Serotonin transporter gene promoter methylation in peripheral cells in healthy adults: Neural correlates and tissue specificity

Autor: Gustavo Turecki, Gabriella Gobbi, Richard E. Tremblay, Moshe Szyf, Elmira Ismaylova, Frank Vitaro, Zsofia Nemoda, Jessica Di Sante, Wei-Jo Yu, Florence B. Pomares, Linda Booij
Rok vydání: 2017
Předmět:
0301 basic medicine
Adult
Male
Pathology
medicine.medical_specialty
Rest
Buccal swab
03 medical and health sciences
0302 clinical medicine
Parietal Lobe
medicine
Limbic System
Humans
Pharmacology (medical)
Epigenetics
Longitudinal Studies
Prospective Studies
Gray Matter
Promoter Regions
Genetic
Saliva
Biological Psychiatry
Serotonin transporter
Pharmacology
Serotonin Plasma Membrane Transport Proteins
Brain Mapping
medicine.diagnostic_test
biology
Promoter
Epithelial Cells
Human brain
Methylation
DNA Methylation
Magnetic Resonance Imaging
Frontal Lobe
Psychiatry and Mental health
030104 developmental biology
medicine.anatomical_structure
Cheek
Neurology
DNA methylation
biology.protein
Female
Neurology (clinical)
Functional magnetic resonance imaging
030217 neurology & neurosurgery
Follow-Up Studies
Zdroj: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 27(10)
ISSN: 1873-7862
Popis: Early adversity can influence gene expression via epigenetic mechanisms, including DNA methylation. Peripheral tissues are essential in psychiatric epigenetics, as methylation generally cannot be assessed in the living human brain. Several magnetic resonance imaging (MRI) studies show associations of peripheral serotonin transporter gene (SLC6A4) methylation with function and/or structure of frontal-limbic circuits and brain's resting-state. Commonly used samples are derived from blood, saliva or buccal cells. However, little is known regarding which peripheral tissue is most strongly associated with human brain processes. The aim of the current study was to compare the extent of the association between peripheral SLC6A4 promoter methylation and frontal-limbic function, structure and resting-state in healthy individuals across peripheral tissues. Forty healthy prospectively-followed adults underwent anatomical, resting-state and functional MRI. Saliva-, blood- and buccal-derived DNA methylation was assessed by pyrosequencing. Blood-derived SLC6A4 methylation was positively associated with superior frontal gray matter (GM) volume and with right lateral parietal area (RLP)-frontal pole regional resting-state functional connectivity (rsFC). Saliva-derived SLC6A4 methylation was positively associated with superior frontal GM volume. Buccal-derived SLC6A4 methylation was positively associated with superior and inferior frontal and anterior cingulate cortical (ACC) GM volumes, and with RLP-ACC, frontal pole and medial prefrontal regional rsFC. Current results confirmed the relevance of peripheral methylation for frontal-limbic processes in humans. Buccal cells may be the most sensitive cell type when studying SLC6A4 promoter methylation and its associated risk for neural vulnerability and resilience for psychopathologies in which serotonin is implicated. These data should be further validated in clinical populations.
Databáze: OpenAIRE
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