No association between peripheral serotonin-gene-related DNA methylation and brain serotonin neurotransmission in the healthy and depressed state.
Humans
DNA Methylation
/ genetics
Serotonin Plasma Membrane Transport Proteins
/ genetics
Male
Female
Adult
Tryptophan Hydroxylase
/ genetics
Serotonin
/ metabolism
Brain
/ metabolism
Depression
/ genetics
Epigenesis, Genetic
/ genetics
Synaptic Transmission
/ genetics
CpG Islands
/ genetics
Middle Aged
Young Adult
Receptors, Serotonin, 5-HT4
/ genetics
Positron-Emission Tomography
Cohort Studies
5-HT
Depression
Early life stress
Epigenetics
Human brain imaging
Mood disorders
PET
Serotonin 4 receptor
Serotonin transporter
TPH2
Tryptophan hydroxylase 2
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
27 May 2024
27 May 2024
Historique:
received:
19
01
2024
accepted:
06
05
2024
medline:
28
5
2024
pubmed:
28
5
2024
entrez:
27
5
2024
Statut:
epublish
Résumé
Methylation of serotonin-related genes has been proposed as a plausible gene-by-environment link which may mediate environmental stress, depressive and anxiety symptoms. DNA methylation is often measured in blood cells, but little is known about the association between this peripheral epigenetic modification and brain serotonergic architecture. Here, we evaluated the association between whole-blood-derived methylation of four CpG sites in the serotonin transporter (SLC6A4) and six CpG sites of the tryptophan hydroxylase 2 (TPH2) gene and in-vivo brain levels of serotonin transporter (5-HTT) and serotonin 4 receptor (5-HT We found no statistically significant association between peripheral DNA methylation and brain markers of serotonergic neurotransmission in patients with depression or in healthy individuals. In addition, although SLC6A4 CpG2 (chr17:30,236,083) methylation was marginally associated with the parental bonding inventory overprotection score in the healthy cohort, statistical significance did not remain after accounting for blood cell heterogeneity. We suggest that findings on peripheral DNA methylation in the context of brain serotonin-related features should be interpreted with caution. More studies are needed to rule out a role of SLC6A4 and TPH2 methylation as biomarkers for environmental stress, depressive or anxiety symptoms.
Sections du résumé
BACKGROUND
BACKGROUND
Methylation of serotonin-related genes has been proposed as a plausible gene-by-environment link which may mediate environmental stress, depressive and anxiety symptoms. DNA methylation is often measured in blood cells, but little is known about the association between this peripheral epigenetic modification and brain serotonergic architecture. Here, we evaluated the association between whole-blood-derived methylation of four CpG sites in the serotonin transporter (SLC6A4) and six CpG sites of the tryptophan hydroxylase 2 (TPH2) gene and in-vivo brain levels of serotonin transporter (5-HTT) and serotonin 4 receptor (5-HT
RESULTS
RESULTS
We found no statistically significant association between peripheral DNA methylation and brain markers of serotonergic neurotransmission in patients with depression or in healthy individuals. In addition, although SLC6A4 CpG2 (chr17:30,236,083) methylation was marginally associated with the parental bonding inventory overprotection score in the healthy cohort, statistical significance did not remain after accounting for blood cell heterogeneity.
CONCLUSIONS
CONCLUSIONS
We suggest that findings on peripheral DNA methylation in the context of brain serotonin-related features should be interpreted with caution. More studies are needed to rule out a role of SLC6A4 and TPH2 methylation as biomarkers for environmental stress, depressive or anxiety symptoms.
Identifiants
pubmed: 38802956
doi: 10.1186/s13148-024-01678-y
pii: 10.1186/s13148-024-01678-y
doi:
Substances chimiques
Serotonin Plasma Membrane Transport Proteins
0
Tryptophan Hydroxylase
EC 1.14.16.4
SLC6A4 protein, human
0
Serotonin
333DO1RDJY
TPH2 protein, human
EC 1.14.16.4
Receptors, Serotonin, 5-HT4
158165-40-3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
71Subventions
Organisme : Horizon 2020
ID : 953327
Organisme : Horizon 2020
ID : 953327
Organisme : Horizon 2020
ID : 953327
Organisme : Horizon 2020
ID : 953327
Organisme : Innovationsfonden
ID : 5189-00087A
Organisme : Innovationsfonden
ID : 5189-00087A
Organisme : Innovationsfonden
ID : 5189-00087A
Organisme : Innovationsfonden
ID : 5189-00087A
Organisme : Innovationsfonden
ID : 5189-00087A
Organisme : Lundbeck Foundation
ID : R279-2018-1145
Organisme : Lundbeck Foundation
ID : R279-2018-1145
Organisme : Lundbeck Foundation
ID : R279-2018-1145
Organisme : Lundbeck Foundation
ID : R279-2018-1145
Organisme : Research Council of Rigshospitalet
ID : A6594
Informations de copyright
© 2024. The Author(s).
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