Dataset Information

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

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-HT_1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT_1A receptor binding potential (BP_F) 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-HT_1A receptor gene. A subgroup (n = 119) had regional brain 5-HT_1A receptor BP_F quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BP_F.

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-HT_1A BP_F 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_F in participants with MDD.

Conclusions

These findings support a model in which recent stress increases 5-HT_1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

SUBMITTER: Galfalvy H

PROVIDER: S-EPMC10514224 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Galfalvy Hanga H Shea Eileen E de Vegvar Jacqueline J Pantazatos Spiro S Huang Yung-Yu YY Burke Ainsley K AK Sublette M Elizabeth ME Oquendo Maria A MA Zanderigo Francesca F Miller Jeffrey M JM Mann J John JJ

The British journal of psychiatry : the journal of mental science 20230901 3

<h4>Background</h4>Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.<h4>Aims</h4>We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT<sub>1A</sub>) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and <i>in vivo</i> 5-HT<sub>1A</sub> receptor binding potential (BP<sub>F</sub>) determined by positron emission tomography (PET) in 13 <i>a priori</i> brain regions, in pa ...[more]

PMID: 37395098

Similar Datasets

Project description:BACKGROUND:College students are at risk of depression. This risk may be increased by the experience of childhood adversity and/or recent stressors. This study examined the association between reported experiences of childhood adversity, recent stressors and depression during the last 12 months in a cohort of South African university students. METHODS:Six hundred and eighty-six first year students at Stellenbosch University in South Africa completed a health-focused e-survey that included items on childhood adversity, recent stressors and mood. Individual and population attributable risk proportions (PARP) between experiences of childhood adversity and 12-month stressful experiences and 12-month depression were estimated using multivariate binomial logistic regression analysis. RESULTS:About one in six students reported depression during the last 12 months. Being a victim of bullying and emotional abuse or emotional neglect during childhood were the strongest predictors of depression in the past year at both individual and population level. With regard to recent stressors, a romantic partner being unfaithful, serious ongoing arguments or break-ups with some other close friend or family member and a sexual or gender identity crisis were the strongest predictors of depression. The predictor effect of recent stressors was significantly reduced in the final model that adjusted for the type and number of childhood traumatic experiences. At a population level, academic stress, serious ongoing arguments or break-ups with a close friend or family member, and serious betrayal by someone close were the variables that yielded the highest PARP. CONCLUSIONS:Our findings suggest a significant relationship between early adversity, recent stressors, and depression here and throughout, consistent with the broader literature on predictors of depression. This study contributes to the limited data on college students' mental health in low and middle income countries including on the African continent. The findings provide information on the population level effect sizes of trauma as a risk factor for depression, as well as on the relationship between specific recent stressors and depression in college students.

Dataset Information

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

Background

Aims

Method

Results

Conclusions

Publications

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

Similar Datasets

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