Childhood emotional neglect and oxytocin receptor variants: Association with limbic brain volumes

Abstract

Objectives: Childhood emotional neglect (EN) is a predictor for the development of affective disorders. Oxytocin (OXT) may mediate the interplay between EN and changes in stress biological systems, brain development, and mental health outcomes. We investigated, in a cross-sectional study, the associations between EN, (epi)genetic variation in the OXT receptor (OXTR) gene, and amygdalar and hippocampal volumes, two brain regions implicated in emotional processing.

Methods: We recruited 63 Caucasian South African adults (35 women) with and without social anxiety disorder. Childhood EN was assessed using the Childhood Trauma Questionnaire. rs53576 and rs2254298 genotypes, as well as methylation status, was determined using DNA purified from whole blood. Bilateral amygdalar and hippocampal volumes were determined by structural magnetic resonance imaging. The relationships between these variables were investigated using linear regression.

Results: The interaction of the rs2254298 A risk allele and EN was nominally associated with reduced left hippocampal volume. The rs2254298 A risk allele was independently associated with reduced bilateral amygdalar volumes. We found no association between EN, OXTR methylation and amygdalar or hippocampal volumes. The rs53576 GG risk genotype was, however, associated with decreased OXTR methylation.

Conclusions: The rs2254298 A allele may increase susceptibility to the structural brain effects of EN.

Keywords:

• Childhood trauma
• DNA methylation
• emotional neglect
• neuroimaging
• oxytocin receptor

Acknowledgements

None.

Disclosure statement

The authors report no conflicts of interest.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work is based upon research supported by the South African Research Chair in PTSD from the Department of Science and Technology and the National Research Foundation (SMJH, JSW, AG, FA, DR, SS) as well as a South African Medical Research Council “SHARED ROOTS” Flagship Project, grant MRC-RFA-IFSP-01-2013/SHARED ROOTS (SMJH, SS). This work was further supported by the German Medical Research Foundation (DFG), SFB-TRR-58, projects C02 and Z02 (to KD), and the German Ministry of Research and Education (BMBF, 01EE1402F, PROTECT-AD, P5 to KD). We gratefully acknowledge the skilful technical assistance by Carola Gagel. This work supported by Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft.