Brain serotonin 1A receptor binding: relationship to peripheral blood DNA methylation, recent life stress and childhood adversity in unmedicated major depression

Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms. We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT ) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and 5-HT recept...

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Bibliographic Details
Published in:British journal of psychiatry 2023-09, Vol.223 (3), p.415-421
Main Authors: Galfalvy, Hanga, Shea, Eileen, de Vegvar, Jacqueline, Pantazatos, Spiro, Huang, Yung-yu, Burke, Ainsley K., Sublette, M. Elizabeth, Oquendo, Maria A., Zanderigo, Francesca, Miller, Jeffrey M., Mann, J. John
Format: Article
Language:English
Subjects:
Adverse childhood experiences
Adversity
Blood
Brain
Brain - pathology
Brain serotonin
Childhood
Children
CpG islands
Deoxyribonucleic acid
Depression
Depressive Disorder, Major - diagnostic imaging
Depressive Disorder, Major - drug therapy
Depressive Disorder, Major - genetics
Depressive personality disorders
Diagnosis
DNA
DNA Methylation
Drugs
Epigenetics
Female
Gender
General Adult
Genotype & phenotype
Genotypes
Humans
Life stress
Magnetic resonance imaging
Male
Medical diagnosis
Mental depression
Monocytes
Neurotransmission
Peripheral blood
Plasma
Positron emission tomography
Positron-Emission Tomography - methods
Psychiatry
Psychopathology
Psychotropic drugs
Receptor, Serotonin, 5-HT1A - genetics
Receptor, Serotonin, 5-HT1A - metabolism
Receptor, Serotonin, 5-HT1A - therapeutic use
Serotonin - metabolism
Serotonin - therapeutic use
Serotonin receptors
Serotonin S1 receptors
Statistical analysis
Stress
Stress, Psychological - genetics
Suicidal behavior
Tomography
Volunteers
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Summary:Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms. We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT ) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and 5-HT receptor binding potential (BP ) determined by positron emission tomography (PET) in 13 brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls). Medication-free participants with MDD ( = 192: 110 female, 81 male, 1 other) and controls ( = 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-HT receptor gene. A subgroup ( = 119) had regional brain 5-HT receptor BP quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BP . 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-HT BP 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 BP in participants with MDD. These findings support a model in which recent stress increases 5-HT receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.
ISSN:0007-1250
1472-1465
DOI:10.1192/bjp.2023.13