, Yu P, Szyf M, Khalid-Khan S, Booij L

Abstract

BACKGROUND: Studies in adult depressed patients have indicated that altered DNA methylation patterns at genes related to serotonin and HPA axis functioning (e.g., SLC6A4, FKBP5) are associated with changes in frontolimbic functional connectivity and structure. Here, we examined whether these associations can be generalized to adolescents.

METHODS: 25 adolescents with depression (Mean age = 15.72 ± 0.94 SD; 20 girls) and 20 healthy controls (Mean age = 16.05 ± 1.5 SD; 16 girls) underwent a functional and structural magnetic resonance imaging protocol, which included a resting-state assessment and measures of brain morphometry. DNA was obtained from saliva. Levels of SLC6A4 and FKBP5 methylation were determined using pyrosequencing.

RESULTS: SLC6A4 methylation was linked to amygdala-frontal operculum resting-state functional connectivity (rs-FC), regardless of diagnosis, and was differentially associated with inferior orbitofrontal gyrus (IFOG) gray matter (GM) volume in adolescents with depression and controls. Replicating and extending previous findings in adults, FKBP5 methylation was associated with IFOG GM volume in depressed and healthy adolescents, as well as orbitofrontal cortex (OFC)-rostral prefrontal cortex (RPFC) connectivity in healthy adolescents only.

LIMITATIONS: Effects of medication use or genotype cannot be ruled out. Further, the relatively small sample size and predominately female sample may limit generalizability.

CONCLUSIONS: These findings suggest that previously observed associations between SLC6A4 and FKBP5 methylation and frontolimbic processes in adult depressed patients can be in part generalized to adolescent patients. Further, findings suggest that measuring peripheral methylation at these genes deserves further attention as potential markers of typical and atypical development.

PMID: 32479312 [PubMed - as supplied by publisher]