DNA methylation differences in stress-related genes, functional connectivity and gray matter volume in depressed and healthy adolescents.
Adolescent depression
Brain structure
DNA methylation
Epigenetics
Functional connectivity
Journal
Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073
Informations de publication
Date de publication:
15 06 2020
15 06 2020
Historique:
received:
04
10
2019
revised:
09
01
2020
accepted:
22
03
2020
entrez:
2
6
2020
pubmed:
2
6
2020
medline:
16
2
2021
Statut:
ppublish
Résumé
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. 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. 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. Effects of medication use or genotype cannot be ruled out. Further, the relatively small sample size and predominately female sample may limit generalizability. 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.
Sections du résumé
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.
Identifiants
pubmed: 32479312
pii: S0165-0327(19)32701-6
doi: 10.1016/j.jad.2020.03.062
pii:
doi:
Substances chimiques
SLC6A4 protein, human
0
Serotonin Plasma Membrane Transport Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
160-168Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All authors declare that they have no conflict of interest.