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Child MTHFR C677T genotype and HPA stress regulation at 6 years of age
Author(s) -
Hookenson Kaia Vivian,
Weinberg Joanne,
Brain Ursula,
Devlin Angela M,
Oberlander Tim F
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.936.14
Subject(s) - evening , methylenetetrahydrofolate reductase , offspring , morning , endocrinology , medicine , depression (economics) , mood , cortisol awakening response , genotype , mood disorders , hypothalamic–pituitary–adrenal axis , psychology , pregnancy , physiology , hydrocortisone , hormone , psychiatry , biology , genetics , gene , anxiety , physics , macroeconomics , astronomy , economics
Major depression is often characterized by elevated daily cortisol concentrations reflecting altered hypothalamic pituitary adrenal (HPA) regulation. A dysregulated maternal HPA axis may exert early programming effects on fetal HPA activity. The methylenetetrahydrofolate reductase ( MTHFR ) gene, an enzyme required for folate metabolism, has a variant (C677T) associated with depression. It remains unknown whether the C677T variant moderates the effect of antenatal maternal depression in shaping HPA function during early childhood. To study if an association between antenatal maternal mood and offspring HPA regulation may be moderated by C677T genotype, salivary cortisol concentrations were obtained from children (n=59) over four days [early morning awakening (mean 7:42 ± 0.91 h), 15 min later (8:02 ± .96 h), and evening (18:40 ± 2.35 h)]. Using a linear regression model, prenatal SRI antidepressant exposure, and maternal mood (Hamilton Depression Rating Scale) at 33 weeks and 6 years, did not predict cortisol concentrations. However, children with 677TT genotype (n=9) had higher evening cortisol concentrations (β=−0.384, P=0.004), and a smaller change from early morning to evening (β=0.292, P=0.037), compared to children with 677CC and CT. These data suggest that children with a MTHFR 677TT genotype have both elevated and altered diurnal cortisol patterns, possibly indicating HPA axis dysregulation. Supported by Canadian Institutes of Health Research, and the Human Early Learning Partnership.