ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Neuroimage. 2019; 197:493–501. PMID: 31077842.

A large body of evidence suggests that the early environment can influence the health and wellbeing in children later in life. Variability in susceptibility to environmental stimuli might be mediated by interactions between genetic variations and the environment. The hypothalamic-pituitary adrenal (HPA) axis is the key biological stress response system, and dysregulation of this system is associated with depressive symptoms. Genes that are involved in HPA axis function and regulation are candidates to explain individual differences in sensitivity.

Here, Pozzi et al. investigated the associations between HPA-related genetic variation, maternal parenting behaviors and amygdala activity and connectivity during implicit emotion processing in a community sample of 80 children (46 girls, mean age: 10.0 years). Maternal behaviour was observed during mother-child interactions. Children underwent functional magnetic resonance imaging while performing an implicit emotion-processing task, and mothers and children completed measures of child internalizing symptoms. An HPA genetic risk score was calculated by combining 10 genotypes at 4 genes (FKBP5, CRHR1, NR3C2 and NRC31 ). The results showed that higher HPA genetic risk score was associated with greater amygdala-precuneus connectivity, which in turn was associated with greater child self-reported levels of depressive symptoms. The interaction between HPA genetic risk score and maternal negative behavior was associated with greater connectivity between the amygdala and the superior frontal gyrus, parietal operculum cortex, post-central gyrus and anterior cingulate cortex. Finally, the HPA genetic risk score neither alone nor in interaction with maternal parenting behavior was associated with amygdala reactivity.

Therefore, the authors demonstrated that genetic variation of the HPA axis directly, and in interaction with maternal negative parenting behavior, was associated with amygdala connectivity with regions involved in self-referential processing and emotion regulation, and may confer risk for depressive symptoms via an effect on these circuits. These findings further elucidate the complexity between gene and environment interaction in connection with early life environment and the HPA axis, and may help identify risk factors for the development of depression.