Brain serotonin 1A receptor binding: relationship to peripheral blood DNA methylation, recent life stress and childhood adversity in unmedicated major depression.
Br J Psychiatry
; 223(3): 415-421, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37395098
ABSTRACT
BACKGROUND:
Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.AIMS:
We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls).METHOD:
Medication-free participants with MDD (n = 192 110 female, 81 male, 1 other) and controls (n = 88 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (-1019, -1007, -681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF.RESULTS:
Recent stress correlated positively with blood monocyte methylation at the -681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the -1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD.CONCLUSIONS:
These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transtorno Depressivo Maior
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Br J Psychiatry
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos