Antenatal Maternal Anxiety is Related to HPA-Axis Dysregulation and Self-Reported Depressive Symptoms in Adolescence: A Prospective Study on the Fetal Origins of Depressed Mood

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Abstract
Depressive symptomatology can proceed from altered hypothalamic-pituitary-adrenocortex (HPA)-axis function. Some authors stress the role that early life stress (ELS) may play in the pathophysiology of depressive symptoms. However, the involvement of the HPA-axis in linking prenatal ELS with depressive symptoms has not been tested in a prospective-longitudinal study extending until after puberty in humans. Therefore, we examined whether antenatal maternal anxiety is associated with disturbances in HPA-axis regulation and whether the HPA-axis dysregulation mediates the association between antenatal maternal anxiety and depressive symptoms in post-pubertal adolescents. As part of a prospective-longitudinal study, we investigated maternal anxiety at 12–22, 23–32, and 32–40 weeks of pregnancy (wp) with the State Trait Anxiety Inventory (STAI). In the 14–15-year-old offspring (n=58) HPA-axis function was measured through establishing a saliva cortisol day-time profile. Depressive symptoms were measured with the Children's Depression symptoms Inventory (CDI). Results of regression analyses showed that antenatal exposure to maternal anxiety at 12–22 wp was in both sexes associated with a high, flattened cortisol day-time profile (P=0.0463) which, in female adolescents only, was associated with depressive symptoms (P=0.0077). All effects remained after controlling for maternal smoking, birth weight, obstetrical optimality, maternal postnatal anxiety and puberty phase. Our prospective study demonstrates, for the first time, the involvement of the HPA-axis in the link between antenatal maternal anxiety/prenatal ELS and depressive symptoms for post-pubertal female adolescents.