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Methylation of NR3C1 and SLC6A4 and internalizing problems. The TRAILS study.

Abstract：

BACKGROUND:The relationship between early adverse life events and later internalizing problems could be mediated by DNA methylation. Adversity has been associated with higher methylation levels in the glucocorticoid receptor gene (NR3C1) and the serotonin transporter gene (SLC6A4) in adolescents. We investigated cross-sectional and prospective associations of NR3C1 and SLC6A4 methylation with adolescents׳ clinical diagnoses of internalizing disorders and internalizing symptom scores. METHODS:In a population sample (mean age=16.2) we measured DNA methylation in three regions of NR3C1 (NR3C1_1, N=454; NR3C1_2, N=904; NR3C1_3, N=412) and one region of SLC6A4 (N=939) at baseline. Internalizing problems were operationalized as clinical DSM-IV diagnoses, assessed at 3 year follow-up with a diagnostic interview, and internalizing symptom scores, assessed with Self-Report questionnaires at baseline and follow-up. RESULTS:Only NR3C1_1 methylation was positively associated with risk of lifetime internalizing disorders, and with symptom scores at follow-up. However, after accounting for baseline symptom scores there was only a tendency for association with internalizing symptom scores at follow-up. There was no association between SLC6A4 methylation and risk of lifetime internalizing disorders. SLC6A4 methylation and internalizing symptom scores showed a tendency for association, also after accounting for baseline symptom scores. LIMITATIONS:There was no repeated measure of DNA methylation to study causality between methylation and internalizing problems. Gene expression data were not available. CONCLUSIONS:Although the role of gene methylation in the development of internalizing problems remains unclear, our findings suggest that gene methylation, particularly of NR3C1, may be involved in the development of internalizing problems in adolescence.

journal_name

J Affect Disord

journal_title

Journal of affective disorders

authors

van der Knaap LJ,van Oort FV,Verhulst FC,Oldehinkel AJ,Riese H

doi

10.1016/j.jad.2015.03.056

subject

Has Abstract

pub_date

2015-07-15 00:00:00

pages

97-103

eissn

0165-0327

issn

1573-2517

pii

S0165-0327(15)00195-0

journal_volume

180

pub_type

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Methylation of NR3C1 and SLC6A4 and internalizing problems. The TRAILS study.