G.C.TAN1, D.CHIN2, A.TAN2, Y.X.S.TEY1, M.KEE3, H.Y.CHAN2, S.Q.CHOW2, Y.X.LOO2, M.J.MEANEY3
Institute of Mental Health1, National University of Singapore2, Agency for Science, Technology and Research (A*STAR)3
The CYP2D6 gene has been shown to be directly linked to anxiety and depression through neurotransmitter metabolism. We hypothesised that genetic estimates of brain CYP2D6 expression would be associated with lower anxiety and depressive scores in mothers and children given its importance in the regulation of neurotransmitters.
From a longitudinal cohort of children and their mothers from the GUSTO study, we first estimated CYP2D6 gene expression using PrediXcan and investigated an association with the Edinburgh Postnatal Depression Scale (EPDS) and/or State-Trait Anxiety Inventory (STAI) questionnaires in mothers and anxiety and depression in the Berkeley Puppet Interview in children. Separate bivariate correlation analyses were conducted to determine the relationships between CYP2D6 and EPDS/STAI scores at pregnancy week 26 in mothers and BPI in children aged 6. Backward linear regression models adjusted for age, ethnicity and population stratification were then obtained for these relationships.
Bivariate correlations revealed significant correlation between CYP2D6 expression and anxiety and depression in both children and mothers. Linear regression confirmed that mothers with higher CYP2D6 expression levels in frontal cortices have lower EPDS (β=-0.153; p-value = 0.002) and STAI scores (β = -0.100; p-value = 0.005). Childhood anxiety was predicted with higher expression of CYP2D6 in the amygdala (β=-0.124; p-value = 0.018), cortex (β=-0.133; p-value = 0.013) and frontal cortex (β=-0.128; p-value = 0.041).
Expression of CYP2D6 in frontolimbic regions appears to influence mood and anxiety symptoms in both children and their mothers and can be used as a potential personalized marker in the future.